Guest guest Posted March 18, 2005 Report Share Posted March 18, 2005 Hi, everybody: I know this is slightly off topic but I am a Hashi's patient who is on Armour and also on progesterone cream. I posted this on another forum and didn't get one answer. I know there's some common sense out there and if anybody is willing to give me their thoughts on this, I'd sure appreciate it! " For some of you that don't know my history, I was diagnosed with lots of fibroids a couple months ago and have already had 2 lap. surgeries for pelvic pain and now face a third surgery. My doctor insists that fibroid tumors cannot cause pain but I've had lower back pain since December and a sharp pain at the top of my right leg for about 6 weeks. My last ultrasound indicates an enlarged, irregular, inhomogenous uterus and several fibroids, some embedded in the wall of the uterus. My question: if everything is enlarged and inflamed, isn't it possible that a fibroid or my uterus is pushing on a nerve or two? I want to ask people with common sense -- I know there is an abundance of it here, and often lacking in the medical community! " Thank you! ) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 18, 2005 Report Share Posted March 18, 2005 Of course it's possible, ! I had a gf with fibroids, she still has them, they keep coming back, but one was the size of a small baby it was sooo big. She looked pregnant. IF they are in the wrong place and large enough of course they cause pressure! Is the progesterone cream helping to shrink them at all? Nat > > Hi, everybody: > > I know this is slightly off topic but I am a Hashi's patient who is > on Armour and also on progesterone cream. I posted this on another > forum and didn't get one answer. I know there's some common sense > out there and if anybody is willing to give me their thoughts on > this, I'd sure appreciate it! > > " For some of you that don't know my history, I was diagnosed with > lots of fibroids a couple months ago and have already had 2 lap. > surgeries for pelvic pain and now face a third surgery. My doctor > insists that fibroid tumors cannot cause pain but I've had lower > back pain since December and a sharp pain at the top of my right leg > for about 6 weeks. My last ultrasound indicates an enlarged, > irregular, inhomogenous uterus and several fibroids, some embedded > in the wall of the uterus. My question: if everything is enlarged > and inflamed, isn't it possible that a fibroid or my uterus is > pushing on a nerve or two? I want to ask people with common sense - - > I know there is an abundance of it here, and often lacking in the > medical community! " > > Thank you! > ) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 18, 2005 Report Share Posted March 18, 2005 Of course it's possible, ! I had a gf with fibroids, she still has them, they keep coming back, but one was the size of a small baby it was sooo big. She looked pregnant. IF they are in the wrong place and large enough of course they cause pressure! Is the progesterone cream helping to shrink them at all? Nat > > Hi, everybody: > > I know this is slightly off topic but I am a Hashi's patient who is > on Armour and also on progesterone cream. I posted this on another > forum and didn't get one answer. I know there's some common sense > out there and if anybody is willing to give me their thoughts on > this, I'd sure appreciate it! > > " For some of you that don't know my history, I was diagnosed with > lots of fibroids a couple months ago and have already had 2 lap. > surgeries for pelvic pain and now face a third surgery. My doctor > insists that fibroid tumors cannot cause pain but I've had lower > back pain since December and a sharp pain at the top of my right leg > for about 6 weeks. My last ultrasound indicates an enlarged, > irregular, inhomogenous uterus and several fibroids, some embedded > in the wall of the uterus. My question: if everything is enlarged > and inflamed, isn't it possible that a fibroid or my uterus is > pushing on a nerve or two? I want to ask people with common sense - - > I know there is an abundance of it here, and often lacking in the > medical community! " > > Thank you! > ) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 18, 2005 Report Share Posted March 18, 2005 Of course it's possible, ! I had a gf with fibroids, she still has them, they keep coming back, but one was the size of a small baby it was sooo big. She looked pregnant. IF they are in the wrong place and large enough of course they cause pressure! Is the progesterone cream helping to shrink them at all? Nat > > Hi, everybody: > > I know this is slightly off topic but I am a Hashi's patient who is > on Armour and also on progesterone cream. I posted this on another > forum and didn't get one answer. I know there's some common sense > out there and if anybody is willing to give me their thoughts on > this, I'd sure appreciate it! > > " For some of you that don't know my history, I was diagnosed with > lots of fibroids a couple months ago and have already had 2 lap. > surgeries for pelvic pain and now face a third surgery. My doctor > insists that fibroid tumors cannot cause pain but I've had lower > back pain since December and a sharp pain at the top of my right leg > for about 6 weeks. My last ultrasound indicates an enlarged, > irregular, inhomogenous uterus and several fibroids, some embedded > in the wall of the uterus. My question: if everything is enlarged > and inflamed, isn't it possible that a fibroid or my uterus is > pushing on a nerve or two? I want to ask people with common sense - - > I know there is an abundance of it here, and often lacking in the > medical community! " > > Thank you! > ) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 18, 2005 Report Share Posted March 18, 2005 Thank you Nat, I'm only on my 3rd month of progesterone cream. I've had symptoms of estrogen dominance for AGES, and then I read Dr. Lee's wonderful book. This doc only discovered these fibroids in late January. She said I could have a 3rd surgery (oh joy) to have them removed, a myomectomy, or I could wait and come back in 6 months and have another ultrasound. I'm debating this all in my head, 'cause I've read prog. can shrink fibroids, but I'm sick of the pain. I just think she's crazy for saying there's no way they could cause pain! > > > > Hi, everybody: > > > > I know this is slightly off topic but I am a Hashi's patient who > is > > on Armour and also on progesterone cream. I posted this on > another > > forum and didn't get one answer. I know there's some common sense > > out there and if anybody is willing to give me their thoughts on > > this, I'd sure appreciate it! > > > > " For some of you that don't know my history, I was diagnosed with > > lots of fibroids a couple months ago and have already had 2 lap. > > surgeries for pelvic pain and now face a third surgery. My doctor > > insists that fibroid tumors cannot cause pain but I've had lower > > back pain since December and a sharp pain at the top of my right > leg > > for about 6 weeks. My last ultrasound indicates an enlarged, > > irregular, inhomogenous uterus and several fibroids, some embedded > > in the wall of the uterus. My question: if everything is enlarged > > and inflamed, isn't it possible that a fibroid or my uterus is > > pushing on a nerve or two? I want to ask people with common sense - > - > > I know there is an abundance of it here, and often lacking in the > > medical community! " > > > > Thank you! > > ) Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 18, 2005 Report Share Posted March 18, 2005 Since my story is kind of gross, hope you don't mind if I send it to yu personally. Gosh are doctors stupid or what. Sure fibroids can cause pain. I was on fibroid newsgroups for about 3 years and there was pain all over the place. First off they stretch and distort the uterus and pull the ligaments that hold the uterus and other organs in place. Then, if you've had two Laps, you might have some adhesions. They can definitely cause pain. Then, fibroids sometimes die and this will cause severe pain. (See Stanley West's " The Hysterectomy Hoax. " He talks about that.) I had them for over 6 years and they got huge, 20 week pregnancy. I had them all removed with mymectomy. But, because I was still an undiagnosed hypo, I grew two more small ones. Hypothyroidism causes the uterus to be highly sensitive to estrogen and causes high estrogen levels. Adrenal problems related to hypothyroidism seem to increase estrogen sensitivity in tissues. hypothyroidism also lowers immune function so you don't make natural killer cells that attack tumors. But, since I have been on 3-3/4 grains of Armour, they have stoped growing. I've had these for about 3 years. They can be quite uncomfortable depending on where they are located and their size. My big ones put pressure on my bowel and that was what drove me to surgery. I felt uncomfortable pressure and eventually they interfered with my bowel function and I was spending large amounts of time in the bathroom. One time back then, I developed a severe pain from one on the right side. I could hardly walk for two weeks. It was probably one that died. They are known to outgrow their blood supply and then they die and are reabsorbed. There is a lot of debate about progesterone cream and fibroids. The drug RU486 is being studied to shrink fibroids. It works by dropping progesterone levels to almost nothing. RU486 also raises natural killer cell levels and DHEA levels. I used progesterone cream for about two years while I had fibroids and It did not slow them down. I could not verify if it made them grow faster or not. It made me feel better, but the fibroids kept growing. The jury is really still out on progesterone. Dr. Lee says it will get rid of them, but I have not seen any reports of this happening on the newsgroups I was on. Some people think Uterine Fibroid Embolization is great, but while I was on the newsgroups, there was a disturbing number of reports starting to come in that this proceedure did not last and they would start to grow again. Then people were forced into myomectomies. But, the UFE proceedure left a lot of adhesions that made myomectomy difficult sometimes. In my book if you feel pain, then you have pain. Doesn't matter what doctors think. I ended up flying to Boston for surgery with a great doctor, Dr. Levine. Because mine were so big, hardly any regular doctor could do a myomectomy. Dr. Levine uses bloodless surgery and I did not need a blood transfusion for my surgery. But, I can't help but think that if I had had sufficient thyroid, I wuld have never needed surgery. Fibroids are very rare in well treated thyroid patients. Tish ____________________ Here are some sources related to fibroids and hypothyroidism. _______________________ " Thyroid, Guardian of Health " by Philip G. Young, MD, Trafford Publishing, , BC., Canada, 2002 But menstrual irregulaities are not the only hrmful affect low thryoid has on the uterus. A lack of thyroid greatly enhances the growth of uterine fibroids as well. If a woman is on sufficient amounts of thyroid the further growth of uterine fibroids usually will be blocked and frequently they will start shrinking. Besides uncontrolled bleeding, the major reason that women have hysterectomies is symptomatic uterine fibroids which can cause discomfort and contribute to excessive bleeding. Hypothyroidism also increases the incidence of uterine cancer which is the reason behind most the remaining hysterectomies. So thyroid has an almost magical impact on many of the woes associated with womanhood; it takes them away. (Page 117) And as mentioned elsewhere, there is a close relationship between the binding sites of thyroid and the binding sites of estrogen, so the function of thyroid and estrogen are intertwined in subtle ways. (Page 116) __________________________ " Hypothyroidism: The Unsuspected Illness " by Broda O. , M.D. and Lawrence Galton, Harper & Row, Publishers, New York, 1976 Fibroid tumors have been rare in hypothyroid women who have been maintained on adequate thyroid therapy. It is possible to produce fibroids in experimental animals by injection of estrogens, and there is evidence of excess of estrogens in hypothyroid women. In hypothyroidism, there is increased activity of the pituitary gland aimed at trying to stimulate the thyroid to produce more hormone secretions, and the increased pituitary activity may spill over to affect ovaries and increase their estrogen output. (Page 133) ________________ [Diagnosis of thyroid function in uterine myomatosis] [schilddrusenfunktionsdiagnostik bei Myomatosis uteri.] Zentralbl Gynakol 1989;111(1):47-52 (ISSN: 0044-4197) Lange R; Meinen K Gynakologisch-Geburtshilflichen Abteilung, St. Lukas Klinik Solingen. A correlation between thyroid disease and uterine myoma has been discussed till the fourth decade of this century. Since then, this possible connection was given no further notice. We examined 79 women needing a hysterectomy for various reasons regarding myometrial histology, thyroid function and thyroid antibodies. The patient group bearing myomas showed significantly more frequent (23%) pathological TRH/TSH stimulation tests results than the control group (3.7%, p = 0.0543). 10 of 22 patients with myomas had microsomal and/or thyroglobin antibodies, compared with none in the control group (n = 17, p = 0.0019). Therefore regarding these results a connection between thyroid disease and uterine myoma should undergo a more detailed examination. ______________________________ " The Great Thyroid Scandal and How to Survive It " by Dr. Barry Durrant-Peatfield MB BS LRCP MRCS, Barons Down Publishing, London, 2002, Part B - Oestrogen, Progesterone & Testosterone The hormones that keep us male and female are crucially affected by thyroid and adrenal function; and in turn can effect the proper functioning of the thyroid itself. So let us see where they fit in. Since my approach to metabolic problems is holistic, we have to ask if thyroid and adrenal insufficiency may be altered or worsened by deficiencies elsewhere. The answer is of course, yes. Since a state of lowered metabolism means that nothing really works as it was designed to, it follows that other hormone producing glands may not do their job properly either. It is a bit like an extraordinarily complex piece of electrical machinery, designed for 240 volts, running on 210 volts. It runs, but the lights look a bit dim and flicker a bit. Bringing up the voltage - gently - will get everything working again. So far as other components of the endocrine system go, we must be prepared for partial recovery only, and supplementation may well be indicated elsewhere as well. We are talking mostly about sex hormones here, and the effects of the menopause on both sexes. We have learnt already how important the adrenal corticosteroids are in the maintenance of the body's normal health; the male and female sex hormones, which are of course also steroids, are just as extraordinarily important in their own right. (It may have perhaps surprised you to realize that the whole body, most especially many of its hormones, is based on the steroid molecule. The use of the word " steroid " has been denigrated in the popular mind as being potentially, if not actually, dangerous, and this is a complete distortion. The contraceptive pill, for which millions of prescriptions are written weekly, is based on two steroids and few doctors and few patients are especially concerned that they do in fact belong to the great family of steroids). We will start with the female menopause, which will be hastened or worsened by a low thyroid/adrenal state. Literally, the menopause means " the last period " . For some women this is an abrupt thing, there one month and gone the next. Very often the process is rather more protracted than this; the periods start lengthening and sputter about; they may become heavy with pain and floods, or become very light and irregular. And menstrual problems, with heavy irregular periods, are certainly associated with low thyroid. So we need to have a look at the whole business, so that we can decide to intervene if necessary while treating the metabolic problems. Women actually produce three different sex hormones, oestrogen (which has three different forms: oestradiol, oestrone and oestriol), progesterone and testosterone. You thought testosterone was a male hormone, didn't you. Well, it is; but women produce it too - though less than men of course. (The reverse is also the case.) In general oestradiol, the main oestrogen, comes from the ovaries, the other two from the adrenals, directly or indirectly, and more after the menopause. The way it all works is this. As the menarche (the start of periods) approaches, the ovaries start to produce oestrogen and under the influence of a pituitary hormone, the Follicle Stimulating Hormone (FSH), an ovarian follicle (of which there are many hundreds containing egg cells waiting their time) matures an ovum which surfaces about mid cycle and is released. It finds its way into one of the fallopian tubes (right or left, depending on which ovary produced the ovum) where it may or may not be fertilized. The place from where it was released on the ovary undergoes a change to produce the Corpus Luteum or " Yellow Body " . This structure begins to produce under the influence of Luteinizing Hormone (LH) from the pituitary, another hormone, progesterone. This prepares the lining of the womb for implantation if the ovum is fertilized. Oestrogen and progesterone are produced together for the second half of the cycle; and then the supply is cut off abruptly which starts off the menstrual period. Hypothyroidism can affect this process in several ways. To start with, a low thyroid state affects the onset of the first period, oddly enough in two opposing ways. The first period may come unusually early at 8, 9 or 10 years old; or, it may come unusually late, 15, 16 or 17 years old. Periods starting abnormally like this should raise a suspicion about the thyroid at once. The periods may be abnormal in other ways. They may be exceedingly painful with collapse and prostration of the unfortunate girl; they may be very heavy or very light or come at irregular times. There may be premenstrual tension to make life miserable. These problems may occur at any time of life, but may sort themselves out a bit after having children. Then in the later thirties and early forties it all goes wrong and flooding and terrible PMT may ruin things so badly that relationships suffer. The gynecologist may not think of thyroid dysfunction as a cause and the ladies then become the target of various synthetic hormone combinations, which may or may not bring relief. It is at this point, of course, that hysterectomy becomes the treatment choice, and worn out with it all, the unhappy sufferer consents to surgery. Relief from the terrible periods may well justify the hysterectomy for the patient; but it may have missed the point altogether. As I said earlier, hysterectomy is very likely to affect thyroid activity. There seems to be a chemical dialogue between the womb and the thyroid; and interference - including sterilization, termination, or even a D&C, seems to damage thyroid function for many. The weight gain, which nearly always occurs, is not due to comfort eating while grieving for one's lost fertility, but because thyroid activity may be further damaged. This, and the other symptoms of a running down of thyroid activity, is a heavy price to pay for an operation for which one out of every three, at least, wasn't necessary and could have been avoided if thyroid status had been properly assessed and treated. The other worry which besets women at this time of their lives is premenstrual tension (PMT) or as the Americans call it (PMS) premenstrual syndrome. Some doctors won't have that this occurs at all. I remember reading an authoritative article by a lady doctor who discounted it completely; one just wonders what planet she came from. Not only is it a very real problem; if anything it is getting worse. Although a number of causes have been cited, it seems clear that it is associated with an imbalance between the oestrogen and progesterone production. This last, may drop anyway with the general loss of viability of the ovum and the corpus luteum; but it is much worse with deficient thyroid hormone. Throughout my experience with low thyroid, I have been staggered to find that some women lose their PMT within a month or so of starting their thyroid supplementation - simply the result of improved progesterone production. Where progesterone production in the mid thirties and forties has not been improved by thyroid supplementation, very thoughtful consideration must be given to the provision of progesterone supplementation. The standard way of doing this is by the use of a group of artificial progesterones, which are called progestogens and the synthetic hormone Norithesterone is an example. While these may well be helpful for some women, they have a number of side effects which have made them less and less popular; nevertheless, an alternative must be sought. As oestrogen dominance brings with it its own problems of bloating, weight gain and increased risk of cancer, a progesterone supplementation is essential. Of increasing popularity nowadays is the use of natural progesterone, which is actually extracted from plants and is incorporated in creams which may be simply rubbed into the skin daily. Although establishment thinking is, as might be expected, somewhat suspicious of the natural product, favoring the artificial, very many thousands of women are greatly benefiting from transdermal progesterone (see Appendix D). Another worrying result of a reduction in thyroid function is a reduction of red blood cell production; many people are troubled by a refractory anaemia (when it is unresponsive to treatment), which adds to their general lack of well-being and exhaustion. How much worse is it then, when heavy prolonged periods are added to the problem.. . Iron, folic acid and vitamin C would seem to be essential, especially in the early phases of treatment. A most alarming gap in the management of infertility, is the failure to realize that a prime and a gravely neglected cause is hypothyroidism. It is obvious that there are several ways the healthy ovum can be affected: its production, its maturation, proper fertilization and implantation....... (Pages 135 - 139) ___________________________ Ginecol Obstet Mex. 1969 Dec;26(158):777-85. [Report on the relation between limited hypothyroidism and uterine fibromyomatosis] [Article in Spanish] Gutierrez JT. PMID: 5408031 [PubMed - indexed for MEDLINE (Paper can be purchased from PubMed) _____________________ Akush Ginekol (Mosk). 1988 May;(5):46-50. [The reproductive system of patients with disordered thyroid function] [Article in Russian] Sosnova EA. PMID: 3177773 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ___________________________ J Assoc Physicians India. 1993 Feb;41(2):88-90. Comment in: J Assoc Physicians India. 1993 Nov;41(11):761-2. Hypothyroidism presenting with polycystic ovary syndrome. Sridhar GR, Nagamani G. Endocrine & Diabetes Centre, Visakhapatnam. During a 30 months period, two women of primary hypothyroidism (2/13; 1.04%) presented with features of polycystic ovary syndrome (PCOS). In hypothyroidism, sex hormone binding globulin levels are decreased; increased conversion of androstenedione to testosterone, and aromatization to estradiol are present, all these being an exaggeration of biochemical changes characteristic of PCOS. Besides, metabolic clearance rates of androstenedione and estrone, the putative mediators of PCOS, are reduced. Hypothyroidism can either initiate, maintain or worsen the syndrome. Correction of hypothyroidism when present, would therefore form an important aspect in the management of infertility associated with PCOS. Publication Types: Case Reports PMID: 8053991 [PubMed - indexed for MEDLINE] __________________ Pediatr Akus Ginekol. 1968 Sep-Oct;5:55-8. [Function of thyroid gland in uterine fibromyoma] [Article in Ukrainian] Sol's'kii IaP, Chizhova PS, Ivaniuta PI. PMID: 5743398 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _______________________ Akush Ginekol (Mosk). 1970 Oct;46(10):24-7. [Functional status of the thyroid gland in patients with uterine myoma] [Article in Russian] Vasilevskaia LN, Kotliarov EV. PMID: 5519731 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _________________ Ginecol Obstet Mex. 1974 Jun;35(212):657-80. [Edocrinal study of uterine fibromyoma] [Article in Spanish] Nava y R. PMID: 4138171 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ____________________ Akush Ginekol (Mosk). 1967 Oct;43(9):17-21. [Adrenal cortex and thyroid gland function in patients with myoma of uterus] [Article in Russian] Slepov MI, Novouspenskaia IE. PMID: 5607969 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ________________ Author: GRIFF T. ROSS, M.D., Date Published: 01-Jan-1958 Publication: Journal of Clinical Endocrinology and Metabolism 18: 492-500, 1958 Title: SEVERE UTERINE BLEEDING AND DEGENERATIVE SKELETAL-MUSCLE CHANGES IN UNRECOGNIZED MYXEDEMA Category: reproductive Keywords: reproductive, problem, ROSS, SEVERE, UTERINE, BLEED, DEGENERATIVE, SKELETAL, MUSCLE, CHANGE, UNRECOGNIZED, MYXEDEMA, treat, women, menstruation, severe, anemia, normal, desiccated, thyroid Text: p 492 ABSTRACT Two cases of severe uterine bleedng associated with unrecognized myxedema (hypothyroidism) are reported. Degenerative changes in skeletal muscles were suggested by the results of electromyographic studies and demonstrated by biopsy of a muscle prior to treatment in one patient. The uterine bleeding stopped promptly and a normal menstrual cycle was re-established in both patients after treatment with desiccated thyroid. DISTURBANCES in thyroidal function in premenopausal women are often associated with abnormalities of menstruation. Either menorrhagia or amenorrhea may develop in patients with spontaneous or postoperative myxedema. However, when amenorrhea occurs in a premenopausal women with the secondary hypothyroidism the diagnosis of hypopituitarism should be considered and excluded. In his book, Means stated: " Menorrhagia may be sufficiently impressive in ordinary myxedema so that in several cases that have come to our attention patients have actually had a dilation and curettage for it when all they needed was desiccated thyroid for treatment. " We are reporting 2 cases of profuse uterine bleeding with severe anemia secondary to unrecognised primary myxedema, in which prompt cessation of uterine bleeding and restoration of normal menstrual cycles followed the oral administration of desiccated thyroid. Significant degenerative changes in the skeletal muscles were suggested by the results of electromyography and were demonstrated by muscle biopsy prior to treatment in one of these patients. p 494 .. ....COMMENT Both these patients were referred for consideration of surgical treatment for intractable profuse uterine bleeding. Severe menorrhagia lasting from p495 six to ten days had been present during the six months preceding the admission of the first patient to the hospital. After the clinical recognition of myxedema, it was realized that the bleeding might be due to the hypothyroidism. For this reason, operation was deferred until the patient could be restored to euthyroid state. After five days of oral treatment with desiccated thyroid, the uterine bleeding ceased. The menstrual pattern subsequently returned to normal with regard to periodicity and flow. Despite the fact that the second patient had noted intermenstrual spotting for many years, the myxedema in all probability began after her last pregnancy in 1950. There was nothing to suggest anterior- pituitary insufficiency, since the patient lactated and cyclic menstrual periods were re-established following parturition. She was extremely exsanguinated on admission, as shown by the clinical picture of mild shock and severe anemia. Her response toe desiccated thyroid was most gratifying, since the uterine bleeding stopped after seven days of therapy. A checkup after three months off treatment revealed that she was clinically euthyroid. A remarkable change had taken place in the facies (Fig. 1). normal menses had returned. __________________ Author: JENNINGS C. LITZENBERG, M.D. Date Published: 01-Jan-1937 Publication: JAMA, 109:1871-1873, 1937 Title: THE ENDOCRINES IN RELATION TO STERILITY AND ABORTION Category: reproductive Keywords: reproductive, problem, LITZENBERG, ENDOCRINE, RELATION, STERILITY, ABORTION, fertile, pregnancy, develop, hormone, fetus, basal, metabolic, rate, menstrual, thyroid, women, normal Text: p1871 The endocrines govern the physiology of reproduction from beginning to end; spermatogenesis, ovogenesis, maturation of the ovum, ovulation, fertilization, preparation of the endometrium for nidation, implantation of the fertilized ovum, placentation, maintenance of pregnancy, development of the fetus, birth and lactation - all are dependent on hormones initiated and controlled by the anterior hypophysis. p1872 .....THE THYROID AND STERILITY Since 1922 I have studied the relation of the basal metabolic rate to sterility, abortions, and menstrual disturbances. In our first small series of sixty-nine consecutive sterile women, in whom no other evidence of myxedema was present, 50 per cent had a low basal rate; adding those who had conceived but aborted the figure was 56 per cent. Carefully supervised thyroid medication resulted in 33.3 per cent conception, 14 per cent of whom aborted. One woman conceived three times under thyroid medication, bringing the percentage of conceptions to 40. In another group of 114 women, 45 per cent of the married women were sterile and 40 per cent of the entire group had functional disturbances of menstruation. In a second series of 137 women, approximately the same figures were obtained, but in addition we found that 63 per cent had abnormal menses (our patients all came from a goiter area). Our third series (including the pervious reports) consists of 255 married women, 49.7 per cent of whom were sterile. Of 332 women, married and unmarried, 33.5 per cent had functional disturbances of menstruation. During the fifteen years of our experience to date (including cases not previously reported) there was a consistent rate of conceptions of 30 per cent in women with low basal rates. Haines and Mussey of the Mayo Clinic confirmed our thyroid treatment of functional menstrual disturbances, saying: " Because of a desire to determine the effectiveness of thyroid medication alone, in the treatment of certain menstrual disturbances, no patient received any other treatment. All were definitely improved; amenorrhea, 72 per cent; oligomenorrhea, 55 per cent; menorrhagia, 73 per cent, and general health, 75 per cent. " Also in this connection Haskins says: " Most gynecologists agree that thus far, of all the gland products, thyroid has proved to be the most useful for a variety of endocrine disturbances, including amenorrhea, oligomenorrhea, menorrhagia, sterility and abortion. " Marine, long ago (1917) when there was scarcely any usable knowledge of the endocrines, declared: " The relation of the thyroid to the sex organs in the female is the most frequent and classical illustration of the interrelation of the function of glands with internal secretions. " adds testimony by saying " The sole endocrine preparation that has proved itself of real value has been thyroid extract, which is of use in patients with lowered basal metabolism. " Novak declared that thyroid medication in sterility and abortion are more often efficacious than any other form of organotherapy. Desiccated thyroid was the first, and is still one of the few successful, substitutional hormone preparations. Perhaps when one gives desiccated thyroid one is doing to the ovaries what the pituitary has failed to do through stimulation of the thyroid gland by means of the thyrotropic hormone. I quote the concluding paragraph of an editorial in THE JOURNAL: These reflections [criticisms of the misuse of sex gland hormones] are not intended to inhibit chemical and biologic studies in accredited laboratories. Neither do they apply to the carefully controlled clinical application of accepted knowledge by competent observers; this is necessary. Rather are they intended (1) to emphasize that there is a great discrepancy between laboratory knowledge of the hormones and their clinical application, (2) to suggest that for the present only those clinicians with facilities for critical study be encouraged to administer the newer endocrine preparations to patients and that these clinicians be urged to publish their negative as well as their positive results, and (3) to suggest that a large group of physicians not represented in either of the groups mentioned cease their undiscriminating injection of unknown substances into unsuspecting patients. Physicians are perhaps cynical because of our limited knowledge of the endocrines and the complexity that faces it, but the tendency is to optimism when it contemplates the accomplishments of the recent past with their great promise for the future. _____________________ Author: RUTH C. FOSTER Date Published: 01-Jan-1939 Publication: ENDOCRINOLOGY 24:383,1939 Title: THYROID IN THE TREATMENT OF MENSTRUAL IRREGULARITIES Category: reproductive Keywords: reproductive, problem, FOSTER, THYROID, TREAT, MENSTRUAL, IRREGULAR, women, period, basal, metabolic, pelvis, metrorrhagia, amenorrhea, bleed, relief, continue, normal, desiccated Text: p383 DURING THE PAST few years we have been impressed by the efficacy of thyroid medication in the treatment of menstrual irregularities. Because our series of cases has shown results similar to those reported by clinicians working elsewhere, it has seemed worth while to summarize our data and present it in confirmation of material published previously. Fifty cases treated with thyroid have been observed for a period of from one to four years. These patients have been seen at least twice a month. Their ages have ranged from 16 to 34, although 41 of the series have been under 22 years of age. All have had complete physical examinations, pelvic studies, and repeated basal metabolic determinations. With a few exceptions, which will be discussed later, only those who showed no pathology in the pelvis have been treated with thyroid. .....Among this group of patients 25 complained of dysmenorrhea which was of sufficient severity to cause repeated absence from classes. Seventeen complained of scanty or delayed menstrual periods with intervals of as long as three months. Thirteen complained of too frequent periods or of inter-menstrual bleeding, while 7 had excessive flow together with the metrorrhagia. There were 5 cases of amenorrhea which was of 7 months to 4 years duration. Four of the patients had normal periods but there was a marked irritability with inability to concentrate for as long as a week prior to the period. p385 Of the 17 cases of oligomenorrhea, all reported definite relief as long as they continued taking thyroid. Several of this group tried going without therapy during the summer vacation but returned in the fall asking to resume treatment because their symptoms had recurred. All stated they felt much better when having their regular periods. .....The group of patients who complained of amenorrhea is small due to the fact that pathology was found to explain the cessation of periods in many of those who had this complaint. Those patients treated were given thyroid because their B.M.R. were low, and they or their parents wished them to receive a trial with thyroid before endometrial biopsies and further studies were made. p386 Those patients complaining of menorrhagia and metrorrhagia responded to thyroid therapy in a most satisfactory manner. The one failure was in a patient who had a large ovarian cyst removed because of prolonged menorrhagia. .....V.C., a university junior 18 years of age, consulted the Student Health Department because of a slight menstrual flow of six weeks duration, early fatigue, and a tendency towards a rapid gain in weight. She stated that her menstrual periods began when she was 13 and that they had always been irregular, occurring at intervals of three weeks to several months (9 months at one time). .....Treatment consisted of 1 to 2 gr. desiccated thyroid daily. The B.M.R. rose to -5, blood pressure to 108/78; the bleeding stopped and apparently normal periods occurred until the dose of thyroid was reduced, when there was a recurrence of the metrorrhagia. This patient has learned that she will have no symptoms I she takes thyroid in sufficient dosage to keep her B.M.R. -5 or above. This has been so consistent in her case that she can accurately predict her B.M.R. will be below these levels when the metrorrhagia recurs. p387 Four patients who complained of marked irritability prior to their periods are included in this series because their complaint was enough to interfere with their ordinary activities, and 3 did have relief with thyroid. Two noted partial relief, enough so that they did not want to stop thyroid medication. One had complete relief and one noted no difference. Thyroid was stopped several times but always with a recurrence of their symptoms. ..... DISCUSSION The explanation for the efficacy of thyroid medication in these cases can only be hypothesized. Experimental work in animals has shown that ablation of the thyroid is followed by an increase in size of the pituitary gland. Microscopic examination of these pituitaries shows hydropic degeneration, which explains the fact that after this procedure glands lose some of their potency. It may follow that in these patients there is an inadequate thyroid secretion resulting in a decrease in potency of the pituitary gland, which in turn causes inadequate gonad stimulation. One might go farther and state that the 4 patients who noted breast engorgement for the first time were having their first normal cycles with luteinization occurring. p388 Some of these problems may be solved by a study of endometrial biopsies before and after treatment. In a group of patients as young as these reported, most of whom are minors, it is difficult to obtain permission for biopsies from the parent, but as the public becomes educated to this procedure more parents should be willing to consent. It is our feeling that a B.M.R. should be obtained in all cases complaining of menstrual irregularities such as those reported above. Providing there is no pelvic pathology or physical condition to explain the symptoms, these patients should probably receive a trial with thyroid before further therapy is undertaken if their metabolic rates are below zero. It is understood that these patients will report periodically to their physicians and that the dose of thyroid will depend upon the individual response. In many cases there will be a complete relief of symptoms with small doses of thyroid although the metabolic rate has not reached what is considered the normal level. There is no way of predicting from the individual B.M.R. the degree of relief to be obtained. SUMMARY Fifty patients with ages ranging from 16 to 34 years were seen because of dysmenorrhea, oligomenorrhea, amenorrhea, metrorrhagia and menorrhagia. All were apparently healthy individuals with normal pelvic findings. These patients had B.M.R. ranging from -1 to -33 with an average of -15. All were treated with desiccated thyroid. Of 25 cases of dysmenorrhea 17 had complete relief, 5 partial, and 3 no relief. Of 4 patients with amenorrhea lasting from 8 months to 4 years only one had relief of her symptoms. Among 13 patients with metrorrhagia 12 had complete relief and of 7 with a menorrhagia 6 had complete relief. It is suggested that a B.M.R. should be determined in those individuals complaining of menstrual irregularities who have no demonstrable pathology to explain their symptoms. A therapeutic trial of thyroid is indicated if the B.M.R. is zero or below. ______________________ Author: BRODA O. BARNES M.D Date Published: 01-Jan-1949 Publication: MEDICINE January, 1949, Vol. 6, No. 1 pp. 33-34 Title: THE TREATMENT OF MENSTRUAL DISORDERS IN GENERAL PRACTISE Category: reproductive Keywords: reproductive, problem, BARNES, TREAT, MENSTRUAL, DISORDER, GENERAL, PRACTISE, thyroid, therapy, improve, patient, Basal, Temperature, relieve, bleed, women Text: The general practitioner can expect about 10 per cent of his patients to complain of menstrual difficulties. .....In 1939 and Thornton reported 50 cases of menstrual irregularities treated with thyroid therapy. Their results were far better than any published before or since. This present report of 143 cases is presented in confirmation of their work, and outlines an inexpensive plan of management which produces gratifying results. .....Control series for a group of cases of this kind are difficult. Each case serves as its own control for the period before therapy. Many of the patients relieved of their symptoms ceased medication and in a few months would have a return of their previous complaints. Thyroid therapy would again correct their menstrual difficulty. In view of the fact that the number of patients who were improved in the present series is almost identical, in proportion, with that of and Thornton in 1939, it seems reasonable to assume that the results are due to the treatment. SUMMARY One hundred forty-three cases of functional menstrual disorders have been studied. Dysmenorrhea, excessive bleeding and irregular menstrual cycles are included. The Basal Temperature usually is subnormal. Thyroid therapy relieves the symptoms in about 90 per cent of these cases. _______________________ Author: JOSEPH C. SCOTT, JR., M.D. Date Published: 01-Jan-1965 Publication: American Journal Obstetrics and Gynecology 90:161-165, 1965 Title: Menstrual patterns in myxedema Category: reproductive Keywords: reproductive, hypo, problem, pattern, myxedema, SCOTT, hypo, gland, menstruation, mild, test, menstrual, thyroid, hormone, menorrhagia, disease Text: 161 HYPOFUNCTION of the thyroid gland produces a broad spectrum of symptoms and signs, often including a change in the menstrual pattern. The various disorders of menstruation which may be associated with myxedema have been documented, but a difference exists in the reported frequency and types of abnormal menstrual pattern. Hypothyroidism has been implicated as the underlying cause of many irregularities of menstruation. .....Generally, it is believed that thyroid hormone is beneficial and its use is indicated only when there is evidence of thyroid hypofunction. A patient may be considered to be mildly hypothyroid by one clinician and euthyroid by another on the basis of only a single interview or test. No single test or procedure will define the status of the thyroid gland. Furthermore, any combination of methods may lead to erroneous interpretation or to inconsistent results. The clinician must have the faculty of correlating the clinical appearance of the patient with the laboratory findings. p 164 .....Comment Menorrhagia, that is, an increase in the amount and duration of menstrual flow, associated with myxedema may be mild, " occult, " or severe. Mild menorrhagia is a source of only minor concern and usually is corrected by better control of the myxedematous state. The term " occult menorrhagia " is warranted in cases in which there is excessive or prolonged menstruation which the patient considers to be normal. In these cases the onset of the menorrhagia has been so insidious that the patient is truly unaware of the change unless questioned closely (Case 2). Severe menorrhagia may require diagnostic curettage in addition to thyroid replacement therapy. Thyroid dysfunction should be considered in evaluation of each case of menstrual irregularity. Our studies reinforce the observations of other authors that menstrual disorders are not unusual in myxedema. A careful gynecologic examination should be performed for each patient suspected of having a thyroid disease. Any menstrual disorder should not be minimized and the possibility of genital malignant disease should be considered. Laboratory studies have greatly aided the clinicians in defining and evaluating thyroid disease states, but the " clinical appearance " of the patient should continue to be a prime factor in evaluation. Diagnostic measures, such as the quantitation of menstrual blood loss by tagging with radioactive chromium, are useful and informative in many patients, but not indispensable. Menorrhagia is the most frequent of the menstrual aberrations which are associated with myxedema. Hypomenorrhea and amenorrhea are much less common, and we have found oligomenorrhea to be rare. p 165 Summary The menstrual patterns of 50 premenopausal myxedematous women between 16 and 40 years of age were evaluated. Abnormal menstrual patterns occurred in 56 per cent of these patients. More than one form of menstrual irregularity was noted in two cases. Menorrhagia and metrorrhagia, alone or combined, constituted the abnormal patterns in 75 per cent of the patients. Amenorrhea occurs infrequently with myxedema. " Occult " menorrhagia should be considered in the evaluation of the patient with thyroid disease. _______________________ Author: Longcope Date Published: 30-Jun-1996 Publication: Werner and lngbar's The Thyroid, Seventh Edition, edited by E. Bravennan and D. Utiger. Lippincott-~ven Publishers, Philadelphia, @ 1996 Title: 71 The Male and Female Reproductive Systems in Hypothyroidism Category: reproductive Keywords: Longcope, reproduction, uterus, ovaries, hypo, thyroid, endometrial, muscle, animal, human, fertility, sexual, vagina, precocious, puberty, fetal, abort, testicular, sperm, libido Text: 849 HYPOTHYROIDISM IN THE FEMALE REPRODUCTIVE SYSTEM Hypothyroidism seems to affect the reproductive system in women more than in men. A review of the normal develop- ment and physiology of the female reproductive system has been given in chapter 47. Animal Studies In sheep, fetal hypothyroidism does not affect reproductive tract development but does result in prolonged gestation despite maternal euthyroidism.l However, in the rat, fetal hypothyroidism results in small ovaries deficient in lipid and cholesterol.2 Thyroidectomy of sexually immature rats results in delayed vaginal opening and sexual maturation; smaller ovaries and follicles than in controls3,4; and uteri and vaginas that are not well developed.5 When adult female rats are rendered hypothyroid their estrous cycles become irregular and their ovaries become atrophic.6 There is an enhanced response to HCG with the development of large cystic ovaries in hypothyroid rats.7 Hypothyroidism in hamsters and cows is associated with abnormal estrous cycles,s.9 and in hypothyroid hens there is a decrease in egg production.9 In the mature female rat, hypothyroidism apparently does not result in sterility but does interfere with gestation, especially in the fIrst half of pregnancy,lO with resorption of the embryo and subsequent reduction in litter size and an increase in stillbirths.ll In hypothyroid sheep, the uterus shows endometrial hyperplasia and smooth muscle hypertrophy, perhaps related to the prolonged estrous noted in hypothyroid ewes.12 Ruh and coworkers 13 reported increased estradiol binding in uteri of hypothyroid rats, but Kirkland and coworkers 14 found a decrease in the uterine response to estrogen in hypothyroid rats. Hypothyroidism inhibits the photoperiod responses and seasonal breeding patterns in sheep and birds.15,16 Human Studies and Clinical Aspects The reproductive tract appears to develop normally in cretins; thus, hypothyroidism during fetal life does not appear to affect the normal .development of the reproductive tract. Hypothyroidism in prepubertal years generally leads to short stature and may lead to a delay in sexual maturity.4 However, an interesting syndrome described by Kendlell and Van Wyk and Grumbach 18 occurs not infrequently: it is characterized by precocious menstruation, galactorrhea, and sella enlargement in girls with juvenile hypothyroidism. The cause is thought to be an overlap in the pituitary production of TSH and gonadotropins, with the latter causing early ovarian secretion of estrogens and subsequent endometrial stimulation with vaginal bleeding. Prolactin levels are elevated, leading to galactorrhea. However, there is no pubertal increase in the adrenal production of androgen precursors, so that axillary and pubic hair are usually not apparent.I8 Therapy with thyroxine in proper dosage results in prompt alleviation of the symptomatology. In adult women, hypothyroidism results in changes in cycle length and amount of bleeding I9-21 and has been reported 850 in association with the ovarian hyperstimulation syndrome.22 Menorrhagia is a frequent complaint and is probably due to estrogen breakthrough bleeding secondary to anovulation, which is frequent in severe hypothyroidism. 19 The anovulation is reflected in the frequent finding of a proliferative endometrium on endometrial biopsy.23 TRa-l and TRBB-1 receptors have been found in human granulosa cells and both triiodothyronine and thyroxine have been found in follicular fluid.24 Earlier work in- dicated that thyroxine enhanced the action of gonadotropins on luteinization and progestin secretion by cultured granulosa cells,25 and it has recently been noted that in a group of infertile women, those with elevated TSH levels had a higher incidence of out-of-phase biopsies than women with normal TSH.26 Ovulation and conception can occur in mild hypothyroidism, but in the past those pregnancies that did occur were often associated with abortions in the first trimester, stillbirths, or prematurity, 19,27 Recent studies indicate these events may be less common but that gestational hypertension occurs often in pregnant women with untreated hypothyroidism.28 Pregnancy occurring in women with myxedema has been reported to be uncommon,27 but this is somewhat hard to document and may be the result of anovulation. The use of L-thyroxine is not helpful in treating euthyroid patients for infertility, menstrual irregularity, or the premenstrual syndrome.29,30 In evaluating the thyroid status of the pregnant woman, the level of TSH is probably the best indicator of changes in thyroid function. Because radioiodine will readily cross the placenta and can cause fetal hypothyroidism, tests involving ra- dioiodine administration to the mother are contraindicated in pregnancy.19 When hypothyroidism is diagnosed during pregnancy, L-thyroxine therapy should be instituted promptly to increase the chances for a normal pregnancy. Although it has been thought that little L-thyroxine would cross the placenta,19 it appears that L-thyroxine will cross the placenta in modest amounts,31 at least early in pregnancy. Women who have required thyroid hormone therapy prior to pregnancy should continue with such therapy throughout the pregnancy. How- ever, recent evidence indicates that the hormone dose needs to be increased during pregnancy, even though adequate replacement had been given before conception.31 It is advisable to monitor the serum TSH concentration at least once during each trimester to ensure that an adequate dose is received. Thyroid disease during and after pregnancy is discussed in detail in chapter 89. Some myxedematous women will present with amenorrhea and galactorrhea and elevated serum prolactin concentrations.19 Thus, thyroid evaluation should be an essential part of the work-up in any person with galactorrhea. If hypothyroidism is the cause, the amenorrhea and galactorrhea and elevated serum prolactin will disappear promptly with thyroxine therapy.32 There is an increased incidence of Hashimoto's thyroiditis in individuals with 's syndrome,33 and, although a chromosomal linkage between autoimmtme disease and the X- chromosome has been suggested, this has not been confirmed.34 Inherited abnormalities in serum thyroxine-binding globulin (TBG) are X-linked, and patients with 's syndrome may ,have low serum TBG values.35 Women with hypothyroidism have decreased metabolic clearance rates of androstenedione and estrone and increased peripheral aromatization.36 The ratio of 5a/5B metabolites of androgens is decreased in hypothyroid women, and there is an increase in the excretion of estriol and a decrease in the excretion of 2-oxygenated estrogens.37 In summary, hypothyroidism in girls can cause alterations in the pubertal process; this is usually a delay, but occasionally it can result in pseudoprecocious puberty. In mature women, hypothyroidism usually is associated with abnormal menstrual cycles, especially anovulatory cycles, and an increase in fetal wastage. HYPOTHYROIDISM IN THE MALE EPRODUCTIVE SYSTEM The normal development and physiology of the male reproductive system has been described in chapter 47. Although less common in men than in women, hypothyroidism, induced or spontaneous, affects the male reproductive tract in a number of ways depending, in part, on the age of onset. Animal Studies The fetal thyroid starts functioning about the same time as the gonads.38 Although thyroid hormones play role in sex differentiation and gonadal maturation in fish and amphibians,39 they do not appear to be necessary for the normal development of the reproductive tract in mammals. 1 However, hypothyroidism, induced or occurring soon after birth, is associated with a marked delay in sexual maturation and development.40 When rats are made hypothyroid with propylthiouracil administered from birth to 24 to 26 days of age, testicular size is decreased, Sertoli cell differentiation is retarded, and the time of Sertoli cell proliferation is prolonged.4].42 As these rats become older and euthyroid, then the testis size, Sertoli cell number, and sperm production are all increased.41, Leydig cell numbers are increased but testosterone secretion per cell is decreased, although total testosterone secretion remains the same as controls.43 FSH and LH levels tend to remain low throughout treatment and recovery periods, whereas inhibin levels are elevated.41 However, if hypothyroidism persists untreated, there is an arrest of sexual maturity with absent libido and ejaculate.44 The interstitial cells of the testis are reduced in number and the arrested growth of the accessory male sex organs indicates a decrease in the production of testosterone.44 The longer the hypothyroidism persists, the greater the degree of damage to the testes,44 although genetically induced hypothyroidism in male mice is associated with normal fertility .45 In the adult ram, hypothyroidism is associated widl a decrease in testosterone concentration but normal spermatogenesis.46 In the mature male rat, the induction of hypothyroidism has little effect on the pathology of the testes, sperlllatogenesis, or serum testos- terone concentrations.47 Thus, it would appear that hypothyroidism can affect the immature, but not the mature, testis. Human Studies and Clinical Aspects The development of hypothyroidism in the male fetus does not appear to affect the reproductive system. Cretins are usually born with a normally developed reproductive tract. The presence of hypothyroidism in the prepubescent years usually results in a delay of sexual maturation and of the whole pre-pubertal process, which can be overcome by the administration of adequate doses of thyroxine. However, in some instances, hypothyroidism can result in precocious pseudopuberty marked by the early development of external genitalia, but without the appearance of axillary and pubic hair. 48 This syndrome probably results from an increased secretion of gonadotropins along with TSH from the enlarged pituitary.48 In men, hypothyroidism has been suggested as a cause of infertility,49 but there is considerable disagreement with this suggestion. 50 If an infertile man is found to be hypothyroid, one should suspect secondary hypothyroidism and pituitary disease rather than primary myxedema, and there is no reason to treat infertile euthyroid men with thyroid hormone.50 In hypothyroid men, testicular size and potency may be normal and, despite early reports of defective spermatogenesis in hypothyroidism, 51 semen analysis is usually normal.52 Wortsman and colleagues reported that myxedema was often associated with infertility and impotence, but in this report the impotence did not improve when the men became euthyroid.49 In addition, there was a decrease in serum testosterone and free testosterone and, in the men who were not over-weight, an increase in sex hormone-binding globulin. It should be noted that sex hormone-binding globulin levels have also been reported as both decreased53 and normal 54 in hypothyroid men. Many men with hypothyroidism do note a decrease in libido, but this is probably a nonspecific disease-related complaint, which disappears when the euthyroid state is achieved with thyroid replacement therapy. Variations in testis size and histology have been noted in autopsy material,55,56 and De La BaIze and coworkers 51 noted Leydig cell hyperplasia and tubular hyalinization. There is a marked decrease in the 5a/5B ratio of the metabolites of androstenedione and testosterone, which is the reverse of that seen in hyperthyroidism 57 In summary, although hypothyroidism in boys frequently interferes with the normal pubertal process, the development of hypothyroidism in men has a less clear-cut effect on the reproductive system. References - not thoroughly checked 1. Hopkins PS, Thorburn GD. The effects of foetal thyroidectomy on the devel2. Leathem JH. Extragonadal factors in reproduction. In: Lloyd CW, ed. Recent progress in the endocrinology of reproduction. New York: Academic Press, 1959:179 3. Leathem]H. Role of the thyroid. In: Balin H, Glasser S, eds. Re- productive biology. Amsterdam: Excerpta Medica, 1972:23 4. Hayles AB, Cloutire MD. Clinical hypothyroidism in the young— a second look. Symp Endocr Disorders 1972:56:871 5. Scow RO, Simpson ME. Thyroidectomy in the newborn rat. Anat Rec 1945;91:209 6. Ortega E, E, Ruiz E. Activity of the hypothalamo- pituitary ovarian axis in hypothyroid rats with or without tri- iodothyronine replacement. Life Sci 1990;46:391 7. Takacs-Jarrett M, Broot BC. Steroid secretion by follicles and cysts from the hypothyroid, hCG-treated rat. Sac Experimental BioI Med 1994;207:62 8. Vriend J, Bertalanffy FD, Ralcewicz TA. The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in fe- male Syrian hamsters. Bioi Reprod 1987;36:719 9. Maqsood M. Thyroid functions in relation to reproduction of mammals and birds. Bioi Rev 1952;27:281 10. Bonet B, Herrera E. Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat. Endocrinology 1991;129:210 11. Rao PM, PandaJN. Uterine enzyme changes in thyroidectomized rats at parturition. J Reprod FertiI1981;61:109 12. Nesbitt REL, Abdul-Karim RW, Prior JT, TF, Rourke JE. Study of the effect of experimentally induced endocrine insults upon pregnant and nonpregnant ewes. m. ACfH and propyl- thiouracil administration and the production of polycystic ovaries. Fertil Steril1967;18:739 13. Ruh MF, Ruh TS, Klitgaard HM. Uptake and retention of estro- gens by uteri from rats in various thyroid states. Proc Soc Bioi Med 1970;134:558 14. Kirkland JL, Gardner RM, Mukku VR, Akhtar M, Stancel GM. Hormonal control of uterine growth: The effect of hypothy- roidism on estrogen-stimulated cell division. Endocrinology 1981;108:2346 15. Moenter SM, Woodfill CJI, Karsch FJ. Role of the thyroid gland in seasonal reproduction: Thyroidectomy blocks seasonal suppres- sion of reproductive neuroendocrine activity in ewes. En- docrinology 1991;128:1337 16. Dawson A. Thyroidectomy progressively renders the reproduc- tive system of starlings (Sturnus vulgaris) unresponsive to changes in daylengtll. J EndocrinoI1993;139:51 17. Kendle F. Case of precocious puberty in a female cretin. Br Med J 1905;1:246 18. Van Wyk J, Grumbach MM. Syndrome of precocious menstrua- tion and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap pituitary feedback. J Pediatr 1960;57:416 19. R, Reid RL. Thyroid disease and reproductive dysfunc- tion: a review. Obstet GynecoI1987;70:789 20. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. AmJ Obstet GynecoI1989;160:673 21. Higham]M, Shaw RW. TIle effect of thyroxine replacement on menstrual blood loss in a hypothyroid patient. Br J Obstet Gy- naecol 1992;99:695 22. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimu- lation syndrome associated with hypothyroidism. Am J Obstet GynecoI1989;160:1220 23. Goldsmith RE, Sturgis SH, Lerman J,. Stanbury JB. The menstrual pattern in thyroid disease. J Clin Endocrinol Metab 1952;12:846 24. Wakim AN, Polizotto SL, Buffo ML, Marrert;> MA, Burholt DR. Thyroid hormones in human follicular fluid and thyroid hor- mone receptors in human granulosa cells. Fertil Steril 1993;59:1187 25. Channing CP, Tsai V, Sachs D. Role of insulin, thyroxine and cor- tisol in luteinization of porcine granulosa cells grown in chemi- cally defined media. Bioi Reprod 1976;15:235 26. Gerhard I, Becker T, Eggert-Kruse W, Klinga K, Runnebaum B. Thyroid and ovarian function in infertile women. Hum Reprod 1991;6:338 27. LE, Leveno KJ, Cunningham FG. Hypothyroidism compli- cating pregnancy. Obstet Gynecol1988;72:108 28. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JR. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993;81:349 29. Nikolaj TF, Mulligan GM, Gribble RK, Harkins PG, Meier PR, RC. Thyroid function and treatment in premenstrual syn- drome.J Clin Endocrinol Metab 1990;70:1108 30. Roti E, Minelli R, Gardini E, Braverman LE. The use and misuse of thyroid hormone. Endocr Rev 1993;14:401 852 31. Burrow GN, Fisher DA, Larsen PRo Maternal and fetal thyroid function. N EnglJ Med 1994;331:1072 32. CRW, Forsyth lA, Besser GM. Amenorrhea, galactorrhea and primary hypothyroidism with high circulating levels of pro- lactin. Br MedJ 1971;3:462 33. Van Campenhout J, Van J, Antaki A, Rasio E. Diabetes mellitus and thyroid autoimmunity in gonadal dysgenesis. Fertil Steril 1973;24:1 34. Vallotton ME, Foibes AP. Autoimmunity in gonadal dysgenesis and Klinefelter's syndrome. Lancet 1967;1:648 35. Refetoff S, Selenkow HA. Familial thyroxine-binding globulin deficiency in a patient with 's syndrome (XO). N Engl J Med 1968;278:1081 36. Longcope C, Abend S, Braverman LE, Emerson CR. Androstene- dione and estrone dynamics in hypothyroid women. J Clin En- docrinol Metab 1990;70:903 37. Gallagher TF, Fukushima DK, Noguchi S, et al. Recent studies in steroid hormone metabolism in man. Recent prog Horm Res 1966;22:283 38. Saenger P. Abnormal sex differentiation. J Pediatr 1984;104:1 39. Lynn WG. The thyroid gland and reproduction in cold blooded vertebrates. Proceedings of the Fifth Mid-West Conference Thy- roid 1969;17 40. Palmero S, de Marchis M, Gallo G, Fugassa E. Thyroid hormone affects the development of Sertoli cell function in the rat. J En- docrinoI1989;123:105 41. Kirby JD, Jetton AE, Cooke PS, et al. Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced in- crease in adult testicular size and sperm production in the rat. Endocrinology 1992;131:559 42. Van Haaster LH, de Jong PH, Docter R, De Rooij DG. The effect of hypothyroidism on Sertoli cell proliferation and differentia- tion and hormone levels during testicular development in the rat. Endocrinology 1992;131:1574 43. Hardy MP, Kirby]D, Hess RA, Cooke PS. Leydig cells mcrease their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 1993;132:2417 44. Gomes WR. Metabolic and regulatory hormones influencing testis function. In: AD, Gomes WR, Vandemark NL, eds. The testis. Vol III. Influencing factors. New York: Academic Press, 1970:67 45. Chubb C, Henry L. The fertility of hypothyroid male mice. J Re- prod Fertil1988;83:819 46. dIandrasekhar Y, Holland MK, D'Occhio Mj, Setchell BP. Sper- matogenesis, seminal characteristics and reproductive homlone levels in mature rams with induced hYPQthyroidism and hyper- thyroidism. J EndocrinoI1985;105:39 47. Weiss SR, Burns JM. The effect of acute treatment with two goitrogens on plasma thyroid hormones, testosterone and testic- ular morphology in adult male rats. Comp Biochem Physiol (A) 1988;90A:449 48. Castro-Magana M, Angulo M, Canas A, Sharp A, Fuentes B. Hy- pothalamic-pituitary gonadal axis in boys with primary hypothy- roidism and macroorchidism. J Pediatr 1988;112:397 49. Wortsman J, Rosner W, Dufau ML. Abnormal testicular func- tion in men with primary hypothyroidism. Am J Med 1987; 82:207 50. Steinberger E. The thyroid gland in male infertility. In: C-R, Mastroianni LJr, Amelar R, Dubin 1, eds. Current therapy of infertility 1982-1983. St Louis: CV Mosby, 1982:15 51. De La BaIze FA, Arrilloga F, Mancini RE. Male hypogonadism in hypothyroidism: a study of six cases. J Clin Endocrinol Metab 1962;22:212 52. Griboff S. Semen analysis in myxedema. Fertil Sterill962;13:436 53. Cavaliere H, Abelin N, Medeiros-Neto G. Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. J AndroI1988;9:215 54. De Nayer P, Lambot MP, Desmons MC, Rennotte B, Malvaux P, Beckers C. Sex homlone-binding protein in hyperthyroxinemic patients. A discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab 1986;62:1309 55. s RC, son SD. Pathologic changes in adult myxedema: survey of 10 necropsies. j Clin Endocrinol Metab 1957;17:1354 56. Marine D. Changes in the interstitial cells of the testis in Gull's disease. Arch PathoI1939;28:65 ____________________________ Author: Sheldon S. StofIer. MD Date Published: 01-Jan-1982 Publication: POSTGRADUATE MEDICINE. VOL 72/NO 2/AUGUST 1982 Title: Menstrual disorders and mild thyroid insufficiency Intriguing cases suggesting an association Category: reproductive Keywords: reproductive, problem, StofIer, Menstrual, disorder, mild, thyroid, insufficiency, case, suggest, association, pathology, patient, treat, levothyroxine, hypo, hyper, TSH, TRH Text: Should patients with menstrual dysfunction but without obvious uterine pathology be considered for thyrotoxin-releasing hormone (TRH) testing? In several cases described here. an apparent relationship between menstrual disturbance and minimal thyroid insufficiency was documented by the patients' dramatic response to treatment with levothyroxine. The association of overt hypothyroidism or hyperthyroidism with menstrual disturbance and infertility is well known.15 However, menstrual disturbance may also be related to minimal thyroid insufficiency, as the following cases suggest. The past ten years have brought enonnous advances in the ability to diagnose mild thyroid dysfunction. The introduction of serum thyroxine and serum thyroid -stimulating hormone (TSH) radioimmunoassays has increased the sensitivity and specificity of thyroid function testing. The serum TSH assay has been shown to be a sensitive indicator of diminished thyroid functional reserve. since TSH levels become elevated before circulating serum thyroxine levels fall below the normal range 6, Thyrotropin-releasing hormone (TRH) is a simple tripeptide nonnally found in the hypothalamus. Its availability in synthetic fonn, protirelin (Thypinone, Relefact TRH), has provided a convenient provocative test of pituitary TSH reserve and has further extended the sensitivity of thyroid testing. In fact, this TRH test is so sensitive that results may be markedly abnormal in patients with no signs or symptoms of thyroid disease.6 Patients with minimal impairment of thyroid functional reserve who have normal serum thyroxine and normal baseline serum TSH levels may have an augmented TSH response to TRH administration.6 76 76 Table 1. Results of thyroid function studies in four patients with menstrual disturbance treated by levothyroxine therapy Case Time of testing Thyroid function study FTI* Baseline TRH:+ TSHt 1 Initial study 2.2 6.0 58.0 After26mo of treatment 2.9 3.0 11.7 2 Initial study 1.9 7.1 57.3 After 6 mo of treatment 3.5 1.6 1.8 3 Initial study 1.7 Two years later 2.1 7.2 52.9 After 3 mo of treatment 2.0 1.2 After 21 mo of treatment 2.6 2.8 14.3 4 Initial study 1.8 9.3 >80 After2 mo of treatment 3.8 3.0 6.1 After 14 mo of treatment 1.7 16.4 >80 After 2 mo of increased 3.6 2.5 2.5 dosage * Free thyroxine index (total T4 x T3 resin uptake). normal range 1.4-4.0 +Thyroid-stimulating hormone by radioimmunoassay, normal <8.0 uU/mc tThyrotropin-releasing hormone test (serum TSH rise 20 min after administration of 100 ug TRH), normal range 2-20 uUI ml 80 ...... Discussion In the past, when thyroid test-ng was nonspecific, inaccurate, and insensitive, desiccated thyroid tablets were often given empirically to women with menstrual dysfunction and/ or infertility. Some of these patients may have improved, reinforcing this unscientific and currently unjustifiable approach. At least a portion of these women may have actually had subclinical, and at that time undetectable, thyroid insufficiency. ...... Recently, I encountered a 32 year-old patient with evidence of very mild thyroid insufficiency who had undergone hysterectomy four years before because of troublesome hypermenonorrhea The patient had a diffuse goiter 11/2 times normal size, and antimicrbsomal antibodies were positive at 1:6,400 dilution. Serum FTI was 1.5, baseline serum TSH was 6.3 µU/m1, and serum TSH 20 minutes after TRH administration was 60.7 µU/m1. The pathology report revealed a normal-sized uterus With a predominantly proliferative endometrium and a normal myometrium. Although mild thyroid dysfunction cannot be proven responsible for this patient's abnormal menstrual bleeding, one wonders if TRH testing could have avoided the need for hysterectomy in this case and perhaps in similar cases. ...... 82 ...... Recommendations Based on my experience, I would recommend that patients \vith long- standing menstrual dysfunction without obvious uterine pathology be considered for TRH testing. Such testing would be especially fruitful in patients with goiter, high-nrmal baseline serum TSH value, or family history of thyroid disease. I would certainly not encourage empirical use of thyroid hormone in such a patient population without appropriate testing. Because mild thyroid insufficiency is so easily treated, TRH testing and atrial of thyroid hormone therapy, if .indicated, should be considered in difficult cases of menstrual dysfunction prior to hysterectomy. Summary Three cases of menstrual disturbance possibly related to minimal thyroid insufficiency are reported. In all cases, tltyrotropin- releasing hormone testing was sensitive enough to detect evidence of tltyroid abnormality .Without exception, treatment with levothyroxine caused a dramatic end to menstrual difficulty. In two of these cases, levotltyroxine tlterapy was discontinued and the menstrual abnormality returned. Resumption of levotltyroxine treatment led to prompt retum of normal menstruation. A fourth case is presented which suggests tltat placebo effect alone is probably not responsible for the observed menstrual improvement. It is possible that minimal thyroid insufficiency can lead to marked menstrual disturbance. References I. Goldsmith RE. Sturgis SH. Lennan J. et a!. The menstrual pattern in thyroid disease J Clin Endocrinol Metab 1952 12: 846-55 2. Distiller LA. Sage1 J. Morley JE. et a!. Assess ment of pituitary gonadotropin reserve using luteinizing hormone releasing hormone (LRH) in states of altered thyroid function J Clin Endocrinol Metab 1975:40, 512-15 3. Keye WR. Yuen BH. KnopfRF. et a!. Amenorrhea yperprolactinemia, and pituitary enlargement secondary to primary hypothyroidism Obstet Gyneco 1976:48,697-702 4. Van Wyk JJ. Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism an example of hormonal overlap in pituitary feedback J Pediatr 1960:57,416-35 5. Tolis G. Hoyte K. McKenzie JM. et al. Clinical.biochemical and rndlologic reversibility of hyperprolactinemic galactorrhea.amenorrhea and abnorma sella by thyroxine in a patient with primary hypothyraidisrn Am J Obstet Gynecol 1978:131, 850-2 6. Ingbar SH. Woeber KA. The thyroid gland In: Willams R. ed, Textbook of endocrinology 6th ed Philadelphia WB Saunders, 1981: 117- 247 7. Buchanan GC. Tredway DR. Pittard JC. et a!.Gonadotropin secretion and hypothyroidism Obstet Gynecol 1977: 50,392-6 S. CoUu R. Abnormal pi tui tary hormone response to thyrotropin- reieasing hormone an index. of central nerve system dysfunctlon In Tolis G, Labrle, F JB, et al. eds Cllnical neuroendocrinology a pathophysiological approach New York Raven Press 1979: 129-37 9. Snyder PJ. s LS. Utige RD et al. Thyroid hormone inhibitlon of the prolactin response to thyrotropin-releasing hormone J Clin Invest 1973: 52,2324-9 10. Tolls G. Prolactin physiology and pathology In: Krieger DT JC eds Neuroendocrinology Sunderland. MA Sinauer Assoc, 1980: 34,322-8 11. Powers JM. Block MB. Primary hypothyroidlsm with reversible hypeprolactinemia and pituitary enlargement Ariz Med 1989:37, 256-8 12. Stoffer SS. McKee1 DW Jr. Randall RV, et a!. Pituilary prolactin cell hypetplasia with autonomous prolactin secretlon and primary hypothytoidism Fertil Steril 1981: 36,682-5 __________________ Author: Luoto R Date Published: 27-Jun-1997 Publication: Int J Epidemiol 1997 Jun;26(3):476-83 Title: Hysterectomy and subsequent risk of cancer. Category: reproductive Keywords: Luoto, Hysterectomy, subsequent, risk, cancer, Elevate, papillary, thyroid, follow, reproductive, endocrinological, cause, high, breast, peri, retrospective, study, menopause, total, pre Text: BACKGROUND: The objective of this retrospective cohort study was to assess the effect of hysterectomy on subsequent risk of cancer among 25,382 hysterectomized and a similar number of non- hysterectomized control women, registered in 1963-1976 in the Mass Screening Registry (MSR). METHODS: Cancer cases were obtained from the Finnish Cancer Registry (FCR) and standardized incidence ratio (SIR); the expected number of cases based on cancer incidence rates of the Finnish female population in 1967-1993, was used. Relative risk (RR) was calculated as SIR among the hysterectomized relative to non-hysterectomized women, adjusted for follow-up, education and parity. RESULTS: The RR estimates of non-genital cancers among women with any hysterectomy were approximately 5% higher than in the non- hysterectomized cohort. Relative risks of rectal cancer (RR = 1.4, 95% confidence interval [CI]: 1.0-1.8) and thyroid cancer (RR = 2.1, 95% CI; 1.5-3.1) were significant and largest among women who had undergone total hysterectomy pre- or perimenopausally. Relative risk estimates of breast cancer were close to unity. CONCLUSIONS: Hysterectomy is not associated with any substantial protective or promoting effect on cancers in general. Elevated risk of papillary thyroid cancer following hysterectomy is biologically plausible, as there are reproductive and endocrinological causes of thyroid cancer. National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland. PMID: 9222770 [PubMed - indexed for MEDLINE] _____________________ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 19, 2005 Report Share Posted March 19, 2005 I don't believe coffee is a problem. Have you ever noticed that people are willing to give up coffee for their fibroids, but won't give up chocolate even though it has some bad things in it that are just as bad as coffee? I started to think, after being on fibroid newsgroups for three years, that people think that if it's good and give pleasure, then somehow it's bad for fibroids. Sort of like fibroids are caused by sin and if we sacrifice those things we love to be healed. The other notion people seemed to have a lot is that fibroids are the cause stuck energy and emotional issues that are not worked out. This one is one of those classic " blame the victim " notions. You are the cause of your own illness and if you can somehow fix your sick mind or maybe " find God " or do some peace work, you will be cured and your punishment removed. I suppose coffee does increase adrenal output and this might raise cortisol and high cortisol tends to increase estrogen. But, I don't know how you could say coffee is any worse than a serving of beans or nuts or drinking out of plastic or spraying weeds in your yard with pesticides or eating meat of animals given growth hormone and on and on. Where do you draw the line? The biggest cause of fibroids in my book is low thyroid, combined with genetics, and stress, which plays into the thyroid problems. A big study was done in Italy on eating habits and fibroids. The only thing they could find that correlated was the amount of red meat eaten. The correlation was very weak at best and did not really prove it unequivically. Tish ______________________ Here are some things I have collected on this topic. ______________________ But menstrual irregulaities are not the only hrmful affect low thryoid has on the uterus. A lack of thyroid greatly enhances the growth of uterine fibroids as well. If a woman is on sufficient amounts of thyroid the further growth of uterine fibroids usually will be blocked and frequently they will start shrinking. Besides uncontrolled bleeding, the major reason that women have hysterectomies is symptomatic uterine fibroids which can cause discomfort and contribute to excessive bleeding. Hypothyroidism also increases the incidence of uterine cancer which is the reason behind most the remaining hysterectomies. So thyroid has an almost magical impact on many of the woes associated with womanhood; it takes them away. (Page 117) And as mentioned elsewhere, there is a close relationship between the binding sites of thyroid and the binding sites of estrogen, so the function of thyroid and estrogen are intertwined in subtle ways. (Page 116) " Thyroid, Guardian of Health " by Philip G. Young, MD, Trafford Publishing, , BC., Canada, 2002 __________________________ Fibroid tumors have been rare in hypothyroid women who have been maintained on adequate thyroid therapy. It is possible to produce fibroids in experimental animals by injection of estrogens, and there is evidence of excess of estrogens in hypothyroid women. In hypothyroidism, there is increased activity of the pituitary gland aimed at trying to stimulate the thyroid to produce more hormone secretions, and the increased pituitary activity may spill over to affect ovaries and increase their estrogen output. (Page 133) " Hypothyroidism: The Unsuspected Illness " by Broda O. , M.D. and Lawrence Galton, Harper & Row, Publishers, New York, 1976 ________________ [Diagnosis of thyroid function in uterine myomatosis] [schilddrusenfunktionsdiagnostik bei Myomatosis uteri.] Zentralbl Gynakol 1989;111(1):47-52 (ISSN: 0044-4197) Lange R; Meinen K Gynakologisch-Geburtshilflichen Abteilung, St. Lukas Klinik Solingen. A correlation between thyroid disease and uterine myoma has been discussed till the fourth decade of this century. Since then, this possible connection was given no further notice. We examined 79 women needing a hysterectomy for various reasons regarding myometrial histology, thyroid function and thyroid antibodies. The patient group bearing myomas showed significantly more frequent (23%) pathological TRH/TSH stimulation tests results than the control group (3.7%, p = 0.0543). 10 of 22 patients with myomas had microsomal and/or thyroglobin antibodies, compared with none in the control group (n = 17, p = 0.0019). Therefore regarding these results a connection between thyroid disease and uterine myoma should undergo a more detailed examination. ______________________________ Part B - Oestrogen, Progesterone & Testosterone The hormones that keep us male and female are crucially affected by thyroid and adrenal function; and in turn can effect the proper functioning of the thyroid itself. So let us see where they fit in. Since my approach to metabolic problems is holistic, we have to ask if thyroid and adrenal insufficiency may be altered or worsened by deficiencies elsewhere. The answer is of course, yes. Since a state of lowered metabolism means that nothing really works as it was designed to, it follows that other hormone producing glands may not do their job properly either. It is a bit like an extraordinarily complex piece of electrical machinery, designed for 240 volts, running on 210 volts. It runs, but the lights look a bit dim and flicker a bit. Bringing up the voltage - gently - will get everything working again. So far as other components of the endocrine system go, we must be prepared for partial recovery only, and supplementation may well be indicated elsewhere as well. We are talking mostly about sex hormones here, and the effects of the menopause on both sexes. We have learnt already how important the adrenal corticosteroids are in the maintenance of the body's normal health; the male and female sex hormones, which are of course also steroids, are just as extraordinarily important in their own right. (It may have perhaps surprised you to realize that the whole body, most especially many of its hormones, is based on the steroid molecule. The use of the word " steroid " has been denigrated in the popular mind as being potentially, if not actually, dangerous, and this is a complete distortion. The contraceptive pill, for which millions of prescriptions are written weekly, is based on two steroids and few doctors and few patients are especially concerned that they do in fact belong to the great family of steroids). We will start with the female menopause, which will be hastened or worsened by a low thyroid/adrenal state. Literally, the menopause means " the last period " . For some women this is an abrupt thing, there one month and gone the next. Very often the process is rather more protracted than this; the periods start lengthening and sputter about; they may become heavy with pain and floods, or become very light and irregular. And menstrual problems, with heavy irregular periods, are certainly associated with low thyroid. So we need to have a look at the whole business, so that we can decide to intervene if necessary while treating the metabolic problems. Women actually produce three different sex hormones, oestrogen (which has three different forms: oestradiol, oestrone and oestriol), progesterone and testosterone. You thought testosterone was a male hormone, didn't you. Well, it is; but women produce it too - though less than men of course. (The reverse is also the case.) In general oestradiol, the main oestrogen, comes from the ovaries, the other two from the adrenals, directly or indirectly, and more after the menopause. The way it all works is this. As the menarche (the start of periods) approaches, the ovaries start to produce oestrogen and under the influence of a pituitary hormone, the Follicle Stimulating Hormone (FSH), an ovarian follicle (of which there are many hundreds containing egg cells waiting their time) matures an ovum which surfaces about mid cycle and is released. It finds its way into one of the fallopian tubes (right or left, depending on which ovary produced the ovum) where it may or may not be fertilized. The place from where it was released on the ovary undergoes a change to produce the Corpus Luteum or " Yellow Body " . This structure begins to produce under the influence of Luteinizing Hormone (LH) from the pituitary, another hormone, progesterone. This prepares the lining of the womb for implantation if the ovum is fertilized. Oestrogen and progesterone are produced together for the second half of the cycle; and then the supply is cut off abruptly which starts off the menstrual period. Hypothyroidism can affect this process in several ways. To start with, a low thyroid state affects the onset of the first period, oddly enough in two opposing ways. The first period may come unusually early at 8, 9 or 10 years old; or, it may come unusually late, 15, 16 or 17 years old. Periods starting abnormally like this should raise a suspicion about the thyroid at once. The periods may be abnormal in other ways. They may be exceedingly painful with collapse and prostration of the unfortunate girl; they may be very heavy or very light or come at irregular times. There may be premenstrual tension to make life miserable. These problems may occur at any time of life, but may sort themselves out a bit after having children. Then in the later thirties and early forties it all goes wrong and flooding and terrible PMT may ruin things so badly that relationships suffer. The gynecologist may not think of thyroid dysfunction as a cause and the ladies then become the target of various synthetic hormone combinations, which may or may not bring relief. It is at this point, of course, that hysterectomy becomes the treatment choice, and worn out with it all, the unhappy sufferer consents to surgery. Relief from the terrible periods may well justify the hysterectomy for the patient; but it may have missed the point altogether. As I said earlier, hysterectomy is very likely to affect thyroid activity. There seems to be a chemical dialogue between the womb and the thyroid; and interference - including sterilization, termination, or even a D&C, seems to damage thyroid function for many. The weight gain, which nearly always occurs, is not due to comfort eating while grieving for one's lost fertility, but because thyroid activity may be further damaged. This, and the other symptoms of a running down of thyroid activity, is a heavy price to pay for an operation for which one out of every three, at least, wasn't necessary and could have been avoided if thyroid status had been properly assessed and treated. The other worry which besets women at this time of their lives is premenstrual tension (PMT) or as the Americans call it (PMS) premenstrual syndrome. Some doctors won't have that this occurs at all. I remember reading an authoritative article by a lady doctor who discounted it completely; one just wonders what planet she came from. Not only is it a very real problem; if anything it is getting worse. Although a number of causes have been cited, it seems clear that it is associated with an imbalance between the oestrogen and progesterone production. This last, may drop anyway with the general loss of viability of the ovum and the corpus luteum; but it is much worse with deficient thyroid hormone. Throughout my experience with low thyroid, I have been staggered to find that some women lose their PMT within a month or so of starting their thyroid supplementation - simply the result of improved progesterone production. Where progesterone production in the mid thirties and forties has not been improved by thyroid supplementation, very thoughtful consideration must be given to the provision of progesterone supplementation. The standard way of doing this is by the use of a group of artificial progesterones, which are called progestogens and the synthetic hormone Norithesterone is an example. While these may well be helpful for some women, they have a number of side effects which have made them less and less popular; nevertheless, an alternative must be sought. As oestrogen dominance brings with it its own problems of bloating, weight gain and increased risk of cancer, a progesterone supplementation is essential. Of increasing popularity nowadays is the use of natural progesterone, which is actually extracted from plants and is incorporated in creams which may be simply rubbed into the skin daily. Although establishment thinking is, as might be expected, somewhat suspicious of the natural product, favoring the artificial, very many thousands of women are greatly benefiting from transdermal progesterone (see Appendix D). Another worrying result of a reduction in thyroid function is a reduction of red blood cell production; many people are troubled by a refractory anaemia (when it is unresponsive to treatment), which adds to their general lack of well-being and exhaustion. How much worse is it then, when heavy prolonged periods are added to the problem.. . Iron, folic acid and vitamin C would seem to be essential, especially in the early phases of treatment. A most alarming gap in the management of infertility, is the failure to realize that a prime and a gravely neglected cause is hypothyroidism. It is obvious that there are several ways the healthy ovum can be affected: its production, its maturation, proper fertilization and implantation....... (Pages 135 - 139) " The Great Thyroid Scandal and How to Survive It " by Dr. Barry Durrant-Peatfield MB BS LRCP MRCS, Barons Down Publishing, London, 2002, ___________________________ Ginecol Obstet Mex. 1969 Dec;26(158):777-85. [Report on the relation between limited hypothyroidism and uterine fibromyomatosis] [Article in Spanish] Gutierrez JT. PMID: 5408031 [PubMed - indexed for MEDLINE (Paper can be purchased from PubMed) _____________________ Akush Ginekol (Mosk). 1988 May;(5):46-50. [The reproductive system of patients with disordered thyroid function] [Article in Russian] Sosnova EA. PMID: 3177773 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ___________________________ J Assoc Physicians India. 1993 Feb;41(2):88-90. Comment in: J Assoc Physicians India. 1993 Nov;41(11):761-2. Hypothyroidism presenting with polycystic ovary syndrome. Sridhar GR, Nagamani G. Endocrine & Diabetes Centre, Visakhapatnam. During a 30 months period, two women of primary hypothyroidism (2/13; 1.04%) presented with features of polycystic ovary syndrome (PCOS). In hypothyroidism, sex hormone binding globulin levels are decreased; increased conversion of androstenedione to testosterone, and aromatization to estradiol are present, all these being an exaggeration of biochemical changes characteristic of PCOS. Besides, metabolic clearance rates of androstenedione and estrone, the putative mediators of PCOS, are reduced. Hypothyroidism can either initiate, maintain or worsen the syndrome. Correction of hypothyroidism when present, would therefore form an important aspect in the management of infertility associated with PCOS. Publication Types: Case Reports PMID: 8053991 [PubMed - indexed for MEDLINE] __________________ Pediatr Akus Ginekol. 1968 Sep-Oct;5:55-8. [Function of thyroid gland in uterine fibromyoma] [Article in Ukrainian] Sol's'kii IaP, Chizhova PS, Ivaniuta PI. PMID: 5743398 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _______________________ Akush Ginekol (Mosk). 1970 Oct;46(10):24-7. [Functional status of the thyroid gland in patients with uterine myoma] [Article in Russian] Vasilevskaia LN, Kotliarov EV. PMID: 5519731 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _________________ Ginecol Obstet Mex. 1974 Jun;35(212):657-80. [Edocrinal study of uterine fibromyoma] [Article in Spanish] Nava y R. PMID: 4138171 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ____________________ Akush Ginekol (Mosk). 1967 Oct;43(9):17-21. [Adrenal cortex and thyroid gland function in patients with myoma of uterus] [Article in Russian] Slepov MI, Novouspenskaia IE. PMID: 5607969 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ________________ Author: GRIFF T. ROSS, M.D., Date Published: 01-Jan-1958 Publication: Journal of Clinical Endocrinology and Metabolism 18: 492-500, 1958 Title: SEVERE UTERINE BLEEDING AND DEGENERATIVE SKELETAL-MUSCLE CHANGES IN UNRECOGNIZED MYXEDEMA Category: reproductive Keywords: reproductive, problem, ROSS, SEVERE, UTERINE, BLEED, DEGENERATIVE, SKELETAL, MUSCLE, CHANGE, UNRECOGNIZED, MYXEDEMA, treat, women, menstruation, severe, anemia, normal, desiccated, thyroid Text: p 492 ABSTRACT Two cases of severe uterine bleedng associated with unrecognized myxedema (hypothyroidism) are reported. Degenerative changes in skeletal muscles were suggested by the results of electromyographic studies and demonstrated by biopsy of a muscle prior to treatment in one patient. The uterine bleeding stopped promptly and a normal menstrual cycle was re-established in both patients after treatment with desiccated thyroid. DISTURBANCES in thyroidal function in premenopausal women are often associated with abnormalities of menstruation. Either menorrhagia or amenorrhea may develop in patients with spontaneous or postoperative myxedema. However, when amenorrhea occurs in a premenopausal women with the secondary hypothyroidism the diagnosis of hypopituitarism should be considered and excluded. In his book, Means stated: " Menorrhagia may be sufficiently impressive in ordinary myxedema so that in several cases that have come to our attention patients have actually had a dilation and curettage for it when all they needed was desiccated thyroid for treatment. " We are reporting 2 cases of profuse uterine bleeding with severe anemia secondary to unrecognised primary myxedema, in which prompt cessation of uterine bleeding and restoration of normal menstrual cycles followed the oral administration of desiccated thyroid. Significant degenerative changes in the skeletal muscles were suggested by the results of electromyography and were demonstrated by muscle biopsy prior to treatment in one of these patients. p 494 .. ....COMMENT Both these patients were referred for consideration of surgical treatment for intractable profuse uterine bleeding. Severe menorrhagia lasting from p495 six to ten days had been present during the six months preceding the admission of the first patient to the hospital. After the clinical recognition of myxedema, it was realized that the bleeding might be due to the hypothyroidism. For this reason, operation was deferred until the patient could be restored to euthyroid state. After five days of oral treatment with desiccated thyroid, the uterine bleeding ceased. The menstrual pattern subsequently returned to normal with regard to periodicity and flow. Despite the fact that the second patient had noted intermenstrual spotting for many years, the myxedema in all probability began after her last pregnancy in 1950. There was nothing to suggest anterior- pituitary insufficiency, since the patient lactated and cyclic menstrual periods were re-established following parturition. She was extremely exsanguinated on admission, as shown by the clinical picture of mild shock and severe anemia. Her response toe desiccated thyroid was most gratifying, since the uterine bleeding stopped after seven days of therapy. A checkup after three months off treatment revealed that she was clinically euthyroid. A remarkable change had taken place in the facies (Fig. 1). normal menses had returned. __________________ Author: JENNINGS C. LITZENBERG, M.D. Date Published: 01-Jan-1937 Publication: JAMA, 109:1871-1873, 1937 Title: THE ENDOCRINES IN RELATION TO STERILITY AND ABORTION Category: reproductive Keywords: reproductive, problem, LITZENBERG, ENDOCRINE, RELATION, STERILITY, ABORTION, fertile, pregnancy, develop, hormone, fetus, basal, metabolic, rate, menstrual, thyroid, women, normal Text: p1871 The endocrines govern the physiology of reproduction from beginning to end; spermatogenesis, ovogenesis, maturation of the ovum, ovulation, fertilization, preparation of the endometrium for nidation, implantation of the fertilized ovum, placentation, maintenance of pregnancy, development of the fetus, birth and lactation - all are dependent on hormones initiated and controlled by the anterior hypophysis. p1872 .....THE THYROID AND STERILITY Since 1922 I have studied the relation of the basal metabolic rate to sterility, abortions, and menstrual disturbances. In our first small series of sixty-nine consecutive sterile women, in whom no other evidence of myxedema was present, 50 per cent had a low basal rate; adding those who had conceived but aborted the figure was 56 per cent. Carefully supervised thyroid medication resulted in 33.3 per cent conception, 14 per cent of whom aborted. One woman conceived three times under thyroid medication, bringing the percentage of conceptions to 40. In another group of 114 women, 45 per cent of the married women were sterile and 40 per cent of the entire group had functional disturbances of menstruation. In a second series of 137 women, approximately the same figures were obtained, but in addition we found that 63 per cent had abnormal menses (our patients all came from a goiter area). Our third series (including the pervious reports) consists of 255 married women, 49.7 per cent of whom were sterile. Of 332 women, married and unmarried, 33.5 per cent had functional disturbances of menstruation. During the fifteen years of our experience to date (including cases not previously reported) there was a consistent rate of conceptions of 30 per cent in women with low basal rates. Haines and Mussey of the Mayo Clinic confirmed our thyroid treatment of functional menstrual disturbances, saying: " Because of a desire to determine the effectiveness of thyroid medication alone, in the treatment of certain menstrual disturbances, no patient received any other treatment. All were definitely improved; amenorrhea, 72 per cent; oligomenorrhea, 55 per cent; menorrhagia, 73 per cent, and general health, 75 per cent. " Also in this connection Haskins says: " Most gynecologists agree that thus far, of all the gland products, thyroid has proved to be the most useful for a variety of endocrine disturbances, including amenorrhea, oligomenorrhea, menorrhagia, sterility and abortion. " Marine, long ago (1917) when there was scarcely any usable knowledge of the endocrines, declared: " The relation of the thyroid to the sex organs in the female is the most frequent and classical illustration of the interrelation of the function of glands with internal secretions. " adds testimony by saying " The sole endocrine preparation that has proved itself of real value has been thyroid extract, which is of use in patients with lowered basal metabolism. " Novak declared that thyroid medication in sterility and abortion are more often efficacious than any other form of organotherapy. Desiccated thyroid was the first, and is still one of the few successful, substitutional hormone preparations. Perhaps when one gives desiccated thyroid one is doing to the ovaries what the pituitary has failed to do through stimulation of the thyroid gland by means of the thyrotropic hormone. I quote the concluding paragraph of an editorial in THE JOURNAL: These reflections [criticisms of the misuse of sex gland hormones] are not intended to inhibit chemical and biologic studies in accredited laboratories. Neither do they apply to the carefully controlled clinical application of accepted knowledge by competent observers; this is necessary. Rather are they intended (1) to emphasize that there is a great discrepancy between laboratory knowledge of the hormones and their clinical application, (2) to suggest that for the present only those clinicians with facilities for critical study be encouraged to administer the newer endocrine preparations to patients and that these clinicians be urged to publish their negative as well as their positive results, and (3) to suggest that a large group of physicians not represented in either of the groups mentioned cease their undiscriminating injection of unknown substances into unsuspecting patients. Physicians are perhaps cynical because of our limited knowledge of the endocrines and the complexity that faces it, but the tendency is to optimism when it contemplates the accomplishments of the recent past with their great promise for the future. _____________________ Author: RUTH C. FOSTER Date Published: 01-Jan-1939 Publication: ENDOCRINOLOGY 24:383,1939 Title: THYROID IN THE TREATMENT OF MENSTRUAL IRREGULARITIES Category: reproductive Keywords: reproductive, problem, FOSTER, THYROID, TREAT, MENSTRUAL, IRREGULAR, women, period, basal, metabolic, pelvis, metrorrhagia, amenorrhea, bleed, relief, continue, normal, desiccated Text: p383 DURING THE PAST few years we have been impressed by the efficacy of thyroid medication in the treatment of menstrual irregularities. Because our series of cases has shown results similar to those reported by clinicians working elsewhere, it has seemed worth while to summarize our data and present it in confirmation of material published previously. Fifty cases treated with thyroid have been observed for a period of from one to four years. These patients have been seen at least twice a month. Their ages have ranged from 16 to 34, although 41 of the series have been under 22 years of age. All have had complete physical examinations, pelvic studies, and repeated basal metabolic determinations. With a few exceptions, which will be discussed later, only those who showed no pathology in the pelvis have been treated with thyroid. .....Among this group of patients 25 complained of dysmenorrhea which was of sufficient severity to cause repeated absence from classes. Seventeen complained of scanty or delayed menstrual periods with intervals of as long as three months. Thirteen complained of too frequent periods or of inter-menstrual bleeding, while 7 had excessive flow together with the metrorrhagia. There were 5 cases of amenorrhea which was of 7 months to 4 years duration. Four of the patients had normal periods but there was a marked irritability with inability to concentrate for as long as a week prior to the period. p385 Of the 17 cases of oligomenorrhea, all reported definite relief as long as they continued taking thyroid. Several of this group tried going without therapy during the summer vacation but returned in the fall asking to resume treatment because their symptoms had recurred. All stated they felt much better when having their regular periods. .....The group of patients who complained of amenorrhea is small due to the fact that pathology was found to explain the cessation of periods in many of those who had this complaint. Those patients treated were given thyroid because their B.M.R. were low, and they or their parents wished them to receive a trial with thyroid before endometrial biopsies and further studies were made. p386 Those patients complaining of menorrhagia and metrorrhagia responded to thyroid therapy in a most satisfactory manner. The one failure was in a patient who had a large ovarian cyst removed because of prolonged menorrhagia. .....V.C., a university junior 18 years of age, consulted the Student Health Department because of a slight menstrual flow of six weeks duration, early fatigue, and a tendency towards a rapid gain in weight. She stated that her menstrual periods began when she was 13 and that they had always been irregular, occurring at intervals of three weeks to several months (9 months at one time). .....Treatment consisted of 1 to 2 gr. desiccated thyroid daily. The B.M.R. rose to -5, blood pressure to 108/78; the bleeding stopped and apparently normal periods occurred until the dose of thyroid was reduced, when there was a recurrence of the metrorrhagia. This patient has learned that she will have no symptoms I she takes thyroid in sufficient dosage to keep her B.M.R. -5 or above. This has been so consistent in her case that she can accurately predict her B.M.R. will be below these levels when the metrorrhagia recurs. p387 Four patients who complained of marked irritability prior to their periods are included in this series because their complaint was enough to interfere with their ordinary activities, and 3 did have relief with thyroid. Two noted partial relief, enough so that they did not want to stop thyroid medication. One had complete relief and one noted no difference. Thyroid was stopped several times but always with a recurrence of their symptoms. ..... DISCUSSION The explanation for the efficacy of thyroid medication in these cases can only be hypothesized. Experimental work in animals has shown that ablation of the thyroid is followed by an increase in size of the pituitary gland. Microscopic examination of these pituitaries shows hydropic degeneration, which explains the fact that after this procedure glands lose some of their potency. It may follow that in these patients there is an inadequate thyroid secretion resulting in a decrease in potency of the pituitary gland, which in turn causes inadequate gonad stimulation. One might go farther and state that the 4 patients who noted breast engorgement for the first time were having their first normal cycles with luteinization occurring. p388 Some of these problems may be solved by a study of endometrial biopsies before and after treatment. In a group of patients as young as these reported, most of whom are minors, it is difficult to obtain permission for biopsies from the parent, but as the public becomes educated to this procedure more parents should be willing to consent. It is our feeling that a B.M.R. should be obtained in all cases complaining of menstrual irregularities such as those reported above. Providing there is no pelvic pathology or physical condition to explain the symptoms, these patients should probably receive a trial with thyroid before further therapy is undertaken if their metabolic rates are below zero. It is understood that these patients will report periodically to their physicians and that the dose of thyroid will depend upon the individual response. In many cases there will be a complete relief of symptoms with small doses of thyroid although the metabolic rate has not reached what is considered the normal level. There is no way of predicting from the individual B.M.R. the degree of relief to be obtained. SUMMARY Fifty patients with ages ranging from 16 to 34 years were seen because of dysmenorrhea, oligomenorrhea, amenorrhea, metrorrhagia and menorrhagia. All were apparently healthy individuals with normal pelvic findings. These patients had B.M.R. ranging from -1 to -33 with an average of -15. All were treated with desiccated thyroid. Of 25 cases of dysmenorrhea 17 had complete relief, 5 partial, and 3 no relief. Of 4 patients with amenorrhea lasting from 8 months to 4 years only one had relief of her symptoms. Among 13 patients with metrorrhagia 12 had complete relief and of 7 with a menorrhagia 6 had complete relief. It is suggested that a B.M.R. should be determined in those individuals complaining of menstrual irregularities who have no demonstrable pathology to explain their symptoms. A therapeutic trial of thyroid is indicated if the B.M.R. is zero or below. ______________________ Author: BRODA O. BARNES M.D Date Published: 01-Jan-1949 Publication: MEDICINE January, 1949, Vol. 6, No. 1 pp. 33-34 Title: THE TREATMENT OF MENSTRUAL DISORDERS IN GENERAL PRACTISE Category: reproductive Keywords: reproductive, problem, BARNES, TREAT, MENSTRUAL, DISORDER, GENERAL, PRACTISE, thyroid, therapy, improve, patient, Basal, Temperature, relieve, bleed, women Text: The general practitioner can expect about 10 per cent of his patients to complain of menstrual difficulties. .....In 1939 and Thornton reported 50 cases of menstrual irregularities treated with thyroid therapy. Their results were far better than any published before or since. This present report of 143 cases is presented in confirmation of their work, and outlines an inexpensive plan of management which produces gratifying results. .....Control series for a group of cases of this kind are difficult. Each case serves as its own control for the period before therapy. Many of the patients relieved of their symptoms ceased medication and in a few months would have a return of their previous complaints. Thyroid therapy would again correct their menstrual difficulty. In view of the fact that the number of patients who were improved in the present series is almost identical, in proportion, with that of and Thornton in 1939, it seems reasonable to assume that the results are due to the treatment. SUMMARY One hundred forty-three cases of functional menstrual disorders have been studied. Dysmenorrhea, excessive bleeding and irregular menstrual cycles are included. The Basal Temperature usually is subnormal. Thyroid therapy relieves the symptoms in about 90 per cent of these cases. _______________________ Author: JOSEPH C. SCOTT, JR., M.D. Date Published: 01-Jan-1965 Publication: American Journal Obstetrics and Gynecology 90:161-165, 1965 Title: Menstrual patterns in myxedema Category: reproductive Keywords: reproductive, hypo, problem, pattern, myxedema, SCOTT, hypo, gland, menstruation, mild, test, menstrual, thyroid, hormone, menorrhagia, disease Text: 161 HYPOFUNCTION of the thyroid gland produces a broad spectrum of symptoms and signs, often including a change in the menstrual pattern. The various disorders of menstruation which may be associated with myxedema have been documented, but a difference exists in the reported frequency and types of abnormal menstrual pattern. Hypothyroidism has been implicated as the underlying cause of many irregularities of menstruation. .....Generally, it is believed that thyroid hormone is beneficial and its use is indicated only when there is evidence of thyroid hypofunction. A patient may be considered to be mildly hypothyroid by one clinician and euthyroid by another on the basis of only a single interview or test. No single test or procedure will define the status of the thyroid gland. Furthermore, any combination of methods may lead to erroneous interpretation or to inconsistent results. The clinician must have the faculty of correlating the clinical appearance of the patient with the laboratory findings. p 164 .....Comment Menorrhagia, that is, an increase in the amount and duration of menstrual flow, associated with myxedema may be mild, " occult, " or severe. Mild menorrhagia is a source of only minor concern and usually is corrected by better control of the myxedematous state. The term " occult menorrhagia " is warranted in cases in which there is excessive or prolonged menstruation which the patient considers to be normal. In these cases the onset of the menorrhagia has been so insidious that the patient is truly unaware of the change unless questioned closely (Case 2). Severe menorrhagia may require diagnostic curettage in addition to thyroid replacement therapy. Thyroid dysfunction should be considered in evaluation of each case of menstrual irregularity. Our studies reinforce the observations of other authors that menstrual disorders are not unusual in myxedema. A careful gynecologic examination should be performed for each patient suspected of having a thyroid disease. Any menstrual disorder should not be minimized and the possibility of genital malignant disease should be considered. Laboratory studies have greatly aided the clinicians in defining and evaluating thyroid disease states, but the " clinical appearance " of the patient should continue to be a prime factor in evaluation. Diagnostic measures, such as the quantitation of menstrual blood loss by tagging with radioactive chromium, are useful and informative in many patients, but not indispensable. Menorrhagia is the most frequent of the menstrual aberrations which are associated with myxedema. Hypomenorrhea and amenorrhea are much less common, and we have found oligomenorrhea to be rare. p 165 Summary The menstrual patterns of 50 premenopausal myxedematous women between 16 and 40 years of age were evaluated. Abnormal menstrual patterns occurred in 56 per cent of these patients. More than one form of menstrual irregularity was noted in two cases. Menorrhagia and metrorrhagia, alone or combined, constituted the abnormal patterns in 75 per cent of the patients. Amenorrhea occurs infrequently with myxedema. " Occult " menorrhagia should be considered in the evaluation of the patient with thyroid disease. _______________________ Author: Longcope Date Published: 30-Jun-1996 Publication: Werner and lngbar's The Thyroid, Seventh Edition, edited by E. Bravennan and D. Utiger. Lippincott-~ven Publishers, Philadelphia, @ 1996 Title: 71 The Male and Female Reproductive Systems in Hypothyroidism Category: reproductive Keywords: Longcope, reproduction, uterus, ovaries, hypo, thyroid, endometrial, muscle, animal, human, fertility, sexual, vagina, precocious, puberty, fetal, abort, testicular, sperm, libido Text: 849 HYPOTHYROIDISM IN THE FEMALE REPRODUCTIVE SYSTEM Hypothyroidism seems to affect the reproductive system in women more than in men. A review of the normal develop- ment and physiology of the female reproductive system has been given in chapter 47. Animal Studies In sheep, fetal hypothyroidism does not affect reproductive tract development but does result in prolonged gestation despite maternal euthyroidism.l However, in the rat, fetal hypothyroidism results in small ovaries deficient in lipid and cholesterol.2 Thyroidectomy of sexually immature rats results in delayed vaginal opening and sexual maturation; smaller ovaries and follicles than in controls3,4; and uteri and vaginas that are not well developed.5 When adult female rats are rendered hypothyroid their estrous cycles become irregular and their ovaries become atrophic.6 There is an enhanced response to HCG with the development of large cystic ovaries in hypothyroid rats.7 Hypothyroidism in hamsters and cows is associated with abnormal estrous cycles,s.9 and in hypothyroid hens there is a decrease in egg production.9 In the mature female rat, hypothyroidism apparently does not result in sterility but does interfere with gestation, especially in the fIrst half of pregnancy,lO with resorption of the embryo and subsequent reduction in litter size and an increase in stillbirths.ll In hypothyroid sheep, the uterus shows endometrial hyperplasia and smooth muscle hypertrophy, perhaps related to the prolonged estrous noted in hypothyroid ewes.12 Ruh and coworkers 13 reported increased estradiol binding in uteri of hypothyroid rats, but Kirkland and coworkers 14 found a decrease in the uterine response to estrogen in hypothyroid rats. Hypothyroidism inhibits the photoperiod responses and seasonal breeding patterns in sheep and birds.15,16 Human Studies and Clinical Aspects The reproductive tract appears to develop normally in cretins; thus, hypothyroidism during fetal life does not appear to affect the normal .development of the reproductive tract. Hypothyroidism in prepubertal years generally leads to short stature and may lead to a delay in sexual maturity.4 However, an interesting syndrome described by Kendlell and Van Wyk and Grumbach 18 occurs not infrequently: it is characterized by precocious menstruation, galactorrhea, and sella enlargement in girls with juvenile hypothyroidism. The cause is thought to be an overlap in the pituitary production of TSH and gonadotropins, with the latter causing early ovarian secretion of estrogens and subsequent endometrial stimulation with vaginal bleeding. Prolactin levels are elevated, leading to galactorrhea. However, there is no pubertal increase in the adrenal production of androgen precursors, so that axillary and pubic hair are usually not apparent.I8 Therapy with thyroxine in proper dosage results in prompt alleviation of the symptomatology. In adult women, hypothyroidism results in changes in cycle length and amount of bleeding I9-21 and has been reported 850 in association with the ovarian hyperstimulation syndrome.22 Menorrhagia is a frequent complaint and is probably due to estrogen breakthrough bleeding secondary to anovulation, which is frequent in severe hypothyroidism. 19 The anovulation is reflected in the frequent finding of a proliferative endometrium on endometrial biopsy.23 TRa-l and TRBB-1 receptors have been found in human granulosa cells and both triiodothyronine and thyroxine have been found in follicular fluid.24 Earlier work in- dicated that thyroxine enhanced the action of gonadotropins on luteinization and progestin secretion by cultured granulosa cells,25 and it has recently been noted that in a group of infertile women, those with elevated TSH levels had a higher incidence of out-of-phase biopsies than women with normal TSH.26 Ovulation and conception can occur in mild hypothyroidism, but in the past those pregnancies that did occur were often associated with abortions in the first trimester, stillbirths, or prematurity, 19,27 Recent studies indicate these events may be less common but that gestational hypertension occurs often in pregnant women with untreated hypothyroidism.28 Pregnancy occurring in women with myxedema has been reported to be uncommon,27 but this is somewhat hard to document and may be the result of anovulation. The use of L-thyroxine is not helpful in treating euthyroid patients for infertility, menstrual irregularity, or the premenstrual syndrome.29,30 In evaluating the thyroid status of the pregnant woman, the level of TSH is probably the best indicator of changes in thyroid function. Because radioiodine will readily cross the placenta and can cause fetal hypothyroidism, tests involving ra- dioiodine administration to the mother are contraindicated in pregnancy.19 When hypothyroidism is diagnosed during pregnancy, L-thyroxine therapy should be instituted promptly to increase the chances for a normal pregnancy. Although it has been thought that little L-thyroxine would cross the placenta,19 it appears that L-thyroxine will cross the placenta in modest amounts,31 at least early in pregnancy. Women who have required thyroid hormone therapy prior to pregnancy should continue with such therapy throughout the pregnancy. How- ever, recent evidence indicates that the hormone dose needs to be increased during pregnancy, even though adequate replacement had been given before conception.31 It is advisable to monitor the serum TSH concentration at least once during each trimester to ensure that an adequate dose is received. Thyroid disease during and after pregnancy is discussed in detail in chapter 89. Some myxedematous women will present with amenorrhea and galactorrhea and elevated serum prolactin concentrations.19 Thus, thyroid evaluation should be an essential part of the work-up in any person with galactorrhea. If hypothyroidism is the cause, the amenorrhea and galactorrhea and elevated serum prolactin will disappear promptly with thyroxine therapy.32 There is an increased incidence of Hashimoto's thyroiditis in individuals with 's syndrome,33 and, although a chromosomal linkage between autoimmtme disease and the X- chromosome has been suggested, this has not been confirmed.34 Inherited abnormalities in serum thyroxine-binding globulin (TBG) are X-linked, and patients with 's syndrome may ,have low serum TBG values.35 Women with hypothyroidism have decreased metabolic clearance rates of androstenedione and estrone and increased peripheral aromatization.36 The ratio of 5a/5B metabolites of androgens is decreased in hypothyroid women, and there is an increase in the excretion of estriol and a decrease in the excretion of 2-oxygenated estrogens.37 In summary, hypothyroidism in girls can cause alterations in the pubertal process; this is usually a delay, but occasionally it can result in pseudoprecocious puberty. In mature women, hypothyroidism usually is associated with abnormal menstrual cycles, especially anovulatory cycles, and an increase in fetal wastage. HYPOTHYROIDISM IN THE MALE EPRODUCTIVE SYSTEM The normal development and physiology of the male reproductive system has been described in chapter 47. Although less common in men than in women, hypothyroidism, induced or spontaneous, affects the male reproductive tract in a number of ways depending, in part, on the age of onset. Animal Studies The fetal thyroid starts functioning about the same time as the gonads.38 Although thyroid hormones play role in sex differentiation and gonadal maturation in fish and amphibians,39 they do not appear to be necessary for the normal development of the reproductive tract in mammals. 1 However, hypothyroidism, induced or occurring soon after birth, is associated with a marked delay in sexual maturation and development.40 When rats are made hypothyroid with propylthiouracil administered from birth to 24 to 26 days of age, testicular size is decreased, Sertoli cell differentiation is retarded, and the time of Sertoli cell proliferation is prolonged.4].42 As these rats become older and euthyroid, then the testis size, Sertoli cell number, and sperm production are all increased.41, Leydig cell numbers are increased but testosterone secretion per cell is decreased, although total testosterone secretion remains the same as controls.43 FSH and LH levels tend to remain low throughout treatment and recovery periods, whereas inhibin levels are elevated.41 However, if hypothyroidism persists untreated, there is an arrest of sexual maturity with absent libido and ejaculate.44 The interstitial cells of the testis are reduced in number and the arrested growth of the accessory male sex organs indicates a decrease in the production of testosterone.44 The longer the hypothyroidism persists, the greater the degree of damage to the testes,44 although genetically induced hypothyroidism in male mice is associated with normal fertility .45 In the adult ram, hypothyroidism is associated widl a decrease in testosterone concentration but normal spermatogenesis.46 In the mature male rat, the induction of hypothyroidism has little effect on the pathology of the testes, sperlllatogenesis, or serum testos- terone concentrations.47 Thus, it would appear that hypothyroidism can affect the immature, but not the mature, testis. Human Studies and Clinical Aspects The development of hypothyroidism in the male fetus does not appear to affect the reproductive system. Cretins are usually born with a normally developed reproductive tract. The presence of hypothyroidism in the prepubescent years usually results in a delay of sexual maturation and of the whole pre-pubertal process, which can be overcome by the administration of adequate doses of thyroxine. However, in some instances, hypothyroidism can result in precocious pseudopuberty marked by the early development of external genitalia, but without the appearance of axillary and pubic hair. 48 This syndrome probably results from an increased secretion of gonadotropins along with TSH from the enlarged pituitary.48 In men, hypothyroidism has been suggested as a cause of infertility,49 but there is considerable disagreement with this suggestion. 50 If an infertile man is found to be hypothyroid, one should suspect secondary hypothyroidism and pituitary disease rather than primary myxedema, and there is no reason to treat infertile euthyroid men with thyroid hormone.50 In hypothyroid men, testicular size and potency may be normal and, despite early reports of defective spermatogenesis in hypothyroidism, 51 semen analysis is usually normal.52 Wortsman and colleagues reported that myxedema was often associated with infertility and impotence, but in this report the impotence did not improve when the men became euthyroid.49 In addition, there was a decrease in serum testosterone and free testosterone and, in the men who were not over-weight, an increase in sex hormone-binding globulin. It should be noted that sex hormone-binding globulin levels have also been reported as both decreased53 and normal 54 in hypothyroid men. Many men with hypothyroidism do note a decrease in libido, but this is probably a nonspecific disease-related complaint, which disappears when the euthyroid state is achieved with thyroid replacement therapy. Variations in testis size and histology have been noted in autopsy material,55,56 and De La BaIze and coworkers 51 noted Leydig cell hyperplasia and tubular hyalinization. There is a marked decrease in the 5a/5B ratio of the metabolites of androstenedione and testosterone, which is the reverse of that seen in hyperthyroidism 57 In summary, although hypothyroidism in boys frequently interferes with the normal pubertal process, the development of hypothyroidism in men has a less clear-cut effect on the reproductive system. References - not thoroughly checked 1. Hopkins PS, Thorburn GD. The effects of foetal thyroidectomy on the devel2. Leathem JH. Extragonadal factors in reproduction. In: Lloyd CW, ed. Recent progress in the endocrinology of reproduction. New York: Academic Press, 1959:179 3. Leathem]H. Role of the thyroid. In: Balin H, Glasser S, eds. Re- productive biology. Amsterdam: Excerpta Medica, 1972:23 4. Hayles AB, Cloutire MD. Clinical hypothyroidism in the young— a second look. Symp Endocr Disorders 1972:56:871 5. Scow RO, Simpson ME. Thyroidectomy in the newborn rat. Anat Rec 1945;91:209 6. Ortega E, E, Ruiz E. Activity of the hypothalamo- pituitary ovarian axis in hypothyroid rats with or without tri- iodothyronine replacement. Life Sci 1990;46:391 7. Takacs-Jarrett M, Broot BC. Steroid secretion by follicles and cysts from the hypothyroid, hCG-treated rat. Sac Experimental BioI Med 1994;207:62 8. Vriend J, Bertalanffy FD, Ralcewicz TA. The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in fe- male Syrian hamsters. Bioi Reprod 1987;36:719 9. Maqsood M. Thyroid functions in relation to reproduction of mammals and birds. Bioi Rev 1952;27:281 10. Bonet B, Herrera E. Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat. Endocrinology 1991;129:210 11. Rao PM, PandaJN. Uterine enzyme changes in thyroidectomized rats at parturition. J Reprod FertiI1981;61:109 12. Nesbitt REL, Abdul-Karim RW, Prior JT, TF, Rourke JE. Study of the effect of experimentally induced endocrine insults upon pregnant and nonpregnant ewes. m. ACfH and propyl- thiouracil administration and the production of polycystic ovaries. Fertil Steril1967;18:739 13. Ruh MF, Ruh TS, Klitgaard HM. Uptake and retention of estro- gens by uteri from rats in various thyroid states. Proc Soc Bioi Med 1970;134:558 14. Kirkland JL, Gardner RM, Mukku VR, Akhtar M, Stancel GM. Hormonal control of uterine growth: The effect of hypothy- roidism on estrogen-stimulated cell division. Endocrinology 1981;108:2346 15. Moenter SM, Woodfill CJI, Karsch FJ. Role of the thyroid gland in seasonal reproduction: Thyroidectomy blocks seasonal suppres- sion of reproductive neuroendocrine activity in ewes. En- docrinology 1991;128:1337 16. Dawson A. Thyroidectomy progressively renders the reproduc- tive system of starlings (Sturnus vulgaris) unresponsive to changes in daylengtll. J EndocrinoI1993;139:51 17. Kendle F. Case of precocious puberty in a female cretin. Br Med J 1905;1:246 18. Van Wyk J, Grumbach MM. Syndrome of precocious menstrua- tion and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap pituitary feedback. J Pediatr 1960;57:416 19. R, Reid RL. Thyroid disease and reproductive dysfunc- tion: a review. Obstet GynecoI1987;70:789 20. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. AmJ Obstet GynecoI1989;160:673 21. Higham]M, Shaw RW. TIle effect of thyroxine replacement on menstrual blood loss in a hypothyroid patient. Br J Obstet Gy- naecol 1992;99:695 22. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimu- lation syndrome associated with hypothyroidism. Am J Obstet GynecoI1989;160:1220 23. Goldsmith RE, Sturgis SH, Lerman J,. Stanbury JB. The menstrual pattern in thyroid disease. J Clin Endocrinol Metab 1952;12:846 24. Wakim AN, Polizotto SL, Buffo ML, Marrert;> MA, Burholt DR. Thyroid hormones in human follicular fluid and thyroid hor- mone receptors in human granulosa cells. Fertil Steril 1993;59:1187 25. Channing CP, Tsai V, Sachs D. Role of insulin, thyroxine and cor- tisol in luteinization of porcine granulosa cells grown in chemi- cally defined media. Bioi Reprod 1976;15:235 26. Gerhard I, Becker T, Eggert-Kruse W, Klinga K, Runnebaum B. Thyroid and ovarian function in infertile women. Hum Reprod 1991;6:338 27. LE, Leveno KJ, Cunningham FG. Hypothyroidism compli- cating pregnancy. Obstet Gynecol1988;72:108 28. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JR. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993;81:349 29. Nikolaj TF, Mulligan GM, Gribble RK, Harkins PG, Meier PR, RC. Thyroid function and treatment in premenstrual syn- drome.J Clin Endocrinol Metab 1990;70:1108 30. Roti E, Minelli R, Gardini E, Braverman LE. The use and misuse of thyroid hormone. Endocr Rev 1993;14:401 852 31. Burrow GN, Fisher DA, Larsen PRo Maternal and fetal thyroid function. N EnglJ Med 1994;331:1072 32. CRW, Forsyth lA, Besser GM. Amenorrhea, galactorrhea and primary hypothyroidism with high circulating levels of pro- lactin. Br MedJ 1971;3:462 33. Van Campenhout J, Van J, Antaki A, Rasio E. Diabetes mellitus and thyroid autoimmunity in gonadal dysgenesis. Fertil Steril 1973;24:1 34. Vallotton ME, Foibes AP. Autoimmunity in gonadal dysgenesis and Klinefelter's syndrome. Lancet 1967;1:648 35. Refetoff S, Selenkow HA. Familial thyroxine-binding globulin deficiency in a patient with 's syndrome (XO). N Engl J Med 1968;278:1081 36. Longcope C, Abend S, Braverman LE, Emerson CR. Androstene- dione and estrone dynamics in hypothyroid women. J Clin En- docrinol Metab 1990;70:903 37. Gallagher TF, Fukushima DK, Noguchi S, et al. Recent studies in steroid hormone metabolism in man. Recent prog Horm Res 1966;22:283 38. Saenger P. Abnormal sex differentiation. J Pediatr 1984;104:1 39. Lynn WG. The thyroid gland and reproduction in cold blooded vertebrates. Proceedings of the Fifth Mid-West Conference Thy- roid 1969;17 40. Palmero S, de Marchis M, Gallo G, Fugassa E. Thyroid hormone affects the development of Sertoli cell function in the rat. J En- docrinoI1989;123:105 41. Kirby JD, Jetton AE, Cooke PS, et al. Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced in- crease in adult testicular size and sperm production in the rat. Endocrinology 1992;131:559 42. Van Haaster LH, de Jong PH, Docter R, De Rooij DG. The effect of hypothyroidism on Sertoli cell proliferation and differentia- tion and hormone levels during testicular development in the rat. Endocrinology 1992;131:1574 43. Hardy MP, Kirby]D, Hess RA, Cooke PS. Leydig cells mcrease their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 1993;132:2417 44. Gomes WR. Metabolic and regulatory hormones influencing testis function. In: AD, Gomes WR, Vandemark NL, eds. The testis. Vol III. Influencing factors. New York: Academic Press, 1970:67 45. Chubb C, Henry L. The fertility of hypothyroid male mice. J Re- prod Fertil1988;83:819 46. dIandrasekhar Y, Holland MK, D'Occhio Mj, Setchell BP. Sper- matogenesis, seminal characteristics and reproductive homlone levels in mature rams with induced hYPQthyroidism and hyper- thyroidism. J EndocrinoI1985;105:39 47. Weiss SR, Burns JM. The effect of acute treatment with two goitrogens on plasma thyroid hormones, testosterone and testic- ular morphology in adult male rats. Comp Biochem Physiol (A) 1988;90A:449 48. Castro-Magana M, Angulo M, Canas A, Sharp A, Fuentes B. Hy- pothalamic-pituitary gonadal axis in boys with primary hypothy- roidism and macroorchidism. J Pediatr 1988;112:397 49. Wortsman J, Rosner W, Dufau ML. Abnormal testicular func- tion in men with primary hypothyroidism. Am J Med 1987; 82:207 50. Steinberger E. The thyroid gland in male infertility. In: C-R, Mastroianni LJr, Amelar R, Dubin 1, eds. Current therapy of infertility 1982-1983. St Louis: CV Mosby, 1982:15 51. De La BaIze FA, Arrilloga F, Mancini RE. Male hypogonadism in hypothyroidism: a study of six cases. J Clin Endocrinol Metab 1962;22:212 52. Griboff S. Semen analysis in myxedema. Fertil Sterill962;13:436 53. Cavaliere H, Abelin N, Medeiros-Neto G. Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. J AndroI1988;9:215 54. De Nayer P, Lambot MP, Desmons MC, Rennotte B, Malvaux P, Beckers C. Sex homlone-binding protein in hyperthyroxinemic patients. A discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab 1986;62:1309 55. s RC, son SD. Pathologic changes in adult myxedema: survey of 10 necropsies. j Clin Endocrinol Metab 1957;17:1354 56. Marine D. Changes in the interstitial cells of the testis in Gull's disease. Arch PathoI1939;28:65 ____________________________ Author: Sheldon S. StofIer. MD Date Published: 01-Jan-1982 Publication: POSTGRADUATE MEDICINE. VOL 72/NO 2/AUGUST 1982 Title: Menstrual disorders and mild thyroid insufficiency Intriguing cases suggesting an association Category: reproductive Keywords: reproductive, problem, StofIer, Menstrual, disorder, mild, thyroid, insufficiency, case, suggest, association, pathology, patient, treat, levothyroxine, hypo, hyper, TSH, TRH Text: Should patients with menstrual dysfunction but without obvious uterine pathology be considered for thyrotoxin-releasing hormone (TRH) testing? In several cases described here. an apparent relationship between menstrual disturbance and minimal thyroid insufficiency was documented by the patients' dramatic response to treatment with levothyroxine. The association of overt hypothyroidism or hyperthyroidism with menstrual disturbance and infertility is well known.15 However, menstrual disturbance may also be related to minimal thyroid insufficiency, as the following cases suggest. The past ten years have brought enonnous advances in the ability to diagnose mild thyroid dysfunction. The introduction of serum thyroxine and serum thyroid -stimulating hormone (TSH) radioimmunoassays has increased the sensitivity and specificity of thyroid function testing. The serum TSH assay has been shown to be a sensitive indicator of diminished thyroid functional reserve. since TSH levels become elevated before circulating serum thyroxine levels fall below the normal range 6, Thyrotropin-releasing hormone (TRH) is a simple tripeptide nonnally found in the hypothalamus. Its availability in synthetic fonn, protirelin (Thypinone, Relefact TRH), has provided a convenient provocative test of pituitary TSH reserve and has further extended the sensitivity of thyroid testing. In fact, this TRH test is so sensitive that results may be markedly abnormal in patients with no signs or symptoms of thyroid disease.6 Patients with minimal impairment of thyroid functional reserve who have normal serum thyroxine and normal baseline serum TSH levels may have an augmented TSH response to TRH administration.6 76 76 Table 1. Results of thyroid function studies in four patients with menstrual disturbance treated by levothyroxine therapy Case Time of testing Thyroid function study FTI* Baseline TRH:+ TSHt 1 Initial study 2.2 6.0 58.0 After26mo of treatment 2.9 3.0 11.7 2 Initial study 1.9 7.1 57.3 After 6 mo of treatment 3.5 1.6 1.8 3 Initial study 1.7 Two years later 2.1 7.2 52.9 After 3 mo of treatment 2.0 1.2 After 21 mo of treatment 2.6 2.8 14.3 4 Initial study 1.8 9.3 >80 After2 mo of treatment 3.8 3.0 6.1 After 14 mo of treatment 1.7 16.4 >80 After 2 mo of increased 3.6 2.5 2.5 dosage * Free thyroxine index (total T4 x T3 resin uptake). normal range 1.4-4.0 +Thyroid-stimulating hormone by radioimmunoassay, normal <8.0 uU/mc tThyrotropin-releasing hormone test (serum TSH rise 20 min after administration of 100 ug TRH), normal range 2-20 uUI ml 80 ...... Discussion In the past, when thyroid test-ng was nonspecific, inaccurate, and insensitive, desiccated thyroid tablets were often given empirically to women with menstrual dysfunction and/ or infertility. Some of these patients may have improved, reinforcing this unscientific and currently unjustifiable approach. At least a portion of these women may have actually had subclinical, and at that time undetectable, thyroid insufficiency. ...... Recently, I encountered a 32 year-old patient with evidence of very mild thyroid insufficiency who had undergone hysterectomy four years before because of troublesome hypermenonorrhea The patient had a diffuse goiter 11/2 times normal size, and antimicrbsomal antibodies were positive at 1:6,400 dilution. Serum FTI was 1.5, baseline serum TSH was 6.3 µU/m1, and serum TSH 20 minutes after TRH administration was 60.7 µU/m1. The pathology report revealed a normal-sized uterus With a predominantly proliferative endometrium and a normal myometrium. Although mild thyroid dysfunction cannot be proven responsible for this patient's abnormal menstrual bleeding, one wonders if TRH testing could have avoided the need for hysterectomy in this case and perhaps in similar cases. ...... 82 ...... Recommendations Based on my experience, I would recommend that patients \vith long- standing menstrual dysfunction without obvious uterine pathology be considered for TRH testing. Such testing would be especially fruitful in patients with goiter, high-nrmal baseline serum TSH value, or family history of thyroid disease. I would certainly not encourage empirical use of thyroid hormone in such a patient population without appropriate testing. Because mild thyroid insufficiency is so easily treated, TRH testing and atrial of thyroid hormone therapy, if .indicated, should be considered in difficult cases of menstrual dysfunction prior to hysterectomy. Summary Three cases of menstrual disturbance possibly related to minimal thyroid insufficiency are reported. In all cases, tltyrotropin- releasing hormone testing was sensitive enough to detect evidence of tltyroid abnormality .Without exception, treatment with levothyroxine caused a dramatic end to menstrual difficulty. In two of these cases, levotltyroxine tlterapy was discontinued and the menstrual abnormality returned. Resumption of levotltyroxine treatment led to prompt retum of normal menstruation. A fourth case is presented which suggests tltat placebo effect alone is probably not responsible for the observed menstrual improvement. It is possible that minimal thyroid insufficiency can lead to marked menstrual disturbance. References I. Goldsmith RE. Sturgis SH. Lennan J. et a!. The menstrual pattern in thyroid disease J Clin Endocrinol Metab 1952 12: 846-55 2. Distiller LA. Sage1 J. Morley JE. et a!. Assess ment of pituitary gonadotropin reserve using luteinizing hormone releasing hormone (LRH) in states of altered thyroid function J Clin Endocrinol Metab 1975:40, 512-15 3. Keye WR. Yuen BH. KnopfRF. et a!. Amenorrhea yperprolactinemia, and pituitary enlargement secondary to primary hypothyroidism Obstet Gyneco 1976:48,697-702 4. Van Wyk JJ. Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism an example of hormonal overlap in pituitary feedback J Pediatr 1960:57,416-35 5. Tolis G. Hoyte K. McKenzie JM. et al. Clinical.biochemical and rndlologic reversibility of hyperprolactinemic galactorrhea.amenorrhea and abnorma sella by thyroxine in a patient with primary hypothyraidisrn Am J Obstet Gynecol 1978:131, 850-2 6. Ingbar SH. Woeber KA. The thyroid gland In: Willams R. ed, Textbook of endocrinology 6th ed Philadelphia WB Saunders, 1981: 117- 247 7. Buchanan GC. Tredway DR. Pittard JC. et a!.Gonadotropin secretion and hypothyroidism Obstet Gynecol 1977: 50,392-6 S. CoUu R. Abnormal pi tui tary hormone response to thyrotropin- reieasing hormone an index. of central nerve system dysfunctlon In Tolis G, Labrle, F JB, et al. eds Cllnical neuroendocrinology a pathophysiological approach New York Raven Press 1979: 129-37 9. Snyder PJ. s LS. Utige RD et al. Thyroid hormone inhibitlon of the prolactin response to thyrotropin-releasing hormone J Clin Invest 1973: 52,2324-9 10. Tolls G. Prolactin physiology and pathology In: Krieger DT JC eds Neuroendocrinology Sunderland. MA Sinauer Assoc, 1980: 34,322-8 11. Powers JM. Block MB. Primary hypothyroidlsm with reversible hypeprolactinemia and pituitary enlargement Ariz Med 1989:37, 256-8 12. Stoffer SS. McKee1 DW Jr. Randall RV, et a!. Pituilary prolactin cell hypetplasia with autonomous prolactin secretlon and primary hypothytoidism Fertil Steril 1981: 36,682-5 __________________ Author: Luoto R Date Published: 27-Jun-1997 Publication: Int J Epidemiol 1997 Jun;26(3):476-83 Title: Hysterectomy and subsequent risk of cancer. Category: reproductive Keywords: Luoto, Hysterectomy, subsequent, risk, cancer, Elevate, papillary, thyroid, follow, reproductive, endocrinological, cause, high, breast, peri, retrospective, study, menopause, total, pre Text: BACKGROUND: The objective of this retrospective cohort study was to assess the effect of hysterectomy on subsequent risk of cancer among 25,382 hysterectomized and a similar number of non- hysterectomized control women, registered in 1963-1976 in the Mass Screening Registry (MSR). METHODS: Cancer cases were obtained from the Finnish Cancer Registry (FCR) and standardized incidence ratio (SIR); the expected number of cases based on cancer incidence rates of the Finnish female population in 1967-1993, was used. Relative risk (RR) was calculated as SIR among the hysterectomized relative to non-hysterectomized women, adjusted for follow-up, education and parity. RESULTS: The RR estimates of non-genital cancers among women with any hysterectomy were approximately 5% higher than in the non- hysterectomized cohort. Relative risks of rectal cancer (RR = 1.4, 95% confidence interval [CI]: 1.0-1.8) and thyroid cancer (RR = 2.1, 95% CI; 1.5-3.1) were significant and largest among women who had undergone total hysterectomy pre- or perimenopausally. Relative risk estimates of breast cancer were close to unity. CONCLUSIONS: Hysterectomy is not associated with any substantial protective or promoting effect on cancers in general. Elevated risk of papillary thyroid cancer following hysterectomy is biologically plausible, as there are reproductive and endocrinological causes of thyroid cancer. National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland. PMID: 9222770 [PubMed - indexed for MEDLINE] _____________________ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 19, 2005 Report Share Posted March 19, 2005 I don't believe coffee is a problem. Have you ever noticed that people are willing to give up coffee for their fibroids, but won't give up chocolate even though it has some bad things in it that are just as bad as coffee? I started to think, after being on fibroid newsgroups for three years, that people think that if it's good and give pleasure, then somehow it's bad for fibroids. Sort of like fibroids are caused by sin and if we sacrifice those things we love to be healed. The other notion people seemed to have a lot is that fibroids are the cause stuck energy and emotional issues that are not worked out. This one is one of those classic " blame the victim " notions. You are the cause of your own illness and if you can somehow fix your sick mind or maybe " find God " or do some peace work, you will be cured and your punishment removed. I suppose coffee does increase adrenal output and this might raise cortisol and high cortisol tends to increase estrogen. But, I don't know how you could say coffee is any worse than a serving of beans or nuts or drinking out of plastic or spraying weeds in your yard with pesticides or eating meat of animals given growth hormone and on and on. Where do you draw the line? The biggest cause of fibroids in my book is low thyroid, combined with genetics, and stress, which plays into the thyroid problems. A big study was done in Italy on eating habits and fibroids. The only thing they could find that correlated was the amount of red meat eaten. The correlation was very weak at best and did not really prove it unequivically. Tish ______________________ Here are some things I have collected on this topic. ______________________ But menstrual irregulaities are not the only hrmful affect low thryoid has on the uterus. A lack of thyroid greatly enhances the growth of uterine fibroids as well. If a woman is on sufficient amounts of thyroid the further growth of uterine fibroids usually will be blocked and frequently they will start shrinking. Besides uncontrolled bleeding, the major reason that women have hysterectomies is symptomatic uterine fibroids which can cause discomfort and contribute to excessive bleeding. Hypothyroidism also increases the incidence of uterine cancer which is the reason behind most the remaining hysterectomies. So thyroid has an almost magical impact on many of the woes associated with womanhood; it takes them away. (Page 117) And as mentioned elsewhere, there is a close relationship between the binding sites of thyroid and the binding sites of estrogen, so the function of thyroid and estrogen are intertwined in subtle ways. (Page 116) " Thyroid, Guardian of Health " by Philip G. Young, MD, Trafford Publishing, , BC., Canada, 2002 __________________________ Fibroid tumors have been rare in hypothyroid women who have been maintained on adequate thyroid therapy. It is possible to produce fibroids in experimental animals by injection of estrogens, and there is evidence of excess of estrogens in hypothyroid women. In hypothyroidism, there is increased activity of the pituitary gland aimed at trying to stimulate the thyroid to produce more hormone secretions, and the increased pituitary activity may spill over to affect ovaries and increase their estrogen output. (Page 133) " Hypothyroidism: The Unsuspected Illness " by Broda O. , M.D. and Lawrence Galton, Harper & Row, Publishers, New York, 1976 ________________ [Diagnosis of thyroid function in uterine myomatosis] [schilddrusenfunktionsdiagnostik bei Myomatosis uteri.] Zentralbl Gynakol 1989;111(1):47-52 (ISSN: 0044-4197) Lange R; Meinen K Gynakologisch-Geburtshilflichen Abteilung, St. Lukas Klinik Solingen. A correlation between thyroid disease and uterine myoma has been discussed till the fourth decade of this century. Since then, this possible connection was given no further notice. We examined 79 women needing a hysterectomy for various reasons regarding myometrial histology, thyroid function and thyroid antibodies. The patient group bearing myomas showed significantly more frequent (23%) pathological TRH/TSH stimulation tests results than the control group (3.7%, p = 0.0543). 10 of 22 patients with myomas had microsomal and/or thyroglobin antibodies, compared with none in the control group (n = 17, p = 0.0019). Therefore regarding these results a connection between thyroid disease and uterine myoma should undergo a more detailed examination. ______________________________ Part B - Oestrogen, Progesterone & Testosterone The hormones that keep us male and female are crucially affected by thyroid and adrenal function; and in turn can effect the proper functioning of the thyroid itself. So let us see where they fit in. Since my approach to metabolic problems is holistic, we have to ask if thyroid and adrenal insufficiency may be altered or worsened by deficiencies elsewhere. The answer is of course, yes. Since a state of lowered metabolism means that nothing really works as it was designed to, it follows that other hormone producing glands may not do their job properly either. It is a bit like an extraordinarily complex piece of electrical machinery, designed for 240 volts, running on 210 volts. It runs, but the lights look a bit dim and flicker a bit. Bringing up the voltage - gently - will get everything working again. So far as other components of the endocrine system go, we must be prepared for partial recovery only, and supplementation may well be indicated elsewhere as well. We are talking mostly about sex hormones here, and the effects of the menopause on both sexes. We have learnt already how important the adrenal corticosteroids are in the maintenance of the body's normal health; the male and female sex hormones, which are of course also steroids, are just as extraordinarily important in their own right. (It may have perhaps surprised you to realize that the whole body, most especially many of its hormones, is based on the steroid molecule. The use of the word " steroid " has been denigrated in the popular mind as being potentially, if not actually, dangerous, and this is a complete distortion. The contraceptive pill, for which millions of prescriptions are written weekly, is based on two steroids and few doctors and few patients are especially concerned that they do in fact belong to the great family of steroids). We will start with the female menopause, which will be hastened or worsened by a low thyroid/adrenal state. Literally, the menopause means " the last period " . For some women this is an abrupt thing, there one month and gone the next. Very often the process is rather more protracted than this; the periods start lengthening and sputter about; they may become heavy with pain and floods, or become very light and irregular. And menstrual problems, with heavy irregular periods, are certainly associated with low thyroid. So we need to have a look at the whole business, so that we can decide to intervene if necessary while treating the metabolic problems. Women actually produce three different sex hormones, oestrogen (which has three different forms: oestradiol, oestrone and oestriol), progesterone and testosterone. You thought testosterone was a male hormone, didn't you. Well, it is; but women produce it too - though less than men of course. (The reverse is also the case.) In general oestradiol, the main oestrogen, comes from the ovaries, the other two from the adrenals, directly or indirectly, and more after the menopause. The way it all works is this. As the menarche (the start of periods) approaches, the ovaries start to produce oestrogen and under the influence of a pituitary hormone, the Follicle Stimulating Hormone (FSH), an ovarian follicle (of which there are many hundreds containing egg cells waiting their time) matures an ovum which surfaces about mid cycle and is released. It finds its way into one of the fallopian tubes (right or left, depending on which ovary produced the ovum) where it may or may not be fertilized. The place from where it was released on the ovary undergoes a change to produce the Corpus Luteum or " Yellow Body " . This structure begins to produce under the influence of Luteinizing Hormone (LH) from the pituitary, another hormone, progesterone. This prepares the lining of the womb for implantation if the ovum is fertilized. Oestrogen and progesterone are produced together for the second half of the cycle; and then the supply is cut off abruptly which starts off the menstrual period. Hypothyroidism can affect this process in several ways. To start with, a low thyroid state affects the onset of the first period, oddly enough in two opposing ways. The first period may come unusually early at 8, 9 or 10 years old; or, it may come unusually late, 15, 16 or 17 years old. Periods starting abnormally like this should raise a suspicion about the thyroid at once. The periods may be abnormal in other ways. They may be exceedingly painful with collapse and prostration of the unfortunate girl; they may be very heavy or very light or come at irregular times. There may be premenstrual tension to make life miserable. These problems may occur at any time of life, but may sort themselves out a bit after having children. Then in the later thirties and early forties it all goes wrong and flooding and terrible PMT may ruin things so badly that relationships suffer. The gynecologist may not think of thyroid dysfunction as a cause and the ladies then become the target of various synthetic hormone combinations, which may or may not bring relief. It is at this point, of course, that hysterectomy becomes the treatment choice, and worn out with it all, the unhappy sufferer consents to surgery. Relief from the terrible periods may well justify the hysterectomy for the patient; but it may have missed the point altogether. As I said earlier, hysterectomy is very likely to affect thyroid activity. There seems to be a chemical dialogue between the womb and the thyroid; and interference - including sterilization, termination, or even a D&C, seems to damage thyroid function for many. The weight gain, which nearly always occurs, is not due to comfort eating while grieving for one's lost fertility, but because thyroid activity may be further damaged. This, and the other symptoms of a running down of thyroid activity, is a heavy price to pay for an operation for which one out of every three, at least, wasn't necessary and could have been avoided if thyroid status had been properly assessed and treated. The other worry which besets women at this time of their lives is premenstrual tension (PMT) or as the Americans call it (PMS) premenstrual syndrome. Some doctors won't have that this occurs at all. I remember reading an authoritative article by a lady doctor who discounted it completely; one just wonders what planet she came from. Not only is it a very real problem; if anything it is getting worse. Although a number of causes have been cited, it seems clear that it is associated with an imbalance between the oestrogen and progesterone production. This last, may drop anyway with the general loss of viability of the ovum and the corpus luteum; but it is much worse with deficient thyroid hormone. Throughout my experience with low thyroid, I have been staggered to find that some women lose their PMT within a month or so of starting their thyroid supplementation - simply the result of improved progesterone production. Where progesterone production in the mid thirties and forties has not been improved by thyroid supplementation, very thoughtful consideration must be given to the provision of progesterone supplementation. The standard way of doing this is by the use of a group of artificial progesterones, which are called progestogens and the synthetic hormone Norithesterone is an example. While these may well be helpful for some women, they have a number of side effects which have made them less and less popular; nevertheless, an alternative must be sought. As oestrogen dominance brings with it its own problems of bloating, weight gain and increased risk of cancer, a progesterone supplementation is essential. Of increasing popularity nowadays is the use of natural progesterone, which is actually extracted from plants and is incorporated in creams which may be simply rubbed into the skin daily. Although establishment thinking is, as might be expected, somewhat suspicious of the natural product, favoring the artificial, very many thousands of women are greatly benefiting from transdermal progesterone (see Appendix D). Another worrying result of a reduction in thyroid function is a reduction of red blood cell production; many people are troubled by a refractory anaemia (when it is unresponsive to treatment), which adds to their general lack of well-being and exhaustion. How much worse is it then, when heavy prolonged periods are added to the problem.. . Iron, folic acid and vitamin C would seem to be essential, especially in the early phases of treatment. A most alarming gap in the management of infertility, is the failure to realize that a prime and a gravely neglected cause is hypothyroidism. It is obvious that there are several ways the healthy ovum can be affected: its production, its maturation, proper fertilization and implantation....... (Pages 135 - 139) " The Great Thyroid Scandal and How to Survive It " by Dr. Barry Durrant-Peatfield MB BS LRCP MRCS, Barons Down Publishing, London, 2002, ___________________________ Ginecol Obstet Mex. 1969 Dec;26(158):777-85. [Report on the relation between limited hypothyroidism and uterine fibromyomatosis] [Article in Spanish] Gutierrez JT. PMID: 5408031 [PubMed - indexed for MEDLINE (Paper can be purchased from PubMed) _____________________ Akush Ginekol (Mosk). 1988 May;(5):46-50. [The reproductive system of patients with disordered thyroid function] [Article in Russian] Sosnova EA. PMID: 3177773 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ___________________________ J Assoc Physicians India. 1993 Feb;41(2):88-90. Comment in: J Assoc Physicians India. 1993 Nov;41(11):761-2. Hypothyroidism presenting with polycystic ovary syndrome. Sridhar GR, Nagamani G. Endocrine & Diabetes Centre, Visakhapatnam. During a 30 months period, two women of primary hypothyroidism (2/13; 1.04%) presented with features of polycystic ovary syndrome (PCOS). In hypothyroidism, sex hormone binding globulin levels are decreased; increased conversion of androstenedione to testosterone, and aromatization to estradiol are present, all these being an exaggeration of biochemical changes characteristic of PCOS. Besides, metabolic clearance rates of androstenedione and estrone, the putative mediators of PCOS, are reduced. Hypothyroidism can either initiate, maintain or worsen the syndrome. Correction of hypothyroidism when present, would therefore form an important aspect in the management of infertility associated with PCOS. Publication Types: Case Reports PMID: 8053991 [PubMed - indexed for MEDLINE] __________________ Pediatr Akus Ginekol. 1968 Sep-Oct;5:55-8. [Function of thyroid gland in uterine fibromyoma] [Article in Ukrainian] Sol's'kii IaP, Chizhova PS, Ivaniuta PI. PMID: 5743398 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _______________________ Akush Ginekol (Mosk). 1970 Oct;46(10):24-7. [Functional status of the thyroid gland in patients with uterine myoma] [Article in Russian] Vasilevskaia LN, Kotliarov EV. PMID: 5519731 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _________________ Ginecol Obstet Mex. 1974 Jun;35(212):657-80. [Edocrinal study of uterine fibromyoma] [Article in Spanish] Nava y R. PMID: 4138171 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ____________________ Akush Ginekol (Mosk). 1967 Oct;43(9):17-21. [Adrenal cortex and thyroid gland function in patients with myoma of uterus] [Article in Russian] Slepov MI, Novouspenskaia IE. PMID: 5607969 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ________________ Author: GRIFF T. ROSS, M.D., Date Published: 01-Jan-1958 Publication: Journal of Clinical Endocrinology and Metabolism 18: 492-500, 1958 Title: SEVERE UTERINE BLEEDING AND DEGENERATIVE SKELETAL-MUSCLE CHANGES IN UNRECOGNIZED MYXEDEMA Category: reproductive Keywords: reproductive, problem, ROSS, SEVERE, UTERINE, BLEED, DEGENERATIVE, SKELETAL, MUSCLE, CHANGE, UNRECOGNIZED, MYXEDEMA, treat, women, menstruation, severe, anemia, normal, desiccated, thyroid Text: p 492 ABSTRACT Two cases of severe uterine bleedng associated with unrecognized myxedema (hypothyroidism) are reported. Degenerative changes in skeletal muscles were suggested by the results of electromyographic studies and demonstrated by biopsy of a muscle prior to treatment in one patient. The uterine bleeding stopped promptly and a normal menstrual cycle was re-established in both patients after treatment with desiccated thyroid. DISTURBANCES in thyroidal function in premenopausal women are often associated with abnormalities of menstruation. Either menorrhagia or amenorrhea may develop in patients with spontaneous or postoperative myxedema. However, when amenorrhea occurs in a premenopausal women with the secondary hypothyroidism the diagnosis of hypopituitarism should be considered and excluded. In his book, Means stated: " Menorrhagia may be sufficiently impressive in ordinary myxedema so that in several cases that have come to our attention patients have actually had a dilation and curettage for it when all they needed was desiccated thyroid for treatment. " We are reporting 2 cases of profuse uterine bleeding with severe anemia secondary to unrecognised primary myxedema, in which prompt cessation of uterine bleeding and restoration of normal menstrual cycles followed the oral administration of desiccated thyroid. Significant degenerative changes in the skeletal muscles were suggested by the results of electromyography and were demonstrated by muscle biopsy prior to treatment in one of these patients. p 494 .. ....COMMENT Both these patients were referred for consideration of surgical treatment for intractable profuse uterine bleeding. Severe menorrhagia lasting from p495 six to ten days had been present during the six months preceding the admission of the first patient to the hospital. After the clinical recognition of myxedema, it was realized that the bleeding might be due to the hypothyroidism. For this reason, operation was deferred until the patient could be restored to euthyroid state. After five days of oral treatment with desiccated thyroid, the uterine bleeding ceased. The menstrual pattern subsequently returned to normal with regard to periodicity and flow. Despite the fact that the second patient had noted intermenstrual spotting for many years, the myxedema in all probability began after her last pregnancy in 1950. There was nothing to suggest anterior- pituitary insufficiency, since the patient lactated and cyclic menstrual periods were re-established following parturition. She was extremely exsanguinated on admission, as shown by the clinical picture of mild shock and severe anemia. Her response toe desiccated thyroid was most gratifying, since the uterine bleeding stopped after seven days of therapy. A checkup after three months off treatment revealed that she was clinically euthyroid. A remarkable change had taken place in the facies (Fig. 1). normal menses had returned. __________________ Author: JENNINGS C. LITZENBERG, M.D. Date Published: 01-Jan-1937 Publication: JAMA, 109:1871-1873, 1937 Title: THE ENDOCRINES IN RELATION TO STERILITY AND ABORTION Category: reproductive Keywords: reproductive, problem, LITZENBERG, ENDOCRINE, RELATION, STERILITY, ABORTION, fertile, pregnancy, develop, hormone, fetus, basal, metabolic, rate, menstrual, thyroid, women, normal Text: p1871 The endocrines govern the physiology of reproduction from beginning to end; spermatogenesis, ovogenesis, maturation of the ovum, ovulation, fertilization, preparation of the endometrium for nidation, implantation of the fertilized ovum, placentation, maintenance of pregnancy, development of the fetus, birth and lactation - all are dependent on hormones initiated and controlled by the anterior hypophysis. p1872 .....THE THYROID AND STERILITY Since 1922 I have studied the relation of the basal metabolic rate to sterility, abortions, and menstrual disturbances. In our first small series of sixty-nine consecutive sterile women, in whom no other evidence of myxedema was present, 50 per cent had a low basal rate; adding those who had conceived but aborted the figure was 56 per cent. Carefully supervised thyroid medication resulted in 33.3 per cent conception, 14 per cent of whom aborted. One woman conceived three times under thyroid medication, bringing the percentage of conceptions to 40. In another group of 114 women, 45 per cent of the married women were sterile and 40 per cent of the entire group had functional disturbances of menstruation. In a second series of 137 women, approximately the same figures were obtained, but in addition we found that 63 per cent had abnormal menses (our patients all came from a goiter area). Our third series (including the pervious reports) consists of 255 married women, 49.7 per cent of whom were sterile. Of 332 women, married and unmarried, 33.5 per cent had functional disturbances of menstruation. During the fifteen years of our experience to date (including cases not previously reported) there was a consistent rate of conceptions of 30 per cent in women with low basal rates. Haines and Mussey of the Mayo Clinic confirmed our thyroid treatment of functional menstrual disturbances, saying: " Because of a desire to determine the effectiveness of thyroid medication alone, in the treatment of certain menstrual disturbances, no patient received any other treatment. All were definitely improved; amenorrhea, 72 per cent; oligomenorrhea, 55 per cent; menorrhagia, 73 per cent, and general health, 75 per cent. " Also in this connection Haskins says: " Most gynecologists agree that thus far, of all the gland products, thyroid has proved to be the most useful for a variety of endocrine disturbances, including amenorrhea, oligomenorrhea, menorrhagia, sterility and abortion. " Marine, long ago (1917) when there was scarcely any usable knowledge of the endocrines, declared: " The relation of the thyroid to the sex organs in the female is the most frequent and classical illustration of the interrelation of the function of glands with internal secretions. " adds testimony by saying " The sole endocrine preparation that has proved itself of real value has been thyroid extract, which is of use in patients with lowered basal metabolism. " Novak declared that thyroid medication in sterility and abortion are more often efficacious than any other form of organotherapy. Desiccated thyroid was the first, and is still one of the few successful, substitutional hormone preparations. Perhaps when one gives desiccated thyroid one is doing to the ovaries what the pituitary has failed to do through stimulation of the thyroid gland by means of the thyrotropic hormone. I quote the concluding paragraph of an editorial in THE JOURNAL: These reflections [criticisms of the misuse of sex gland hormones] are not intended to inhibit chemical and biologic studies in accredited laboratories. Neither do they apply to the carefully controlled clinical application of accepted knowledge by competent observers; this is necessary. Rather are they intended (1) to emphasize that there is a great discrepancy between laboratory knowledge of the hormones and their clinical application, (2) to suggest that for the present only those clinicians with facilities for critical study be encouraged to administer the newer endocrine preparations to patients and that these clinicians be urged to publish their negative as well as their positive results, and (3) to suggest that a large group of physicians not represented in either of the groups mentioned cease their undiscriminating injection of unknown substances into unsuspecting patients. Physicians are perhaps cynical because of our limited knowledge of the endocrines and the complexity that faces it, but the tendency is to optimism when it contemplates the accomplishments of the recent past with their great promise for the future. _____________________ Author: RUTH C. FOSTER Date Published: 01-Jan-1939 Publication: ENDOCRINOLOGY 24:383,1939 Title: THYROID IN THE TREATMENT OF MENSTRUAL IRREGULARITIES Category: reproductive Keywords: reproductive, problem, FOSTER, THYROID, TREAT, MENSTRUAL, IRREGULAR, women, period, basal, metabolic, pelvis, metrorrhagia, amenorrhea, bleed, relief, continue, normal, desiccated Text: p383 DURING THE PAST few years we have been impressed by the efficacy of thyroid medication in the treatment of menstrual irregularities. Because our series of cases has shown results similar to those reported by clinicians working elsewhere, it has seemed worth while to summarize our data and present it in confirmation of material published previously. Fifty cases treated with thyroid have been observed for a period of from one to four years. These patients have been seen at least twice a month. Their ages have ranged from 16 to 34, although 41 of the series have been under 22 years of age. All have had complete physical examinations, pelvic studies, and repeated basal metabolic determinations. With a few exceptions, which will be discussed later, only those who showed no pathology in the pelvis have been treated with thyroid. .....Among this group of patients 25 complained of dysmenorrhea which was of sufficient severity to cause repeated absence from classes. Seventeen complained of scanty or delayed menstrual periods with intervals of as long as three months. Thirteen complained of too frequent periods or of inter-menstrual bleeding, while 7 had excessive flow together with the metrorrhagia. There were 5 cases of amenorrhea which was of 7 months to 4 years duration. Four of the patients had normal periods but there was a marked irritability with inability to concentrate for as long as a week prior to the period. p385 Of the 17 cases of oligomenorrhea, all reported definite relief as long as they continued taking thyroid. Several of this group tried going without therapy during the summer vacation but returned in the fall asking to resume treatment because their symptoms had recurred. All stated they felt much better when having their regular periods. .....The group of patients who complained of amenorrhea is small due to the fact that pathology was found to explain the cessation of periods in many of those who had this complaint. Those patients treated were given thyroid because their B.M.R. were low, and they or their parents wished them to receive a trial with thyroid before endometrial biopsies and further studies were made. p386 Those patients complaining of menorrhagia and metrorrhagia responded to thyroid therapy in a most satisfactory manner. The one failure was in a patient who had a large ovarian cyst removed because of prolonged menorrhagia. .....V.C., a university junior 18 years of age, consulted the Student Health Department because of a slight menstrual flow of six weeks duration, early fatigue, and a tendency towards a rapid gain in weight. She stated that her menstrual periods began when she was 13 and that they had always been irregular, occurring at intervals of three weeks to several months (9 months at one time). .....Treatment consisted of 1 to 2 gr. desiccated thyroid daily. The B.M.R. rose to -5, blood pressure to 108/78; the bleeding stopped and apparently normal periods occurred until the dose of thyroid was reduced, when there was a recurrence of the metrorrhagia. This patient has learned that she will have no symptoms I she takes thyroid in sufficient dosage to keep her B.M.R. -5 or above. This has been so consistent in her case that she can accurately predict her B.M.R. will be below these levels when the metrorrhagia recurs. p387 Four patients who complained of marked irritability prior to their periods are included in this series because their complaint was enough to interfere with their ordinary activities, and 3 did have relief with thyroid. Two noted partial relief, enough so that they did not want to stop thyroid medication. One had complete relief and one noted no difference. Thyroid was stopped several times but always with a recurrence of their symptoms. ..... DISCUSSION The explanation for the efficacy of thyroid medication in these cases can only be hypothesized. Experimental work in animals has shown that ablation of the thyroid is followed by an increase in size of the pituitary gland. Microscopic examination of these pituitaries shows hydropic degeneration, which explains the fact that after this procedure glands lose some of their potency. It may follow that in these patients there is an inadequate thyroid secretion resulting in a decrease in potency of the pituitary gland, which in turn causes inadequate gonad stimulation. One might go farther and state that the 4 patients who noted breast engorgement for the first time were having their first normal cycles with luteinization occurring. p388 Some of these problems may be solved by a study of endometrial biopsies before and after treatment. In a group of patients as young as these reported, most of whom are minors, it is difficult to obtain permission for biopsies from the parent, but as the public becomes educated to this procedure more parents should be willing to consent. It is our feeling that a B.M.R. should be obtained in all cases complaining of menstrual irregularities such as those reported above. Providing there is no pelvic pathology or physical condition to explain the symptoms, these patients should probably receive a trial with thyroid before further therapy is undertaken if their metabolic rates are below zero. It is understood that these patients will report periodically to their physicians and that the dose of thyroid will depend upon the individual response. In many cases there will be a complete relief of symptoms with small doses of thyroid although the metabolic rate has not reached what is considered the normal level. There is no way of predicting from the individual B.M.R. the degree of relief to be obtained. SUMMARY Fifty patients with ages ranging from 16 to 34 years were seen because of dysmenorrhea, oligomenorrhea, amenorrhea, metrorrhagia and menorrhagia. All were apparently healthy individuals with normal pelvic findings. These patients had B.M.R. ranging from -1 to -33 with an average of -15. All were treated with desiccated thyroid. Of 25 cases of dysmenorrhea 17 had complete relief, 5 partial, and 3 no relief. Of 4 patients with amenorrhea lasting from 8 months to 4 years only one had relief of her symptoms. Among 13 patients with metrorrhagia 12 had complete relief and of 7 with a menorrhagia 6 had complete relief. It is suggested that a B.M.R. should be determined in those individuals complaining of menstrual irregularities who have no demonstrable pathology to explain their symptoms. A therapeutic trial of thyroid is indicated if the B.M.R. is zero or below. ______________________ Author: BRODA O. BARNES M.D Date Published: 01-Jan-1949 Publication: MEDICINE January, 1949, Vol. 6, No. 1 pp. 33-34 Title: THE TREATMENT OF MENSTRUAL DISORDERS IN GENERAL PRACTISE Category: reproductive Keywords: reproductive, problem, BARNES, TREAT, MENSTRUAL, DISORDER, GENERAL, PRACTISE, thyroid, therapy, improve, patient, Basal, Temperature, relieve, bleed, women Text: The general practitioner can expect about 10 per cent of his patients to complain of menstrual difficulties. .....In 1939 and Thornton reported 50 cases of menstrual irregularities treated with thyroid therapy. Their results were far better than any published before or since. This present report of 143 cases is presented in confirmation of their work, and outlines an inexpensive plan of management which produces gratifying results. .....Control series for a group of cases of this kind are difficult. Each case serves as its own control for the period before therapy. Many of the patients relieved of their symptoms ceased medication and in a few months would have a return of their previous complaints. Thyroid therapy would again correct their menstrual difficulty. In view of the fact that the number of patients who were improved in the present series is almost identical, in proportion, with that of and Thornton in 1939, it seems reasonable to assume that the results are due to the treatment. SUMMARY One hundred forty-three cases of functional menstrual disorders have been studied. Dysmenorrhea, excessive bleeding and irregular menstrual cycles are included. The Basal Temperature usually is subnormal. Thyroid therapy relieves the symptoms in about 90 per cent of these cases. _______________________ Author: JOSEPH C. SCOTT, JR., M.D. Date Published: 01-Jan-1965 Publication: American Journal Obstetrics and Gynecology 90:161-165, 1965 Title: Menstrual patterns in myxedema Category: reproductive Keywords: reproductive, hypo, problem, pattern, myxedema, SCOTT, hypo, gland, menstruation, mild, test, menstrual, thyroid, hormone, menorrhagia, disease Text: 161 HYPOFUNCTION of the thyroid gland produces a broad spectrum of symptoms and signs, often including a change in the menstrual pattern. The various disorders of menstruation which may be associated with myxedema have been documented, but a difference exists in the reported frequency and types of abnormal menstrual pattern. Hypothyroidism has been implicated as the underlying cause of many irregularities of menstruation. .....Generally, it is believed that thyroid hormone is beneficial and its use is indicated only when there is evidence of thyroid hypofunction. A patient may be considered to be mildly hypothyroid by one clinician and euthyroid by another on the basis of only a single interview or test. No single test or procedure will define the status of the thyroid gland. Furthermore, any combination of methods may lead to erroneous interpretation or to inconsistent results. The clinician must have the faculty of correlating the clinical appearance of the patient with the laboratory findings. p 164 .....Comment Menorrhagia, that is, an increase in the amount and duration of menstrual flow, associated with myxedema may be mild, " occult, " or severe. Mild menorrhagia is a source of only minor concern and usually is corrected by better control of the myxedematous state. The term " occult menorrhagia " is warranted in cases in which there is excessive or prolonged menstruation which the patient considers to be normal. In these cases the onset of the menorrhagia has been so insidious that the patient is truly unaware of the change unless questioned closely (Case 2). Severe menorrhagia may require diagnostic curettage in addition to thyroid replacement therapy. Thyroid dysfunction should be considered in evaluation of each case of menstrual irregularity. Our studies reinforce the observations of other authors that menstrual disorders are not unusual in myxedema. A careful gynecologic examination should be performed for each patient suspected of having a thyroid disease. Any menstrual disorder should not be minimized and the possibility of genital malignant disease should be considered. Laboratory studies have greatly aided the clinicians in defining and evaluating thyroid disease states, but the " clinical appearance " of the patient should continue to be a prime factor in evaluation. Diagnostic measures, such as the quantitation of menstrual blood loss by tagging with radioactive chromium, are useful and informative in many patients, but not indispensable. Menorrhagia is the most frequent of the menstrual aberrations which are associated with myxedema. Hypomenorrhea and amenorrhea are much less common, and we have found oligomenorrhea to be rare. p 165 Summary The menstrual patterns of 50 premenopausal myxedematous women between 16 and 40 years of age were evaluated. Abnormal menstrual patterns occurred in 56 per cent of these patients. More than one form of menstrual irregularity was noted in two cases. Menorrhagia and metrorrhagia, alone or combined, constituted the abnormal patterns in 75 per cent of the patients. Amenorrhea occurs infrequently with myxedema. " Occult " menorrhagia should be considered in the evaluation of the patient with thyroid disease. _______________________ Author: Longcope Date Published: 30-Jun-1996 Publication: Werner and lngbar's The Thyroid, Seventh Edition, edited by E. Bravennan and D. Utiger. Lippincott-~ven Publishers, Philadelphia, @ 1996 Title: 71 The Male and Female Reproductive Systems in Hypothyroidism Category: reproductive Keywords: Longcope, reproduction, uterus, ovaries, hypo, thyroid, endometrial, muscle, animal, human, fertility, sexual, vagina, precocious, puberty, fetal, abort, testicular, sperm, libido Text: 849 HYPOTHYROIDISM IN THE FEMALE REPRODUCTIVE SYSTEM Hypothyroidism seems to affect the reproductive system in women more than in men. A review of the normal develop- ment and physiology of the female reproductive system has been given in chapter 47. Animal Studies In sheep, fetal hypothyroidism does not affect reproductive tract development but does result in prolonged gestation despite maternal euthyroidism.l However, in the rat, fetal hypothyroidism results in small ovaries deficient in lipid and cholesterol.2 Thyroidectomy of sexually immature rats results in delayed vaginal opening and sexual maturation; smaller ovaries and follicles than in controls3,4; and uteri and vaginas that are not well developed.5 When adult female rats are rendered hypothyroid their estrous cycles become irregular and their ovaries become atrophic.6 There is an enhanced response to HCG with the development of large cystic ovaries in hypothyroid rats.7 Hypothyroidism in hamsters and cows is associated with abnormal estrous cycles,s.9 and in hypothyroid hens there is a decrease in egg production.9 In the mature female rat, hypothyroidism apparently does not result in sterility but does interfere with gestation, especially in the fIrst half of pregnancy,lO with resorption of the embryo and subsequent reduction in litter size and an increase in stillbirths.ll In hypothyroid sheep, the uterus shows endometrial hyperplasia and smooth muscle hypertrophy, perhaps related to the prolonged estrous noted in hypothyroid ewes.12 Ruh and coworkers 13 reported increased estradiol binding in uteri of hypothyroid rats, but Kirkland and coworkers 14 found a decrease in the uterine response to estrogen in hypothyroid rats. Hypothyroidism inhibits the photoperiod responses and seasonal breeding patterns in sheep and birds.15,16 Human Studies and Clinical Aspects The reproductive tract appears to develop normally in cretins; thus, hypothyroidism during fetal life does not appear to affect the normal .development of the reproductive tract. Hypothyroidism in prepubertal years generally leads to short stature and may lead to a delay in sexual maturity.4 However, an interesting syndrome described by Kendlell and Van Wyk and Grumbach 18 occurs not infrequently: it is characterized by precocious menstruation, galactorrhea, and sella enlargement in girls with juvenile hypothyroidism. The cause is thought to be an overlap in the pituitary production of TSH and gonadotropins, with the latter causing early ovarian secretion of estrogens and subsequent endometrial stimulation with vaginal bleeding. Prolactin levels are elevated, leading to galactorrhea. However, there is no pubertal increase in the adrenal production of androgen precursors, so that axillary and pubic hair are usually not apparent.I8 Therapy with thyroxine in proper dosage results in prompt alleviation of the symptomatology. In adult women, hypothyroidism results in changes in cycle length and amount of bleeding I9-21 and has been reported 850 in association with the ovarian hyperstimulation syndrome.22 Menorrhagia is a frequent complaint and is probably due to estrogen breakthrough bleeding secondary to anovulation, which is frequent in severe hypothyroidism. 19 The anovulation is reflected in the frequent finding of a proliferative endometrium on endometrial biopsy.23 TRa-l and TRBB-1 receptors have been found in human granulosa cells and both triiodothyronine and thyroxine have been found in follicular fluid.24 Earlier work in- dicated that thyroxine enhanced the action of gonadotropins on luteinization and progestin secretion by cultured granulosa cells,25 and it has recently been noted that in a group of infertile women, those with elevated TSH levels had a higher incidence of out-of-phase biopsies than women with normal TSH.26 Ovulation and conception can occur in mild hypothyroidism, but in the past those pregnancies that did occur were often associated with abortions in the first trimester, stillbirths, or prematurity, 19,27 Recent studies indicate these events may be less common but that gestational hypertension occurs often in pregnant women with untreated hypothyroidism.28 Pregnancy occurring in women with myxedema has been reported to be uncommon,27 but this is somewhat hard to document and may be the result of anovulation. The use of L-thyroxine is not helpful in treating euthyroid patients for infertility, menstrual irregularity, or the premenstrual syndrome.29,30 In evaluating the thyroid status of the pregnant woman, the level of TSH is probably the best indicator of changes in thyroid function. Because radioiodine will readily cross the placenta and can cause fetal hypothyroidism, tests involving ra- dioiodine administration to the mother are contraindicated in pregnancy.19 When hypothyroidism is diagnosed during pregnancy, L-thyroxine therapy should be instituted promptly to increase the chances for a normal pregnancy. Although it has been thought that little L-thyroxine would cross the placenta,19 it appears that L-thyroxine will cross the placenta in modest amounts,31 at least early in pregnancy. Women who have required thyroid hormone therapy prior to pregnancy should continue with such therapy throughout the pregnancy. How- ever, recent evidence indicates that the hormone dose needs to be increased during pregnancy, even though adequate replacement had been given before conception.31 It is advisable to monitor the serum TSH concentration at least once during each trimester to ensure that an adequate dose is received. Thyroid disease during and after pregnancy is discussed in detail in chapter 89. Some myxedematous women will present with amenorrhea and galactorrhea and elevated serum prolactin concentrations.19 Thus, thyroid evaluation should be an essential part of the work-up in any person with galactorrhea. If hypothyroidism is the cause, the amenorrhea and galactorrhea and elevated serum prolactin will disappear promptly with thyroxine therapy.32 There is an increased incidence of Hashimoto's thyroiditis in individuals with 's syndrome,33 and, although a chromosomal linkage between autoimmtme disease and the X- chromosome has been suggested, this has not been confirmed.34 Inherited abnormalities in serum thyroxine-binding globulin (TBG) are X-linked, and patients with 's syndrome may ,have low serum TBG values.35 Women with hypothyroidism have decreased metabolic clearance rates of androstenedione and estrone and increased peripheral aromatization.36 The ratio of 5a/5B metabolites of androgens is decreased in hypothyroid women, and there is an increase in the excretion of estriol and a decrease in the excretion of 2-oxygenated estrogens.37 In summary, hypothyroidism in girls can cause alterations in the pubertal process; this is usually a delay, but occasionally it can result in pseudoprecocious puberty. In mature women, hypothyroidism usually is associated with abnormal menstrual cycles, especially anovulatory cycles, and an increase in fetal wastage. HYPOTHYROIDISM IN THE MALE EPRODUCTIVE SYSTEM The normal development and physiology of the male reproductive system has been described in chapter 47. Although less common in men than in women, hypothyroidism, induced or spontaneous, affects the male reproductive tract in a number of ways depending, in part, on the age of onset. Animal Studies The fetal thyroid starts functioning about the same time as the gonads.38 Although thyroid hormones play role in sex differentiation and gonadal maturation in fish and amphibians,39 they do not appear to be necessary for the normal development of the reproductive tract in mammals. 1 However, hypothyroidism, induced or occurring soon after birth, is associated with a marked delay in sexual maturation and development.40 When rats are made hypothyroid with propylthiouracil administered from birth to 24 to 26 days of age, testicular size is decreased, Sertoli cell differentiation is retarded, and the time of Sertoli cell proliferation is prolonged.4].42 As these rats become older and euthyroid, then the testis size, Sertoli cell number, and sperm production are all increased.41, Leydig cell numbers are increased but testosterone secretion per cell is decreased, although total testosterone secretion remains the same as controls.43 FSH and LH levels tend to remain low throughout treatment and recovery periods, whereas inhibin levels are elevated.41 However, if hypothyroidism persists untreated, there is an arrest of sexual maturity with absent libido and ejaculate.44 The interstitial cells of the testis are reduced in number and the arrested growth of the accessory male sex organs indicates a decrease in the production of testosterone.44 The longer the hypothyroidism persists, the greater the degree of damage to the testes,44 although genetically induced hypothyroidism in male mice is associated with normal fertility .45 In the adult ram, hypothyroidism is associated widl a decrease in testosterone concentration but normal spermatogenesis.46 In the mature male rat, the induction of hypothyroidism has little effect on the pathology of the testes, sperlllatogenesis, or serum testos- terone concentrations.47 Thus, it would appear that hypothyroidism can affect the immature, but not the mature, testis. Human Studies and Clinical Aspects The development of hypothyroidism in the male fetus does not appear to affect the reproductive system. Cretins are usually born with a normally developed reproductive tract. The presence of hypothyroidism in the prepubescent years usually results in a delay of sexual maturation and of the whole pre-pubertal process, which can be overcome by the administration of adequate doses of thyroxine. However, in some instances, hypothyroidism can result in precocious pseudopuberty marked by the early development of external genitalia, but without the appearance of axillary and pubic hair. 48 This syndrome probably results from an increased secretion of gonadotropins along with TSH from the enlarged pituitary.48 In men, hypothyroidism has been suggested as a cause of infertility,49 but there is considerable disagreement with this suggestion. 50 If an infertile man is found to be hypothyroid, one should suspect secondary hypothyroidism and pituitary disease rather than primary myxedema, and there is no reason to treat infertile euthyroid men with thyroid hormone.50 In hypothyroid men, testicular size and potency may be normal and, despite early reports of defective spermatogenesis in hypothyroidism, 51 semen analysis is usually normal.52 Wortsman and colleagues reported that myxedema was often associated with infertility and impotence, but in this report the impotence did not improve when the men became euthyroid.49 In addition, there was a decrease in serum testosterone and free testosterone and, in the men who were not over-weight, an increase in sex hormone-binding globulin. It should be noted that sex hormone-binding globulin levels have also been reported as both decreased53 and normal 54 in hypothyroid men. Many men with hypothyroidism do note a decrease in libido, but this is probably a nonspecific disease-related complaint, which disappears when the euthyroid state is achieved with thyroid replacement therapy. Variations in testis size and histology have been noted in autopsy material,55,56 and De La BaIze and coworkers 51 noted Leydig cell hyperplasia and tubular hyalinization. There is a marked decrease in the 5a/5B ratio of the metabolites of androstenedione and testosterone, which is the reverse of that seen in hyperthyroidism 57 In summary, although hypothyroidism in boys frequently interferes with the normal pubertal process, the development of hypothyroidism in men has a less clear-cut effect on the reproductive system. References - not thoroughly checked 1. Hopkins PS, Thorburn GD. The effects of foetal thyroidectomy on the devel2. Leathem JH. Extragonadal factors in reproduction. In: Lloyd CW, ed. Recent progress in the endocrinology of reproduction. New York: Academic Press, 1959:179 3. Leathem]H. Role of the thyroid. In: Balin H, Glasser S, eds. Re- productive biology. Amsterdam: Excerpta Medica, 1972:23 4. Hayles AB, Cloutire MD. Clinical hypothyroidism in the young— a second look. Symp Endocr Disorders 1972:56:871 5. Scow RO, Simpson ME. Thyroidectomy in the newborn rat. Anat Rec 1945;91:209 6. Ortega E, E, Ruiz E. Activity of the hypothalamo- pituitary ovarian axis in hypothyroid rats with or without tri- iodothyronine replacement. Life Sci 1990;46:391 7. Takacs-Jarrett M, Broot BC. Steroid secretion by follicles and cysts from the hypothyroid, hCG-treated rat. Sac Experimental BioI Med 1994;207:62 8. Vriend J, Bertalanffy FD, Ralcewicz TA. The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in fe- male Syrian hamsters. Bioi Reprod 1987;36:719 9. Maqsood M. Thyroid functions in relation to reproduction of mammals and birds. Bioi Rev 1952;27:281 10. Bonet B, Herrera E. Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat. Endocrinology 1991;129:210 11. Rao PM, PandaJN. Uterine enzyme changes in thyroidectomized rats at parturition. J Reprod FertiI1981;61:109 12. Nesbitt REL, Abdul-Karim RW, Prior JT, TF, Rourke JE. Study of the effect of experimentally induced endocrine insults upon pregnant and nonpregnant ewes. m. ACfH and propyl- thiouracil administration and the production of polycystic ovaries. Fertil Steril1967;18:739 13. Ruh MF, Ruh TS, Klitgaard HM. Uptake and retention of estro- gens by uteri from rats in various thyroid states. Proc Soc Bioi Med 1970;134:558 14. Kirkland JL, Gardner RM, Mukku VR, Akhtar M, Stancel GM. Hormonal control of uterine growth: The effect of hypothy- roidism on estrogen-stimulated cell division. Endocrinology 1981;108:2346 15. Moenter SM, Woodfill CJI, Karsch FJ. Role of the thyroid gland in seasonal reproduction: Thyroidectomy blocks seasonal suppres- sion of reproductive neuroendocrine activity in ewes. En- docrinology 1991;128:1337 16. Dawson A. Thyroidectomy progressively renders the reproduc- tive system of starlings (Sturnus vulgaris) unresponsive to changes in daylengtll. J EndocrinoI1993;139:51 17. Kendle F. Case of precocious puberty in a female cretin. Br Med J 1905;1:246 18. Van Wyk J, Grumbach MM. Syndrome of precocious menstrua- tion and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap pituitary feedback. J Pediatr 1960;57:416 19. R, Reid RL. Thyroid disease and reproductive dysfunc- tion: a review. Obstet GynecoI1987;70:789 20. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. AmJ Obstet GynecoI1989;160:673 21. Higham]M, Shaw RW. TIle effect of thyroxine replacement on menstrual blood loss in a hypothyroid patient. Br J Obstet Gy- naecol 1992;99:695 22. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimu- lation syndrome associated with hypothyroidism. Am J Obstet GynecoI1989;160:1220 23. Goldsmith RE, Sturgis SH, Lerman J,. Stanbury JB. The menstrual pattern in thyroid disease. J Clin Endocrinol Metab 1952;12:846 24. Wakim AN, Polizotto SL, Buffo ML, Marrert;> MA, Burholt DR. Thyroid hormones in human follicular fluid and thyroid hor- mone receptors in human granulosa cells. Fertil Steril 1993;59:1187 25. Channing CP, Tsai V, Sachs D. Role of insulin, thyroxine and cor- tisol in luteinization of porcine granulosa cells grown in chemi- cally defined media. Bioi Reprod 1976;15:235 26. Gerhard I, Becker T, Eggert-Kruse W, Klinga K, Runnebaum B. Thyroid and ovarian function in infertile women. Hum Reprod 1991;6:338 27. LE, Leveno KJ, Cunningham FG. Hypothyroidism compli- cating pregnancy. Obstet Gynecol1988;72:108 28. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JR. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993;81:349 29. Nikolaj TF, Mulligan GM, Gribble RK, Harkins PG, Meier PR, RC. Thyroid function and treatment in premenstrual syn- drome.J Clin Endocrinol Metab 1990;70:1108 30. Roti E, Minelli R, Gardini E, Braverman LE. The use and misuse of thyroid hormone. Endocr Rev 1993;14:401 852 31. Burrow GN, Fisher DA, Larsen PRo Maternal and fetal thyroid function. N EnglJ Med 1994;331:1072 32. CRW, Forsyth lA, Besser GM. Amenorrhea, galactorrhea and primary hypothyroidism with high circulating levels of pro- lactin. Br MedJ 1971;3:462 33. Van Campenhout J, Van J, Antaki A, Rasio E. Diabetes mellitus and thyroid autoimmunity in gonadal dysgenesis. Fertil Steril 1973;24:1 34. Vallotton ME, Foibes AP. Autoimmunity in gonadal dysgenesis and Klinefelter's syndrome. Lancet 1967;1:648 35. Refetoff S, Selenkow HA. Familial thyroxine-binding globulin deficiency in a patient with 's syndrome (XO). N Engl J Med 1968;278:1081 36. Longcope C, Abend S, Braverman LE, Emerson CR. Androstene- dione and estrone dynamics in hypothyroid women. J Clin En- docrinol Metab 1990;70:903 37. Gallagher TF, Fukushima DK, Noguchi S, et al. Recent studies in steroid hormone metabolism in man. Recent prog Horm Res 1966;22:283 38. Saenger P. Abnormal sex differentiation. J Pediatr 1984;104:1 39. Lynn WG. The thyroid gland and reproduction in cold blooded vertebrates. Proceedings of the Fifth Mid-West Conference Thy- roid 1969;17 40. Palmero S, de Marchis M, Gallo G, Fugassa E. Thyroid hormone affects the development of Sertoli cell function in the rat. J En- docrinoI1989;123:105 41. Kirby JD, Jetton AE, Cooke PS, et al. Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced in- crease in adult testicular size and sperm production in the rat. Endocrinology 1992;131:559 42. Van Haaster LH, de Jong PH, Docter R, De Rooij DG. The effect of hypothyroidism on Sertoli cell proliferation and differentia- tion and hormone levels during testicular development in the rat. Endocrinology 1992;131:1574 43. Hardy MP, Kirby]D, Hess RA, Cooke PS. Leydig cells mcrease their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 1993;132:2417 44. Gomes WR. Metabolic and regulatory hormones influencing testis function. In: AD, Gomes WR, Vandemark NL, eds. The testis. Vol III. Influencing factors. New York: Academic Press, 1970:67 45. Chubb C, Henry L. The fertility of hypothyroid male mice. J Re- prod Fertil1988;83:819 46. dIandrasekhar Y, Holland MK, D'Occhio Mj, Setchell BP. Sper- matogenesis, seminal characteristics and reproductive homlone levels in mature rams with induced hYPQthyroidism and hyper- thyroidism. J EndocrinoI1985;105:39 47. Weiss SR, Burns JM. The effect of acute treatment with two goitrogens on plasma thyroid hormones, testosterone and testic- ular morphology in adult male rats. Comp Biochem Physiol (A) 1988;90A:449 48. Castro-Magana M, Angulo M, Canas A, Sharp A, Fuentes B. Hy- pothalamic-pituitary gonadal axis in boys with primary hypothy- roidism and macroorchidism. J Pediatr 1988;112:397 49. Wortsman J, Rosner W, Dufau ML. Abnormal testicular func- tion in men with primary hypothyroidism. Am J Med 1987; 82:207 50. Steinberger E. The thyroid gland in male infertility. In: C-R, Mastroianni LJr, Amelar R, Dubin 1, eds. Current therapy of infertility 1982-1983. St Louis: CV Mosby, 1982:15 51. De La BaIze FA, Arrilloga F, Mancini RE. Male hypogonadism in hypothyroidism: a study of six cases. J Clin Endocrinol Metab 1962;22:212 52. Griboff S. Semen analysis in myxedema. Fertil Sterill962;13:436 53. Cavaliere H, Abelin N, Medeiros-Neto G. Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. J AndroI1988;9:215 54. De Nayer P, Lambot MP, Desmons MC, Rennotte B, Malvaux P, Beckers C. Sex homlone-binding protein in hyperthyroxinemic patients. A discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab 1986;62:1309 55. s RC, son SD. Pathologic changes in adult myxedema: survey of 10 necropsies. j Clin Endocrinol Metab 1957;17:1354 56. Marine D. Changes in the interstitial cells of the testis in Gull's disease. Arch PathoI1939;28:65 ____________________________ Author: Sheldon S. StofIer. MD Date Published: 01-Jan-1982 Publication: POSTGRADUATE MEDICINE. VOL 72/NO 2/AUGUST 1982 Title: Menstrual disorders and mild thyroid insufficiency Intriguing cases suggesting an association Category: reproductive Keywords: reproductive, problem, StofIer, Menstrual, disorder, mild, thyroid, insufficiency, case, suggest, association, pathology, patient, treat, levothyroxine, hypo, hyper, TSH, TRH Text: Should patients with menstrual dysfunction but without obvious uterine pathology be considered for thyrotoxin-releasing hormone (TRH) testing? In several cases described here. an apparent relationship between menstrual disturbance and minimal thyroid insufficiency was documented by the patients' dramatic response to treatment with levothyroxine. The association of overt hypothyroidism or hyperthyroidism with menstrual disturbance and infertility is well known.15 However, menstrual disturbance may also be related to minimal thyroid insufficiency, as the following cases suggest. The past ten years have brought enonnous advances in the ability to diagnose mild thyroid dysfunction. The introduction of serum thyroxine and serum thyroid -stimulating hormone (TSH) radioimmunoassays has increased the sensitivity and specificity of thyroid function testing. The serum TSH assay has been shown to be a sensitive indicator of diminished thyroid functional reserve. since TSH levels become elevated before circulating serum thyroxine levels fall below the normal range 6, Thyrotropin-releasing hormone (TRH) is a simple tripeptide nonnally found in the hypothalamus. Its availability in synthetic fonn, protirelin (Thypinone, Relefact TRH), has provided a convenient provocative test of pituitary TSH reserve and has further extended the sensitivity of thyroid testing. In fact, this TRH test is so sensitive that results may be markedly abnormal in patients with no signs or symptoms of thyroid disease.6 Patients with minimal impairment of thyroid functional reserve who have normal serum thyroxine and normal baseline serum TSH levels may have an augmented TSH response to TRH administration.6 76 76 Table 1. Results of thyroid function studies in four patients with menstrual disturbance treated by levothyroxine therapy Case Time of testing Thyroid function study FTI* Baseline TRH:+ TSHt 1 Initial study 2.2 6.0 58.0 After26mo of treatment 2.9 3.0 11.7 2 Initial study 1.9 7.1 57.3 After 6 mo of treatment 3.5 1.6 1.8 3 Initial study 1.7 Two years later 2.1 7.2 52.9 After 3 mo of treatment 2.0 1.2 After 21 mo of treatment 2.6 2.8 14.3 4 Initial study 1.8 9.3 >80 After2 mo of treatment 3.8 3.0 6.1 After 14 mo of treatment 1.7 16.4 >80 After 2 mo of increased 3.6 2.5 2.5 dosage * Free thyroxine index (total T4 x T3 resin uptake). normal range 1.4-4.0 +Thyroid-stimulating hormone by radioimmunoassay, normal <8.0 uU/mc tThyrotropin-releasing hormone test (serum TSH rise 20 min after administration of 100 ug TRH), normal range 2-20 uUI ml 80 ...... Discussion In the past, when thyroid test-ng was nonspecific, inaccurate, and insensitive, desiccated thyroid tablets were often given empirically to women with menstrual dysfunction and/ or infertility. Some of these patients may have improved, reinforcing this unscientific and currently unjustifiable approach. At least a portion of these women may have actually had subclinical, and at that time undetectable, thyroid insufficiency. ...... Recently, I encountered a 32 year-old patient with evidence of very mild thyroid insufficiency who had undergone hysterectomy four years before because of troublesome hypermenonorrhea The patient had a diffuse goiter 11/2 times normal size, and antimicrbsomal antibodies were positive at 1:6,400 dilution. Serum FTI was 1.5, baseline serum TSH was 6.3 µU/m1, and serum TSH 20 minutes after TRH administration was 60.7 µU/m1. The pathology report revealed a normal-sized uterus With a predominantly proliferative endometrium and a normal myometrium. Although mild thyroid dysfunction cannot be proven responsible for this patient's abnormal menstrual bleeding, one wonders if TRH testing could have avoided the need for hysterectomy in this case and perhaps in similar cases. ...... 82 ...... Recommendations Based on my experience, I would recommend that patients \vith long- standing menstrual dysfunction without obvious uterine pathology be considered for TRH testing. Such testing would be especially fruitful in patients with goiter, high-nrmal baseline serum TSH value, or family history of thyroid disease. I would certainly not encourage empirical use of thyroid hormone in such a patient population without appropriate testing. Because mild thyroid insufficiency is so easily treated, TRH testing and atrial of thyroid hormone therapy, if .indicated, should be considered in difficult cases of menstrual dysfunction prior to hysterectomy. Summary Three cases of menstrual disturbance possibly related to minimal thyroid insufficiency are reported. In all cases, tltyrotropin- releasing hormone testing was sensitive enough to detect evidence of tltyroid abnormality .Without exception, treatment with levothyroxine caused a dramatic end to menstrual difficulty. In two of these cases, levotltyroxine tlterapy was discontinued and the menstrual abnormality returned. Resumption of levotltyroxine treatment led to prompt retum of normal menstruation. A fourth case is presented which suggests tltat placebo effect alone is probably not responsible for the observed menstrual improvement. It is possible that minimal thyroid insufficiency can lead to marked menstrual disturbance. References I. Goldsmith RE. Sturgis SH. Lennan J. et a!. The menstrual pattern in thyroid disease J Clin Endocrinol Metab 1952 12: 846-55 2. Distiller LA. Sage1 J. Morley JE. et a!. Assess ment of pituitary gonadotropin reserve using luteinizing hormone releasing hormone (LRH) in states of altered thyroid function J Clin Endocrinol Metab 1975:40, 512-15 3. Keye WR. Yuen BH. KnopfRF. et a!. Amenorrhea yperprolactinemia, and pituitary enlargement secondary to primary hypothyroidism Obstet Gyneco 1976:48,697-702 4. Van Wyk JJ. Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism an example of hormonal overlap in pituitary feedback J Pediatr 1960:57,416-35 5. Tolis G. Hoyte K. McKenzie JM. et al. Clinical.biochemical and rndlologic reversibility of hyperprolactinemic galactorrhea.amenorrhea and abnorma sella by thyroxine in a patient with primary hypothyraidisrn Am J Obstet Gynecol 1978:131, 850-2 6. Ingbar SH. Woeber KA. The thyroid gland In: Willams R. ed, Textbook of endocrinology 6th ed Philadelphia WB Saunders, 1981: 117- 247 7. Buchanan GC. Tredway DR. Pittard JC. et a!.Gonadotropin secretion and hypothyroidism Obstet Gynecol 1977: 50,392-6 S. CoUu R. Abnormal pi tui tary hormone response to thyrotropin- reieasing hormone an index. of central nerve system dysfunctlon In Tolis G, Labrle, F JB, et al. eds Cllnical neuroendocrinology a pathophysiological approach New York Raven Press 1979: 129-37 9. Snyder PJ. s LS. Utige RD et al. Thyroid hormone inhibitlon of the prolactin response to thyrotropin-releasing hormone J Clin Invest 1973: 52,2324-9 10. Tolls G. Prolactin physiology and pathology In: Krieger DT JC eds Neuroendocrinology Sunderland. MA Sinauer Assoc, 1980: 34,322-8 11. Powers JM. Block MB. Primary hypothyroidlsm with reversible hypeprolactinemia and pituitary enlargement Ariz Med 1989:37, 256-8 12. Stoffer SS. McKee1 DW Jr. Randall RV, et a!. Pituilary prolactin cell hypetplasia with autonomous prolactin secretlon and primary hypothytoidism Fertil Steril 1981: 36,682-5 __________________ Author: Luoto R Date Published: 27-Jun-1997 Publication: Int J Epidemiol 1997 Jun;26(3):476-83 Title: Hysterectomy and subsequent risk of cancer. Category: reproductive Keywords: Luoto, Hysterectomy, subsequent, risk, cancer, Elevate, papillary, thyroid, follow, reproductive, endocrinological, cause, high, breast, peri, retrospective, study, menopause, total, pre Text: BACKGROUND: The objective of this retrospective cohort study was to assess the effect of hysterectomy on subsequent risk of cancer among 25,382 hysterectomized and a similar number of non- hysterectomized control women, registered in 1963-1976 in the Mass Screening Registry (MSR). METHODS: Cancer cases were obtained from the Finnish Cancer Registry (FCR) and standardized incidence ratio (SIR); the expected number of cases based on cancer incidence rates of the Finnish female population in 1967-1993, was used. Relative risk (RR) was calculated as SIR among the hysterectomized relative to non-hysterectomized women, adjusted for follow-up, education and parity. RESULTS: The RR estimates of non-genital cancers among women with any hysterectomy were approximately 5% higher than in the non- hysterectomized cohort. Relative risks of rectal cancer (RR = 1.4, 95% confidence interval [CI]: 1.0-1.8) and thyroid cancer (RR = 2.1, 95% CI; 1.5-3.1) were significant and largest among women who had undergone total hysterectomy pre- or perimenopausally. Relative risk estimates of breast cancer were close to unity. CONCLUSIONS: Hysterectomy is not associated with any substantial protective or promoting effect on cancers in general. Elevated risk of papillary thyroid cancer following hysterectomy is biologically plausible, as there are reproductive and endocrinological causes of thyroid cancer. National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland. PMID: 9222770 [PubMed - indexed for MEDLINE] _____________________ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 19, 2005 Report Share Posted March 19, 2005 I don't believe coffee is a problem. Have you ever noticed that people are willing to give up coffee for their fibroids, but won't give up chocolate even though it has some bad things in it that are just as bad as coffee? I started to think, after being on fibroid newsgroups for three years, that people think that if it's good and give pleasure, then somehow it's bad for fibroids. Sort of like fibroids are caused by sin and if we sacrifice those things we love to be healed. The other notion people seemed to have a lot is that fibroids are the cause stuck energy and emotional issues that are not worked out. This one is one of those classic " blame the victim " notions. You are the cause of your own illness and if you can somehow fix your sick mind or maybe " find God " or do some peace work, you will be cured and your punishment removed. I suppose coffee does increase adrenal output and this might raise cortisol and high cortisol tends to increase estrogen. But, I don't know how you could say coffee is any worse than a serving of beans or nuts or drinking out of plastic or spraying weeds in your yard with pesticides or eating meat of animals given growth hormone and on and on. Where do you draw the line? The biggest cause of fibroids in my book is low thyroid, combined with genetics, and stress, which plays into the thyroid problems. A big study was done in Italy on eating habits and fibroids. The only thing they could find that correlated was the amount of red meat eaten. The correlation was very weak at best and did not really prove it unequivically. Tish ______________________ Here are some things I have collected on this topic. ______________________ But menstrual irregulaities are not the only hrmful affect low thryoid has on the uterus. A lack of thyroid greatly enhances the growth of uterine fibroids as well. If a woman is on sufficient amounts of thyroid the further growth of uterine fibroids usually will be blocked and frequently they will start shrinking. Besides uncontrolled bleeding, the major reason that women have hysterectomies is symptomatic uterine fibroids which can cause discomfort and contribute to excessive bleeding. Hypothyroidism also increases the incidence of uterine cancer which is the reason behind most the remaining hysterectomies. So thyroid has an almost magical impact on many of the woes associated with womanhood; it takes them away. (Page 117) And as mentioned elsewhere, there is a close relationship between the binding sites of thyroid and the binding sites of estrogen, so the function of thyroid and estrogen are intertwined in subtle ways. (Page 116) " Thyroid, Guardian of Health " by Philip G. Young, MD, Trafford Publishing, , BC., Canada, 2002 __________________________ Fibroid tumors have been rare in hypothyroid women who have been maintained on adequate thyroid therapy. It is possible to produce fibroids in experimental animals by injection of estrogens, and there is evidence of excess of estrogens in hypothyroid women. In hypothyroidism, there is increased activity of the pituitary gland aimed at trying to stimulate the thyroid to produce more hormone secretions, and the increased pituitary activity may spill over to affect ovaries and increase their estrogen output. (Page 133) " Hypothyroidism: The Unsuspected Illness " by Broda O. , M.D. and Lawrence Galton, Harper & Row, Publishers, New York, 1976 ________________ [Diagnosis of thyroid function in uterine myomatosis] [schilddrusenfunktionsdiagnostik bei Myomatosis uteri.] Zentralbl Gynakol 1989;111(1):47-52 (ISSN: 0044-4197) Lange R; Meinen K Gynakologisch-Geburtshilflichen Abteilung, St. Lukas Klinik Solingen. A correlation between thyroid disease and uterine myoma has been discussed till the fourth decade of this century. Since then, this possible connection was given no further notice. We examined 79 women needing a hysterectomy for various reasons regarding myometrial histology, thyroid function and thyroid antibodies. The patient group bearing myomas showed significantly more frequent (23%) pathological TRH/TSH stimulation tests results than the control group (3.7%, p = 0.0543). 10 of 22 patients with myomas had microsomal and/or thyroglobin antibodies, compared with none in the control group (n = 17, p = 0.0019). Therefore regarding these results a connection between thyroid disease and uterine myoma should undergo a more detailed examination. ______________________________ Part B - Oestrogen, Progesterone & Testosterone The hormones that keep us male and female are crucially affected by thyroid and adrenal function; and in turn can effect the proper functioning of the thyroid itself. So let us see where they fit in. Since my approach to metabolic problems is holistic, we have to ask if thyroid and adrenal insufficiency may be altered or worsened by deficiencies elsewhere. The answer is of course, yes. Since a state of lowered metabolism means that nothing really works as it was designed to, it follows that other hormone producing glands may not do their job properly either. It is a bit like an extraordinarily complex piece of electrical machinery, designed for 240 volts, running on 210 volts. It runs, but the lights look a bit dim and flicker a bit. Bringing up the voltage - gently - will get everything working again. So far as other components of the endocrine system go, we must be prepared for partial recovery only, and supplementation may well be indicated elsewhere as well. We are talking mostly about sex hormones here, and the effects of the menopause on both sexes. We have learnt already how important the adrenal corticosteroids are in the maintenance of the body's normal health; the male and female sex hormones, which are of course also steroids, are just as extraordinarily important in their own right. (It may have perhaps surprised you to realize that the whole body, most especially many of its hormones, is based on the steroid molecule. The use of the word " steroid " has been denigrated in the popular mind as being potentially, if not actually, dangerous, and this is a complete distortion. The contraceptive pill, for which millions of prescriptions are written weekly, is based on two steroids and few doctors and few patients are especially concerned that they do in fact belong to the great family of steroids). We will start with the female menopause, which will be hastened or worsened by a low thyroid/adrenal state. Literally, the menopause means " the last period " . For some women this is an abrupt thing, there one month and gone the next. Very often the process is rather more protracted than this; the periods start lengthening and sputter about; they may become heavy with pain and floods, or become very light and irregular. And menstrual problems, with heavy irregular periods, are certainly associated with low thyroid. So we need to have a look at the whole business, so that we can decide to intervene if necessary while treating the metabolic problems. Women actually produce three different sex hormones, oestrogen (which has three different forms: oestradiol, oestrone and oestriol), progesterone and testosterone. You thought testosterone was a male hormone, didn't you. Well, it is; but women produce it too - though less than men of course. (The reverse is also the case.) In general oestradiol, the main oestrogen, comes from the ovaries, the other two from the adrenals, directly or indirectly, and more after the menopause. The way it all works is this. As the menarche (the start of periods) approaches, the ovaries start to produce oestrogen and under the influence of a pituitary hormone, the Follicle Stimulating Hormone (FSH), an ovarian follicle (of which there are many hundreds containing egg cells waiting their time) matures an ovum which surfaces about mid cycle and is released. It finds its way into one of the fallopian tubes (right or left, depending on which ovary produced the ovum) where it may or may not be fertilized. The place from where it was released on the ovary undergoes a change to produce the Corpus Luteum or " Yellow Body " . This structure begins to produce under the influence of Luteinizing Hormone (LH) from the pituitary, another hormone, progesterone. This prepares the lining of the womb for implantation if the ovum is fertilized. Oestrogen and progesterone are produced together for the second half of the cycle; and then the supply is cut off abruptly which starts off the menstrual period. Hypothyroidism can affect this process in several ways. To start with, a low thyroid state affects the onset of the first period, oddly enough in two opposing ways. The first period may come unusually early at 8, 9 or 10 years old; or, it may come unusually late, 15, 16 or 17 years old. Periods starting abnormally like this should raise a suspicion about the thyroid at once. The periods may be abnormal in other ways. They may be exceedingly painful with collapse and prostration of the unfortunate girl; they may be very heavy or very light or come at irregular times. There may be premenstrual tension to make life miserable. These problems may occur at any time of life, but may sort themselves out a bit after having children. Then in the later thirties and early forties it all goes wrong and flooding and terrible PMT may ruin things so badly that relationships suffer. The gynecologist may not think of thyroid dysfunction as a cause and the ladies then become the target of various synthetic hormone combinations, which may or may not bring relief. It is at this point, of course, that hysterectomy becomes the treatment choice, and worn out with it all, the unhappy sufferer consents to surgery. Relief from the terrible periods may well justify the hysterectomy for the patient; but it may have missed the point altogether. As I said earlier, hysterectomy is very likely to affect thyroid activity. There seems to be a chemical dialogue between the womb and the thyroid; and interference - including sterilization, termination, or even a D&C, seems to damage thyroid function for many. The weight gain, which nearly always occurs, is not due to comfort eating while grieving for one's lost fertility, but because thyroid activity may be further damaged. This, and the other symptoms of a running down of thyroid activity, is a heavy price to pay for an operation for which one out of every three, at least, wasn't necessary and could have been avoided if thyroid status had been properly assessed and treated. The other worry which besets women at this time of their lives is premenstrual tension (PMT) or as the Americans call it (PMS) premenstrual syndrome. Some doctors won't have that this occurs at all. I remember reading an authoritative article by a lady doctor who discounted it completely; one just wonders what planet she came from. Not only is it a very real problem; if anything it is getting worse. Although a number of causes have been cited, it seems clear that it is associated with an imbalance between the oestrogen and progesterone production. This last, may drop anyway with the general loss of viability of the ovum and the corpus luteum; but it is much worse with deficient thyroid hormone. Throughout my experience with low thyroid, I have been staggered to find that some women lose their PMT within a month or so of starting their thyroid supplementation - simply the result of improved progesterone production. Where progesterone production in the mid thirties and forties has not been improved by thyroid supplementation, very thoughtful consideration must be given to the provision of progesterone supplementation. The standard way of doing this is by the use of a group of artificial progesterones, which are called progestogens and the synthetic hormone Norithesterone is an example. While these may well be helpful for some women, they have a number of side effects which have made them less and less popular; nevertheless, an alternative must be sought. As oestrogen dominance brings with it its own problems of bloating, weight gain and increased risk of cancer, a progesterone supplementation is essential. Of increasing popularity nowadays is the use of natural progesterone, which is actually extracted from plants and is incorporated in creams which may be simply rubbed into the skin daily. Although establishment thinking is, as might be expected, somewhat suspicious of the natural product, favoring the artificial, very many thousands of women are greatly benefiting from transdermal progesterone (see Appendix D). Another worrying result of a reduction in thyroid function is a reduction of red blood cell production; many people are troubled by a refractory anaemia (when it is unresponsive to treatment), which adds to their general lack of well-being and exhaustion. How much worse is it then, when heavy prolonged periods are added to the problem.. . Iron, folic acid and vitamin C would seem to be essential, especially in the early phases of treatment. A most alarming gap in the management of infertility, is the failure to realize that a prime and a gravely neglected cause is hypothyroidism. It is obvious that there are several ways the healthy ovum can be affected: its production, its maturation, proper fertilization and implantation....... (Pages 135 - 139) " The Great Thyroid Scandal and How to Survive It " by Dr. Barry Durrant-Peatfield MB BS LRCP MRCS, Barons Down Publishing, London, 2002, ___________________________ Ginecol Obstet Mex. 1969 Dec;26(158):777-85. [Report on the relation between limited hypothyroidism and uterine fibromyomatosis] [Article in Spanish] Gutierrez JT. PMID: 5408031 [PubMed - indexed for MEDLINE (Paper can be purchased from PubMed) _____________________ Akush Ginekol (Mosk). 1988 May;(5):46-50. [The reproductive system of patients with disordered thyroid function] [Article in Russian] Sosnova EA. PMID: 3177773 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ___________________________ J Assoc Physicians India. 1993 Feb;41(2):88-90. Comment in: J Assoc Physicians India. 1993 Nov;41(11):761-2. Hypothyroidism presenting with polycystic ovary syndrome. Sridhar GR, Nagamani G. Endocrine & Diabetes Centre, Visakhapatnam. During a 30 months period, two women of primary hypothyroidism (2/13; 1.04%) presented with features of polycystic ovary syndrome (PCOS). In hypothyroidism, sex hormone binding globulin levels are decreased; increased conversion of androstenedione to testosterone, and aromatization to estradiol are present, all these being an exaggeration of biochemical changes characteristic of PCOS. Besides, metabolic clearance rates of androstenedione and estrone, the putative mediators of PCOS, are reduced. Hypothyroidism can either initiate, maintain or worsen the syndrome. Correction of hypothyroidism when present, would therefore form an important aspect in the management of infertility associated with PCOS. Publication Types: Case Reports PMID: 8053991 [PubMed - indexed for MEDLINE] __________________ Pediatr Akus Ginekol. 1968 Sep-Oct;5:55-8. [Function of thyroid gland in uterine fibromyoma] [Article in Ukrainian] Sol's'kii IaP, Chizhova PS, Ivaniuta PI. PMID: 5743398 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _______________________ Akush Ginekol (Mosk). 1970 Oct;46(10):24-7. [Functional status of the thyroid gland in patients with uterine myoma] [Article in Russian] Vasilevskaia LN, Kotliarov EV. PMID: 5519731 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) _________________ Ginecol Obstet Mex. 1974 Jun;35(212):657-80. [Edocrinal study of uterine fibromyoma] [Article in Spanish] Nava y R. PMID: 4138171 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ____________________ Akush Ginekol (Mosk). 1967 Oct;43(9):17-21. [Adrenal cortex and thyroid gland function in patients with myoma of uterus] [Article in Russian] Slepov MI, Novouspenskaia IE. PMID: 5607969 [PubMed - indexed for MEDLINE] (Paper can be purchased from PubMed) ________________ Author: GRIFF T. ROSS, M.D., Date Published: 01-Jan-1958 Publication: Journal of Clinical Endocrinology and Metabolism 18: 492-500, 1958 Title: SEVERE UTERINE BLEEDING AND DEGENERATIVE SKELETAL-MUSCLE CHANGES IN UNRECOGNIZED MYXEDEMA Category: reproductive Keywords: reproductive, problem, ROSS, SEVERE, UTERINE, BLEED, DEGENERATIVE, SKELETAL, MUSCLE, CHANGE, UNRECOGNIZED, MYXEDEMA, treat, women, menstruation, severe, anemia, normal, desiccated, thyroid Text: p 492 ABSTRACT Two cases of severe uterine bleedng associated with unrecognized myxedema (hypothyroidism) are reported. Degenerative changes in skeletal muscles were suggested by the results of electromyographic studies and demonstrated by biopsy of a muscle prior to treatment in one patient. The uterine bleeding stopped promptly and a normal menstrual cycle was re-established in both patients after treatment with desiccated thyroid. DISTURBANCES in thyroidal function in premenopausal women are often associated with abnormalities of menstruation. Either menorrhagia or amenorrhea may develop in patients with spontaneous or postoperative myxedema. However, when amenorrhea occurs in a premenopausal women with the secondary hypothyroidism the diagnosis of hypopituitarism should be considered and excluded. In his book, Means stated: " Menorrhagia may be sufficiently impressive in ordinary myxedema so that in several cases that have come to our attention patients have actually had a dilation and curettage for it when all they needed was desiccated thyroid for treatment. " We are reporting 2 cases of profuse uterine bleeding with severe anemia secondary to unrecognised primary myxedema, in which prompt cessation of uterine bleeding and restoration of normal menstrual cycles followed the oral administration of desiccated thyroid. Significant degenerative changes in the skeletal muscles were suggested by the results of electromyography and were demonstrated by muscle biopsy prior to treatment in one of these patients. p 494 .. ....COMMENT Both these patients were referred for consideration of surgical treatment for intractable profuse uterine bleeding. Severe menorrhagia lasting from p495 six to ten days had been present during the six months preceding the admission of the first patient to the hospital. After the clinical recognition of myxedema, it was realized that the bleeding might be due to the hypothyroidism. For this reason, operation was deferred until the patient could be restored to euthyroid state. After five days of oral treatment with desiccated thyroid, the uterine bleeding ceased. The menstrual pattern subsequently returned to normal with regard to periodicity and flow. Despite the fact that the second patient had noted intermenstrual spotting for many years, the myxedema in all probability began after her last pregnancy in 1950. There was nothing to suggest anterior- pituitary insufficiency, since the patient lactated and cyclic menstrual periods were re-established following parturition. She was extremely exsanguinated on admission, as shown by the clinical picture of mild shock and severe anemia. Her response toe desiccated thyroid was most gratifying, since the uterine bleeding stopped after seven days of therapy. A checkup after three months off treatment revealed that she was clinically euthyroid. A remarkable change had taken place in the facies (Fig. 1). normal menses had returned. __________________ Author: JENNINGS C. LITZENBERG, M.D. Date Published: 01-Jan-1937 Publication: JAMA, 109:1871-1873, 1937 Title: THE ENDOCRINES IN RELATION TO STERILITY AND ABORTION Category: reproductive Keywords: reproductive, problem, LITZENBERG, ENDOCRINE, RELATION, STERILITY, ABORTION, fertile, pregnancy, develop, hormone, fetus, basal, metabolic, rate, menstrual, thyroid, women, normal Text: p1871 The endocrines govern the physiology of reproduction from beginning to end; spermatogenesis, ovogenesis, maturation of the ovum, ovulation, fertilization, preparation of the endometrium for nidation, implantation of the fertilized ovum, placentation, maintenance of pregnancy, development of the fetus, birth and lactation - all are dependent on hormones initiated and controlled by the anterior hypophysis. p1872 .....THE THYROID AND STERILITY Since 1922 I have studied the relation of the basal metabolic rate to sterility, abortions, and menstrual disturbances. In our first small series of sixty-nine consecutive sterile women, in whom no other evidence of myxedema was present, 50 per cent had a low basal rate; adding those who had conceived but aborted the figure was 56 per cent. Carefully supervised thyroid medication resulted in 33.3 per cent conception, 14 per cent of whom aborted. One woman conceived three times under thyroid medication, bringing the percentage of conceptions to 40. In another group of 114 women, 45 per cent of the married women were sterile and 40 per cent of the entire group had functional disturbances of menstruation. In a second series of 137 women, approximately the same figures were obtained, but in addition we found that 63 per cent had abnormal menses (our patients all came from a goiter area). Our third series (including the pervious reports) consists of 255 married women, 49.7 per cent of whom were sterile. Of 332 women, married and unmarried, 33.5 per cent had functional disturbances of menstruation. During the fifteen years of our experience to date (including cases not previously reported) there was a consistent rate of conceptions of 30 per cent in women with low basal rates. Haines and Mussey of the Mayo Clinic confirmed our thyroid treatment of functional menstrual disturbances, saying: " Because of a desire to determine the effectiveness of thyroid medication alone, in the treatment of certain menstrual disturbances, no patient received any other treatment. All were definitely improved; amenorrhea, 72 per cent; oligomenorrhea, 55 per cent; menorrhagia, 73 per cent, and general health, 75 per cent. " Also in this connection Haskins says: " Most gynecologists agree that thus far, of all the gland products, thyroid has proved to be the most useful for a variety of endocrine disturbances, including amenorrhea, oligomenorrhea, menorrhagia, sterility and abortion. " Marine, long ago (1917) when there was scarcely any usable knowledge of the endocrines, declared: " The relation of the thyroid to the sex organs in the female is the most frequent and classical illustration of the interrelation of the function of glands with internal secretions. " adds testimony by saying " The sole endocrine preparation that has proved itself of real value has been thyroid extract, which is of use in patients with lowered basal metabolism. " Novak declared that thyroid medication in sterility and abortion are more often efficacious than any other form of organotherapy. Desiccated thyroid was the first, and is still one of the few successful, substitutional hormone preparations. Perhaps when one gives desiccated thyroid one is doing to the ovaries what the pituitary has failed to do through stimulation of the thyroid gland by means of the thyrotropic hormone. I quote the concluding paragraph of an editorial in THE JOURNAL: These reflections [criticisms of the misuse of sex gland hormones] are not intended to inhibit chemical and biologic studies in accredited laboratories. Neither do they apply to the carefully controlled clinical application of accepted knowledge by competent observers; this is necessary. Rather are they intended (1) to emphasize that there is a great discrepancy between laboratory knowledge of the hormones and their clinical application, (2) to suggest that for the present only those clinicians with facilities for critical study be encouraged to administer the newer endocrine preparations to patients and that these clinicians be urged to publish their negative as well as their positive results, and (3) to suggest that a large group of physicians not represented in either of the groups mentioned cease their undiscriminating injection of unknown substances into unsuspecting patients. Physicians are perhaps cynical because of our limited knowledge of the endocrines and the complexity that faces it, but the tendency is to optimism when it contemplates the accomplishments of the recent past with their great promise for the future. _____________________ Author: RUTH C. FOSTER Date Published: 01-Jan-1939 Publication: ENDOCRINOLOGY 24:383,1939 Title: THYROID IN THE TREATMENT OF MENSTRUAL IRREGULARITIES Category: reproductive Keywords: reproductive, problem, FOSTER, THYROID, TREAT, MENSTRUAL, IRREGULAR, women, period, basal, metabolic, pelvis, metrorrhagia, amenorrhea, bleed, relief, continue, normal, desiccated Text: p383 DURING THE PAST few years we have been impressed by the efficacy of thyroid medication in the treatment of menstrual irregularities. Because our series of cases has shown results similar to those reported by clinicians working elsewhere, it has seemed worth while to summarize our data and present it in confirmation of material published previously. Fifty cases treated with thyroid have been observed for a period of from one to four years. These patients have been seen at least twice a month. Their ages have ranged from 16 to 34, although 41 of the series have been under 22 years of age. All have had complete physical examinations, pelvic studies, and repeated basal metabolic determinations. With a few exceptions, which will be discussed later, only those who showed no pathology in the pelvis have been treated with thyroid. .....Among this group of patients 25 complained of dysmenorrhea which was of sufficient severity to cause repeated absence from classes. Seventeen complained of scanty or delayed menstrual periods with intervals of as long as three months. Thirteen complained of too frequent periods or of inter-menstrual bleeding, while 7 had excessive flow together with the metrorrhagia. There were 5 cases of amenorrhea which was of 7 months to 4 years duration. Four of the patients had normal periods but there was a marked irritability with inability to concentrate for as long as a week prior to the period. p385 Of the 17 cases of oligomenorrhea, all reported definite relief as long as they continued taking thyroid. Several of this group tried going without therapy during the summer vacation but returned in the fall asking to resume treatment because their symptoms had recurred. All stated they felt much better when having their regular periods. .....The group of patients who complained of amenorrhea is small due to the fact that pathology was found to explain the cessation of periods in many of those who had this complaint. Those patients treated were given thyroid because their B.M.R. were low, and they or their parents wished them to receive a trial with thyroid before endometrial biopsies and further studies were made. p386 Those patients complaining of menorrhagia and metrorrhagia responded to thyroid therapy in a most satisfactory manner. The one failure was in a patient who had a large ovarian cyst removed because of prolonged menorrhagia. .....V.C., a university junior 18 years of age, consulted the Student Health Department because of a slight menstrual flow of six weeks duration, early fatigue, and a tendency towards a rapid gain in weight. She stated that her menstrual periods began when she was 13 and that they had always been irregular, occurring at intervals of three weeks to several months (9 months at one time). .....Treatment consisted of 1 to 2 gr. desiccated thyroid daily. The B.M.R. rose to -5, blood pressure to 108/78; the bleeding stopped and apparently normal periods occurred until the dose of thyroid was reduced, when there was a recurrence of the metrorrhagia. This patient has learned that she will have no symptoms I she takes thyroid in sufficient dosage to keep her B.M.R. -5 or above. This has been so consistent in her case that she can accurately predict her B.M.R. will be below these levels when the metrorrhagia recurs. p387 Four patients who complained of marked irritability prior to their periods are included in this series because their complaint was enough to interfere with their ordinary activities, and 3 did have relief with thyroid. Two noted partial relief, enough so that they did not want to stop thyroid medication. One had complete relief and one noted no difference. Thyroid was stopped several times but always with a recurrence of their symptoms. ..... DISCUSSION The explanation for the efficacy of thyroid medication in these cases can only be hypothesized. Experimental work in animals has shown that ablation of the thyroid is followed by an increase in size of the pituitary gland. Microscopic examination of these pituitaries shows hydropic degeneration, which explains the fact that after this procedure glands lose some of their potency. It may follow that in these patients there is an inadequate thyroid secretion resulting in a decrease in potency of the pituitary gland, which in turn causes inadequate gonad stimulation. One might go farther and state that the 4 patients who noted breast engorgement for the first time were having their first normal cycles with luteinization occurring. p388 Some of these problems may be solved by a study of endometrial biopsies before and after treatment. In a group of patients as young as these reported, most of whom are minors, it is difficult to obtain permission for biopsies from the parent, but as the public becomes educated to this procedure more parents should be willing to consent. It is our feeling that a B.M.R. should be obtained in all cases complaining of menstrual irregularities such as those reported above. Providing there is no pelvic pathology or physical condition to explain the symptoms, these patients should probably receive a trial with thyroid before further therapy is undertaken if their metabolic rates are below zero. It is understood that these patients will report periodically to their physicians and that the dose of thyroid will depend upon the individual response. In many cases there will be a complete relief of symptoms with small doses of thyroid although the metabolic rate has not reached what is considered the normal level. There is no way of predicting from the individual B.M.R. the degree of relief to be obtained. SUMMARY Fifty patients with ages ranging from 16 to 34 years were seen because of dysmenorrhea, oligomenorrhea, amenorrhea, metrorrhagia and menorrhagia. All were apparently healthy individuals with normal pelvic findings. These patients had B.M.R. ranging from -1 to -33 with an average of -15. All were treated with desiccated thyroid. Of 25 cases of dysmenorrhea 17 had complete relief, 5 partial, and 3 no relief. Of 4 patients with amenorrhea lasting from 8 months to 4 years only one had relief of her symptoms. Among 13 patients with metrorrhagia 12 had complete relief and of 7 with a menorrhagia 6 had complete relief. It is suggested that a B.M.R. should be determined in those individuals complaining of menstrual irregularities who have no demonstrable pathology to explain their symptoms. A therapeutic trial of thyroid is indicated if the B.M.R. is zero or below. ______________________ Author: BRODA O. BARNES M.D Date Published: 01-Jan-1949 Publication: MEDICINE January, 1949, Vol. 6, No. 1 pp. 33-34 Title: THE TREATMENT OF MENSTRUAL DISORDERS IN GENERAL PRACTISE Category: reproductive Keywords: reproductive, problem, BARNES, TREAT, MENSTRUAL, DISORDER, GENERAL, PRACTISE, thyroid, therapy, improve, patient, Basal, Temperature, relieve, bleed, women Text: The general practitioner can expect about 10 per cent of his patients to complain of menstrual difficulties. .....In 1939 and Thornton reported 50 cases of menstrual irregularities treated with thyroid therapy. Their results were far better than any published before or since. This present report of 143 cases is presented in confirmation of their work, and outlines an inexpensive plan of management which produces gratifying results. .....Control series for a group of cases of this kind are difficult. Each case serves as its own control for the period before therapy. Many of the patients relieved of their symptoms ceased medication and in a few months would have a return of their previous complaints. Thyroid therapy would again correct their menstrual difficulty. In view of the fact that the number of patients who were improved in the present series is almost identical, in proportion, with that of and Thornton in 1939, it seems reasonable to assume that the results are due to the treatment. SUMMARY One hundred forty-three cases of functional menstrual disorders have been studied. Dysmenorrhea, excessive bleeding and irregular menstrual cycles are included. The Basal Temperature usually is subnormal. Thyroid therapy relieves the symptoms in about 90 per cent of these cases. _______________________ Author: JOSEPH C. SCOTT, JR., M.D. Date Published: 01-Jan-1965 Publication: American Journal Obstetrics and Gynecology 90:161-165, 1965 Title: Menstrual patterns in myxedema Category: reproductive Keywords: reproductive, hypo, problem, pattern, myxedema, SCOTT, hypo, gland, menstruation, mild, test, menstrual, thyroid, hormone, menorrhagia, disease Text: 161 HYPOFUNCTION of the thyroid gland produces a broad spectrum of symptoms and signs, often including a change in the menstrual pattern. The various disorders of menstruation which may be associated with myxedema have been documented, but a difference exists in the reported frequency and types of abnormal menstrual pattern. Hypothyroidism has been implicated as the underlying cause of many irregularities of menstruation. .....Generally, it is believed that thyroid hormone is beneficial and its use is indicated only when there is evidence of thyroid hypofunction. A patient may be considered to be mildly hypothyroid by one clinician and euthyroid by another on the basis of only a single interview or test. No single test or procedure will define the status of the thyroid gland. Furthermore, any combination of methods may lead to erroneous interpretation or to inconsistent results. The clinician must have the faculty of correlating the clinical appearance of the patient with the laboratory findings. p 164 .....Comment Menorrhagia, that is, an increase in the amount and duration of menstrual flow, associated with myxedema may be mild, " occult, " or severe. Mild menorrhagia is a source of only minor concern and usually is corrected by better control of the myxedematous state. The term " occult menorrhagia " is warranted in cases in which there is excessive or prolonged menstruation which the patient considers to be normal. In these cases the onset of the menorrhagia has been so insidious that the patient is truly unaware of the change unless questioned closely (Case 2). Severe menorrhagia may require diagnostic curettage in addition to thyroid replacement therapy. Thyroid dysfunction should be considered in evaluation of each case of menstrual irregularity. Our studies reinforce the observations of other authors that menstrual disorders are not unusual in myxedema. A careful gynecologic examination should be performed for each patient suspected of having a thyroid disease. Any menstrual disorder should not be minimized and the possibility of genital malignant disease should be considered. Laboratory studies have greatly aided the clinicians in defining and evaluating thyroid disease states, but the " clinical appearance " of the patient should continue to be a prime factor in evaluation. Diagnostic measures, such as the quantitation of menstrual blood loss by tagging with radioactive chromium, are useful and informative in many patients, but not indispensable. Menorrhagia is the most frequent of the menstrual aberrations which are associated with myxedema. Hypomenorrhea and amenorrhea are much less common, and we have found oligomenorrhea to be rare. p 165 Summary The menstrual patterns of 50 premenopausal myxedematous women between 16 and 40 years of age were evaluated. Abnormal menstrual patterns occurred in 56 per cent of these patients. More than one form of menstrual irregularity was noted in two cases. Menorrhagia and metrorrhagia, alone or combined, constituted the abnormal patterns in 75 per cent of the patients. Amenorrhea occurs infrequently with myxedema. " Occult " menorrhagia should be considered in the evaluation of the patient with thyroid disease. _______________________ Author: Longcope Date Published: 30-Jun-1996 Publication: Werner and lngbar's The Thyroid, Seventh Edition, edited by E. Bravennan and D. Utiger. Lippincott-~ven Publishers, Philadelphia, @ 1996 Title: 71 The Male and Female Reproductive Systems in Hypothyroidism Category: reproductive Keywords: Longcope, reproduction, uterus, ovaries, hypo, thyroid, endometrial, muscle, animal, human, fertility, sexual, vagina, precocious, puberty, fetal, abort, testicular, sperm, libido Text: 849 HYPOTHYROIDISM IN THE FEMALE REPRODUCTIVE SYSTEM Hypothyroidism seems to affect the reproductive system in women more than in men. A review of the normal develop- ment and physiology of the female reproductive system has been given in chapter 47. Animal Studies In sheep, fetal hypothyroidism does not affect reproductive tract development but does result in prolonged gestation despite maternal euthyroidism.l However, in the rat, fetal hypothyroidism results in small ovaries deficient in lipid and cholesterol.2 Thyroidectomy of sexually immature rats results in delayed vaginal opening and sexual maturation; smaller ovaries and follicles than in controls3,4; and uteri and vaginas that are not well developed.5 When adult female rats are rendered hypothyroid their estrous cycles become irregular and their ovaries become atrophic.6 There is an enhanced response to HCG with the development of large cystic ovaries in hypothyroid rats.7 Hypothyroidism in hamsters and cows is associated with abnormal estrous cycles,s.9 and in hypothyroid hens there is a decrease in egg production.9 In the mature female rat, hypothyroidism apparently does not result in sterility but does interfere with gestation, especially in the fIrst half of pregnancy,lO with resorption of the embryo and subsequent reduction in litter size and an increase in stillbirths.ll In hypothyroid sheep, the uterus shows endometrial hyperplasia and smooth muscle hypertrophy, perhaps related to the prolonged estrous noted in hypothyroid ewes.12 Ruh and coworkers 13 reported increased estradiol binding in uteri of hypothyroid rats, but Kirkland and coworkers 14 found a decrease in the uterine response to estrogen in hypothyroid rats. Hypothyroidism inhibits the photoperiod responses and seasonal breeding patterns in sheep and birds.15,16 Human Studies and Clinical Aspects The reproductive tract appears to develop normally in cretins; thus, hypothyroidism during fetal life does not appear to affect the normal .development of the reproductive tract. Hypothyroidism in prepubertal years generally leads to short stature and may lead to a delay in sexual maturity.4 However, an interesting syndrome described by Kendlell and Van Wyk and Grumbach 18 occurs not infrequently: it is characterized by precocious menstruation, galactorrhea, and sella enlargement in girls with juvenile hypothyroidism. The cause is thought to be an overlap in the pituitary production of TSH and gonadotropins, with the latter causing early ovarian secretion of estrogens and subsequent endometrial stimulation with vaginal bleeding. Prolactin levels are elevated, leading to galactorrhea. However, there is no pubertal increase in the adrenal production of androgen precursors, so that axillary and pubic hair are usually not apparent.I8 Therapy with thyroxine in proper dosage results in prompt alleviation of the symptomatology. In adult women, hypothyroidism results in changes in cycle length and amount of bleeding I9-21 and has been reported 850 in association with the ovarian hyperstimulation syndrome.22 Menorrhagia is a frequent complaint and is probably due to estrogen breakthrough bleeding secondary to anovulation, which is frequent in severe hypothyroidism. 19 The anovulation is reflected in the frequent finding of a proliferative endometrium on endometrial biopsy.23 TRa-l and TRBB-1 receptors have been found in human granulosa cells and both triiodothyronine and thyroxine have been found in follicular fluid.24 Earlier work in- dicated that thyroxine enhanced the action of gonadotropins on luteinization and progestin secretion by cultured granulosa cells,25 and it has recently been noted that in a group of infertile women, those with elevated TSH levels had a higher incidence of out-of-phase biopsies than women with normal TSH.26 Ovulation and conception can occur in mild hypothyroidism, but in the past those pregnancies that did occur were often associated with abortions in the first trimester, stillbirths, or prematurity, 19,27 Recent studies indicate these events may be less common but that gestational hypertension occurs often in pregnant women with untreated hypothyroidism.28 Pregnancy occurring in women with myxedema has been reported to be uncommon,27 but this is somewhat hard to document and may be the result of anovulation. The use of L-thyroxine is not helpful in treating euthyroid patients for infertility, menstrual irregularity, or the premenstrual syndrome.29,30 In evaluating the thyroid status of the pregnant woman, the level of TSH is probably the best indicator of changes in thyroid function. Because radioiodine will readily cross the placenta and can cause fetal hypothyroidism, tests involving ra- dioiodine administration to the mother are contraindicated in pregnancy.19 When hypothyroidism is diagnosed during pregnancy, L-thyroxine therapy should be instituted promptly to increase the chances for a normal pregnancy. Although it has been thought that little L-thyroxine would cross the placenta,19 it appears that L-thyroxine will cross the placenta in modest amounts,31 at least early in pregnancy. Women who have required thyroid hormone therapy prior to pregnancy should continue with such therapy throughout the pregnancy. How- ever, recent evidence indicates that the hormone dose needs to be increased during pregnancy, even though adequate replacement had been given before conception.31 It is advisable to monitor the serum TSH concentration at least once during each trimester to ensure that an adequate dose is received. Thyroid disease during and after pregnancy is discussed in detail in chapter 89. Some myxedematous women will present with amenorrhea and galactorrhea and elevated serum prolactin concentrations.19 Thus, thyroid evaluation should be an essential part of the work-up in any person with galactorrhea. If hypothyroidism is the cause, the amenorrhea and galactorrhea and elevated serum prolactin will disappear promptly with thyroxine therapy.32 There is an increased incidence of Hashimoto's thyroiditis in individuals with 's syndrome,33 and, although a chromosomal linkage between autoimmtme disease and the X- chromosome has been suggested, this has not been confirmed.34 Inherited abnormalities in serum thyroxine-binding globulin (TBG) are X-linked, and patients with 's syndrome may ,have low serum TBG values.35 Women with hypothyroidism have decreased metabolic clearance rates of androstenedione and estrone and increased peripheral aromatization.36 The ratio of 5a/5B metabolites of androgens is decreased in hypothyroid women, and there is an increase in the excretion of estriol and a decrease in the excretion of 2-oxygenated estrogens.37 In summary, hypothyroidism in girls can cause alterations in the pubertal process; this is usually a delay, but occasionally it can result in pseudoprecocious puberty. In mature women, hypothyroidism usually is associated with abnormal menstrual cycles, especially anovulatory cycles, and an increase in fetal wastage. HYPOTHYROIDISM IN THE MALE EPRODUCTIVE SYSTEM The normal development and physiology of the male reproductive system has been described in chapter 47. Although less common in men than in women, hypothyroidism, induced or spontaneous, affects the male reproductive tract in a number of ways depending, in part, on the age of onset. Animal Studies The fetal thyroid starts functioning about the same time as the gonads.38 Although thyroid hormones play role in sex differentiation and gonadal maturation in fish and amphibians,39 they do not appear to be necessary for the normal development of the reproductive tract in mammals. 1 However, hypothyroidism, induced or occurring soon after birth, is associated with a marked delay in sexual maturation and development.40 When rats are made hypothyroid with propylthiouracil administered from birth to 24 to 26 days of age, testicular size is decreased, Sertoli cell differentiation is retarded, and the time of Sertoli cell proliferation is prolonged.4].42 As these rats become older and euthyroid, then the testis size, Sertoli cell number, and sperm production are all increased.41, Leydig cell numbers are increased but testosterone secretion per cell is decreased, although total testosterone secretion remains the same as controls.43 FSH and LH levels tend to remain low throughout treatment and recovery periods, whereas inhibin levels are elevated.41 However, if hypothyroidism persists untreated, there is an arrest of sexual maturity with absent libido and ejaculate.44 The interstitial cells of the testis are reduced in number and the arrested growth of the accessory male sex organs indicates a decrease in the production of testosterone.44 The longer the hypothyroidism persists, the greater the degree of damage to the testes,44 although genetically induced hypothyroidism in male mice is associated with normal fertility .45 In the adult ram, hypothyroidism is associated widl a decrease in testosterone concentration but normal spermatogenesis.46 In the mature male rat, the induction of hypothyroidism has little effect on the pathology of the testes, sperlllatogenesis, or serum testos- terone concentrations.47 Thus, it would appear that hypothyroidism can affect the immature, but not the mature, testis. Human Studies and Clinical Aspects The development of hypothyroidism in the male fetus does not appear to affect the reproductive system. Cretins are usually born with a normally developed reproductive tract. The presence of hypothyroidism in the prepubescent years usually results in a delay of sexual maturation and of the whole pre-pubertal process, which can be overcome by the administration of adequate doses of thyroxine. However, in some instances, hypothyroidism can result in precocious pseudopuberty marked by the early development of external genitalia, but without the appearance of axillary and pubic hair. 48 This syndrome probably results from an increased secretion of gonadotropins along with TSH from the enlarged pituitary.48 In men, hypothyroidism has been suggested as a cause of infertility,49 but there is considerable disagreement with this suggestion. 50 If an infertile man is found to be hypothyroid, one should suspect secondary hypothyroidism and pituitary disease rather than primary myxedema, and there is no reason to treat infertile euthyroid men with thyroid hormone.50 In hypothyroid men, testicular size and potency may be normal and, despite early reports of defective spermatogenesis in hypothyroidism, 51 semen analysis is usually normal.52 Wortsman and colleagues reported that myxedema was often associated with infertility and impotence, but in this report the impotence did not improve when the men became euthyroid.49 In addition, there was a decrease in serum testosterone and free testosterone and, in the men who were not over-weight, an increase in sex hormone-binding globulin. It should be noted that sex hormone-binding globulin levels have also been reported as both decreased53 and normal 54 in hypothyroid men. Many men with hypothyroidism do note a decrease in libido, but this is probably a nonspecific disease-related complaint, which disappears when the euthyroid state is achieved with thyroid replacement therapy. Variations in testis size and histology have been noted in autopsy material,55,56 and De La BaIze and coworkers 51 noted Leydig cell hyperplasia and tubular hyalinization. There is a marked decrease in the 5a/5B ratio of the metabolites of androstenedione and testosterone, which is the reverse of that seen in hyperthyroidism 57 In summary, although hypothyroidism in boys frequently interferes with the normal pubertal process, the development of hypothyroidism in men has a less clear-cut effect on the reproductive system. References - not thoroughly checked 1. Hopkins PS, Thorburn GD. The effects of foetal thyroidectomy on the devel2. Leathem JH. Extragonadal factors in reproduction. In: Lloyd CW, ed. Recent progress in the endocrinology of reproduction. New York: Academic Press, 1959:179 3. Leathem]H. Role of the thyroid. In: Balin H, Glasser S, eds. Re- productive biology. Amsterdam: Excerpta Medica, 1972:23 4. Hayles AB, Cloutire MD. Clinical hypothyroidism in the young— a second look. Symp Endocr Disorders 1972:56:871 5. Scow RO, Simpson ME. Thyroidectomy in the newborn rat. Anat Rec 1945;91:209 6. Ortega E, E, Ruiz E. Activity of the hypothalamo- pituitary ovarian axis in hypothyroid rats with or without tri- iodothyronine replacement. Life Sci 1990;46:391 7. Takacs-Jarrett M, Broot BC. Steroid secretion by follicles and cysts from the hypothyroid, hCG-treated rat. Sac Experimental BioI Med 1994;207:62 8. Vriend J, Bertalanffy FD, Ralcewicz TA. The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in fe- male Syrian hamsters. Bioi Reprod 1987;36:719 9. Maqsood M. Thyroid functions in relation to reproduction of mammals and birds. Bioi Rev 1952;27:281 10. Bonet B, Herrera E. Maternal hypothyroidism during the first half of gestation compromises normal catabolic adaptations of late gestation in the rat. Endocrinology 1991;129:210 11. Rao PM, PandaJN. Uterine enzyme changes in thyroidectomized rats at parturition. J Reprod FertiI1981;61:109 12. Nesbitt REL, Abdul-Karim RW, Prior JT, TF, Rourke JE. Study of the effect of experimentally induced endocrine insults upon pregnant and nonpregnant ewes. m. ACfH and propyl- thiouracil administration and the production of polycystic ovaries. Fertil Steril1967;18:739 13. Ruh MF, Ruh TS, Klitgaard HM. Uptake and retention of estro- gens by uteri from rats in various thyroid states. Proc Soc Bioi Med 1970;134:558 14. Kirkland JL, Gardner RM, Mukku VR, Akhtar M, Stancel GM. Hormonal control of uterine growth: The effect of hypothy- roidism on estrogen-stimulated cell division. Endocrinology 1981;108:2346 15. Moenter SM, Woodfill CJI, Karsch FJ. Role of the thyroid gland in seasonal reproduction: Thyroidectomy blocks seasonal suppres- sion of reproductive neuroendocrine activity in ewes. En- docrinology 1991;128:1337 16. Dawson A. Thyroidectomy progressively renders the reproduc- tive system of starlings (Sturnus vulgaris) unresponsive to changes in daylengtll. J EndocrinoI1993;139:51 17. Kendle F. Case of precocious puberty in a female cretin. Br Med J 1905;1:246 18. Van Wyk J, Grumbach MM. Syndrome of precocious menstrua- tion and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap pituitary feedback. J Pediatr 1960;57:416 19. R, Reid RL. Thyroid disease and reproductive dysfunc- tion: a review. Obstet GynecoI1987;70:789 20. Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. AmJ Obstet GynecoI1989;160:673 21. Higham]M, Shaw RW. TIle effect of thyroxine replacement on menstrual blood loss in a hypothyroid patient. Br J Obstet Gy- naecol 1992;99:695 22. Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimu- lation syndrome associated with hypothyroidism. Am J Obstet GynecoI1989;160:1220 23. Goldsmith RE, Sturgis SH, Lerman J,. Stanbury JB. The menstrual pattern in thyroid disease. J Clin Endocrinol Metab 1952;12:846 24. Wakim AN, Polizotto SL, Buffo ML, Marrert;> MA, Burholt DR. Thyroid hormones in human follicular fluid and thyroid hor- mone receptors in human granulosa cells. Fertil Steril 1993;59:1187 25. Channing CP, Tsai V, Sachs D. Role of insulin, thyroxine and cor- tisol in luteinization of porcine granulosa cells grown in chemi- cally defined media. Bioi Reprod 1976;15:235 26. Gerhard I, Becker T, Eggert-Kruse W, Klinga K, Runnebaum B. Thyroid and ovarian function in infertile women. Hum Reprod 1991;6:338 27. LE, Leveno KJ, Cunningham FG. Hypothyroidism compli- cating pregnancy. Obstet Gynecol1988;72:108 28. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JR. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993;81:349 29. Nikolaj TF, Mulligan GM, Gribble RK, Harkins PG, Meier PR, RC. Thyroid function and treatment in premenstrual syn- drome.J Clin Endocrinol Metab 1990;70:1108 30. Roti E, Minelli R, Gardini E, Braverman LE. The use and misuse of thyroid hormone. Endocr Rev 1993;14:401 852 31. Burrow GN, Fisher DA, Larsen PRo Maternal and fetal thyroid function. N EnglJ Med 1994;331:1072 32. CRW, Forsyth lA, Besser GM. Amenorrhea, galactorrhea and primary hypothyroidism with high circulating levels of pro- lactin. Br MedJ 1971;3:462 33. Van Campenhout J, Van J, Antaki A, Rasio E. Diabetes mellitus and thyroid autoimmunity in gonadal dysgenesis. Fertil Steril 1973;24:1 34. Vallotton ME, Foibes AP. Autoimmunity in gonadal dysgenesis and Klinefelter's syndrome. Lancet 1967;1:648 35. Refetoff S, Selenkow HA. Familial thyroxine-binding globulin deficiency in a patient with 's syndrome (XO). N Engl J Med 1968;278:1081 36. Longcope C, Abend S, Braverman LE, Emerson CR. Androstene- dione and estrone dynamics in hypothyroid women. J Clin En- docrinol Metab 1990;70:903 37. Gallagher TF, Fukushima DK, Noguchi S, et al. Recent studies in steroid hormone metabolism in man. Recent prog Horm Res 1966;22:283 38. Saenger P. Abnormal sex differentiation. J Pediatr 1984;104:1 39. Lynn WG. The thyroid gland and reproduction in cold blooded vertebrates. Proceedings of the Fifth Mid-West Conference Thy- roid 1969;17 40. Palmero S, de Marchis M, Gallo G, Fugassa E. Thyroid hormone affects the development of Sertoli cell function in the rat. J En- docrinoI1989;123:105 41. Kirby JD, Jetton AE, Cooke PS, et al. Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced in- crease in adult testicular size and sperm production in the rat. Endocrinology 1992;131:559 42. Van Haaster LH, de Jong PH, Docter R, De Rooij DG. The effect of hypothyroidism on Sertoli cell proliferation and differentia- tion and hormone levels during testicular development in the rat. Endocrinology 1992;131:1574 43. Hardy MP, Kirby]D, Hess RA, Cooke PS. Leydig cells mcrease their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 1993;132:2417 44. Gomes WR. Metabolic and regulatory hormones influencing testis function. In: AD, Gomes WR, Vandemark NL, eds. The testis. Vol III. Influencing factors. New York: Academic Press, 1970:67 45. Chubb C, Henry L. The fertility of hypothyroid male mice. J Re- prod Fertil1988;83:819 46. dIandrasekhar Y, Holland MK, D'Occhio Mj, Setchell BP. Sper- matogenesis, seminal characteristics and reproductive homlone levels in mature rams with induced hYPQthyroidism and hyper- thyroidism. J EndocrinoI1985;105:39 47. Weiss SR, Burns JM. The effect of acute treatment with two goitrogens on plasma thyroid hormones, testosterone and testic- ular morphology in adult male rats. Comp Biochem Physiol (A) 1988;90A:449 48. Castro-Magana M, Angulo M, Canas A, Sharp A, Fuentes B. Hy- pothalamic-pituitary gonadal axis in boys with primary hypothy- roidism and macroorchidism. J Pediatr 1988;112:397 49. Wortsman J, Rosner W, Dufau ML. Abnormal testicular func- tion in men with primary hypothyroidism. Am J Med 1987; 82:207 50. Steinberger E. The thyroid gland in male infertility. In: C-R, Mastroianni LJr, Amelar R, Dubin 1, eds. Current therapy of infertility 1982-1983. St Louis: CV Mosby, 1982:15 51. De La BaIze FA, Arrilloga F, Mancini RE. Male hypogonadism in hypothyroidism: a study of six cases. J Clin Endocrinol Metab 1962;22:212 52. Griboff S. Semen analysis in myxedema. Fertil Sterill962;13:436 53. Cavaliere H, Abelin N, Medeiros-Neto G. Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. J AndroI1988;9:215 54. De Nayer P, Lambot MP, Desmons MC, Rennotte B, Malvaux P, Beckers C. Sex homlone-binding protein in hyperthyroxinemic patients. A discriminator for thyroid status in thyroid hormone resistance and familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab 1986;62:1309 55. s RC, son SD. Pathologic changes in adult myxedema: survey of 10 necropsies. j Clin Endocrinol Metab 1957;17:1354 56. Marine D. Changes in the interstitial cells of the testis in Gull's disease. Arch PathoI1939;28:65 ____________________________ Author: Sheldon S. StofIer. MD Date Published: 01-Jan-1982 Publication: POSTGRADUATE MEDICINE. VOL 72/NO 2/AUGUST 1982 Title: Menstrual disorders and mild thyroid insufficiency Intriguing cases suggesting an association Category: reproductive Keywords: reproductive, problem, StofIer, Menstrual, disorder, mild, thyroid, insufficiency, case, suggest, association, pathology, patient, treat, levothyroxine, hypo, hyper, TSH, TRH Text: Should patients with menstrual dysfunction but without obvious uterine pathology be considered for thyrotoxin-releasing hormone (TRH) testing? In several cases described here. an apparent relationship between menstrual disturbance and minimal thyroid insufficiency was documented by the patients' dramatic response to treatment with levothyroxine. The association of overt hypothyroidism or hyperthyroidism with menstrual disturbance and infertility is well known.15 However, menstrual disturbance may also be related to minimal thyroid insufficiency, as the following cases suggest. The past ten years have brought enonnous advances in the ability to diagnose mild thyroid dysfunction. The introduction of serum thyroxine and serum thyroid -stimulating hormone (TSH) radioimmunoassays has increased the sensitivity and specificity of thyroid function testing. The serum TSH assay has been shown to be a sensitive indicator of diminished thyroid functional reserve. since TSH levels become elevated before circulating serum thyroxine levels fall below the normal range 6, Thyrotropin-releasing hormone (TRH) is a simple tripeptide nonnally found in the hypothalamus. Its availability in synthetic fonn, protirelin (Thypinone, Relefact TRH), has provided a convenient provocative test of pituitary TSH reserve and has further extended the sensitivity of thyroid testing. In fact, this TRH test is so sensitive that results may be markedly abnormal in patients with no signs or symptoms of thyroid disease.6 Patients with minimal impairment of thyroid functional reserve who have normal serum thyroxine and normal baseline serum TSH levels may have an augmented TSH response to TRH administration.6 76 76 Table 1. Results of thyroid function studies in four patients with menstrual disturbance treated by levothyroxine therapy Case Time of testing Thyroid function study FTI* Baseline TRH:+ TSHt 1 Initial study 2.2 6.0 58.0 After26mo of treatment 2.9 3.0 11.7 2 Initial study 1.9 7.1 57.3 After 6 mo of treatment 3.5 1.6 1.8 3 Initial study 1.7 Two years later 2.1 7.2 52.9 After 3 mo of treatment 2.0 1.2 After 21 mo of treatment 2.6 2.8 14.3 4 Initial study 1.8 9.3 >80 After2 mo of treatment 3.8 3.0 6.1 After 14 mo of treatment 1.7 16.4 >80 After 2 mo of increased 3.6 2.5 2.5 dosage * Free thyroxine index (total T4 x T3 resin uptake). normal range 1.4-4.0 +Thyroid-stimulating hormone by radioimmunoassay, normal <8.0 uU/mc tThyrotropin-releasing hormone test (serum TSH rise 20 min after administration of 100 ug TRH), normal range 2-20 uUI ml 80 ...... Discussion In the past, when thyroid test-ng was nonspecific, inaccurate, and insensitive, desiccated thyroid tablets were often given empirically to women with menstrual dysfunction and/ or infertility. Some of these patients may have improved, reinforcing this unscientific and currently unjustifiable approach. At least a portion of these women may have actually had subclinical, and at that time undetectable, thyroid insufficiency. ...... Recently, I encountered a 32 year-old patient with evidence of very mild thyroid insufficiency who had undergone hysterectomy four years before because of troublesome hypermenonorrhea The patient had a diffuse goiter 11/2 times normal size, and antimicrbsomal antibodies were positive at 1:6,400 dilution. Serum FTI was 1.5, baseline serum TSH was 6.3 µU/m1, and serum TSH 20 minutes after TRH administration was 60.7 µU/m1. The pathology report revealed a normal-sized uterus With a predominantly proliferative endometrium and a normal myometrium. Although mild thyroid dysfunction cannot be proven responsible for this patient's abnormal menstrual bleeding, one wonders if TRH testing could have avoided the need for hysterectomy in this case and perhaps in similar cases. ...... 82 ...... Recommendations Based on my experience, I would recommend that patients \vith long- standing menstrual dysfunction without obvious uterine pathology be considered for TRH testing. Such testing would be especially fruitful in patients with goiter, high-nrmal baseline serum TSH value, or family history of thyroid disease. I would certainly not encourage empirical use of thyroid hormone in such a patient population without appropriate testing. Because mild thyroid insufficiency is so easily treated, TRH testing and atrial of thyroid hormone therapy, if .indicated, should be considered in difficult cases of menstrual dysfunction prior to hysterectomy. Summary Three cases of menstrual disturbance possibly related to minimal thyroid insufficiency are reported. In all cases, tltyrotropin- releasing hormone testing was sensitive enough to detect evidence of tltyroid abnormality .Without exception, treatment with levothyroxine caused a dramatic end to menstrual difficulty. In two of these cases, levotltyroxine tlterapy was discontinued and the menstrual abnormality returned. Resumption of levotltyroxine treatment led to prompt retum of normal menstruation. A fourth case is presented which suggests tltat placebo effect alone is probably not responsible for the observed menstrual improvement. It is possible that minimal thyroid insufficiency can lead to marked menstrual disturbance. References I. Goldsmith RE. Sturgis SH. Lennan J. et a!. The menstrual pattern in thyroid disease J Clin Endocrinol Metab 1952 12: 846-55 2. Distiller LA. Sage1 J. Morley JE. et a!. Assess ment of pituitary gonadotropin reserve using luteinizing hormone releasing hormone (LRH) in states of altered thyroid function J Clin Endocrinol Metab 1975:40, 512-15 3. Keye WR. Yuen BH. KnopfRF. et a!. Amenorrhea yperprolactinemia, and pituitary enlargement secondary to primary hypothyroidism Obstet Gyneco 1976:48,697-702 4. Van Wyk JJ. Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism an example of hormonal overlap in pituitary feedback J Pediatr 1960:57,416-35 5. Tolis G. Hoyte K. McKenzie JM. et al. Clinical.biochemical and rndlologic reversibility of hyperprolactinemic galactorrhea.amenorrhea and abnorma sella by thyroxine in a patient with primary hypothyraidisrn Am J Obstet Gynecol 1978:131, 850-2 6. Ingbar SH. Woeber KA. The thyroid gland In: Willams R. ed, Textbook of endocrinology 6th ed Philadelphia WB Saunders, 1981: 117- 247 7. Buchanan GC. Tredway DR. Pittard JC. et a!.Gonadotropin secretion and hypothyroidism Obstet Gynecol 1977: 50,392-6 S. CoUu R. Abnormal pi tui tary hormone response to thyrotropin- reieasing hormone an index. of central nerve system dysfunctlon In Tolis G, Labrle, F JB, et al. eds Cllnical neuroendocrinology a pathophysiological approach New York Raven Press 1979: 129-37 9. Snyder PJ. s LS. Utige RD et al. Thyroid hormone inhibitlon of the prolactin response to thyrotropin-releasing hormone J Clin Invest 1973: 52,2324-9 10. Tolls G. Prolactin physiology and pathology In: Krieger DT JC eds Neuroendocrinology Sunderland. MA Sinauer Assoc, 1980: 34,322-8 11. Powers JM. Block MB. Primary hypothyroidlsm with reversible hypeprolactinemia and pituitary enlargement Ariz Med 1989:37, 256-8 12. Stoffer SS. McKee1 DW Jr. Randall RV, et a!. Pituilary prolactin cell hypetplasia with autonomous prolactin secretlon and primary hypothytoidism Fertil Steril 1981: 36,682-5 __________________ Author: Luoto R Date Published: 27-Jun-1997 Publication: Int J Epidemiol 1997 Jun;26(3):476-83 Title: Hysterectomy and subsequent risk of cancer. Category: reproductive Keywords: Luoto, Hysterectomy, subsequent, risk, cancer, Elevate, papillary, thyroid, follow, reproductive, endocrinological, cause, high, breast, peri, retrospective, study, menopause, total, pre Text: BACKGROUND: The objective of this retrospective cohort study was to assess the effect of hysterectomy on subsequent risk of cancer among 25,382 hysterectomized and a similar number of non- hysterectomized control women, registered in 1963-1976 in the Mass Screening Registry (MSR). METHODS: Cancer cases were obtained from the Finnish Cancer Registry (FCR) and standardized incidence ratio (SIR); the expected number of cases based on cancer incidence rates of the Finnish female population in 1967-1993, was used. Relative risk (RR) was calculated as SIR among the hysterectomized relative to non-hysterectomized women, adjusted for follow-up, education and parity. RESULTS: The RR estimates of non-genital cancers among women with any hysterectomy were approximately 5% higher than in the non- hysterectomized cohort. Relative risks of rectal cancer (RR = 1.4, 95% confidence interval [CI]: 1.0-1.8) and thyroid cancer (RR = 2.1, 95% CI; 1.5-3.1) were significant and largest among women who had undergone total hysterectomy pre- or perimenopausally. Relative risk estimates of breast cancer were close to unity. CONCLUSIONS: Hysterectomy is not associated with any substantial protective or promoting effect on cancers in general. Elevated risk of papillary thyroid cancer following hysterectomy is biologically plausible, as there are reproductive and endocrinological causes of thyroid cancer. National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland. PMID: 9222770 [PubMed - indexed for MEDLINE] _____________________ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 19, 2005 Report Share Posted March 19, 2005 Hello Tish and thank you so much! I just knew I'd find some common sense and clear information on this forum. Little did I know that this condition was connected with hypothyroidism (I just thought I was estrogen dominant) so I will relish all these articles. I started the progesterone cream in December and was diagnosed with multi-fibroids in January, so I was afraid that the prog. caused them. But the truth is, I've been hypothyroid for at least 10 years, perhaps my entire adult life, if not earlier. Always, always had menstrual problems, heavy bleeding, prolonged cycles, pain for two years, and now this. Funny thing is, I've felt pressure too on the bowel/back (and on the bladder too sometimes) for almost 2 yrs. and the doctors can't find a connection. Even had a complete colonoscopy & barrium x-ray. Talk about gross, sorry. I don't think I'm on my optimal dose of Armour yet. Because I was undertreated w/T4 synthetics for so long, things are in bad condition -- my cells, adrenals, low ferritin, B12, folic acid, etc., and I've had some resistance and other issues so I've had to build slowly. I'm on 2 grains and feel like my body is begging for more. Thank you so much for letting me know that I could be on my way to feeling better and there's a chance for a brighter future. One more thing Tish, based on your experience and knowledge, would you recommend the myomectomy? I know that all of the fibroids can't be removed, because some are growing into the wall of the uterus, but most can. But there are risks. Whew, this is a busy board! > > Since my story is kind of gross, hope you don't mind if I send it to > yu personally. Gosh are doctors stupid or what. Sure fibroids can > cause pain. I was on fibroid newsgroups for about 3 years and there > was pain all over the place. First off they stretch and distort the > uterus and pull the ligaments that hold the uterus and other organs > in place. Then, if you've had two Laps, you might have some > adhesions. They can definitely cause pain. Then, fibroids sometimes > die and this will cause severe pain. (See Stanley West's " The > Hysterectomy Hoax. " He talks about that.) > > I had them for over 6 years and they got huge, 20 week pregnancy. I > had them all removed with mymectomy. But, because I was still an > undiagnosed hypo, I grew two more small ones. Hypothyroidism causes > the uterus to be highly sensitive to estrogen and causes high > estrogen levels. Adrenal problems related to hypothyroidism seem to > increase estrogen sensitivity in tissues. hypothyroidism also lowers > immune function so you don't make natural killer cells that attack > tumors. But, since I have been on 3-3/4 grains of Armour, they have > stoped growing. I've had these for about 3 years. They can be quite > uncomfortable depending on where they are located and their size. My > big ones put pressure on my bowel and that was what drove me to > surgery. I felt uncomfortable pressure and eventually they > interfered with my bowel function and I was spending large amounts > of time in the bathroom. One time back then, I developed a severe > pain from one on the right side. I could hardly walk for two weeks. > It was probably one that died. They are known to outgrow their blood > supply and then they die and are reabsorbed. > > There is a lot of debate about progesterone cream and fibroids. The > drug RU486 is being studied to shrink fibroids. It works by dropping > progesterone levels to almost nothing. RU486 also raises natural > killer cell levels and DHEA levels. I used progesterone cream for > about two years while I had fibroids and It did not slow them down. > I could not verify if it made them grow faster or not. It made me > feel better, but the fibroids kept growing. The jury is really still > out on progesterone. Dr. Lee says it will get rid of them, but I > have not seen any reports of this happening on the newsgroups I was > on. Some people think Uterine Fibroid Embolization is great, but > while I was on the newsgroups, there was a disturbing number of > reports starting to come in that this proceedure did not last and > they would start to grow again. Then people were forced into > myomectomies. But, the UFE proceedure left a lot of adhesions that > made myomectomy difficult sometimes. > > In my book if you feel pain, then you have pain. Doesn't matter what > doctors think. I ended up flying to Boston for surgery with a great > doctor, Dr. Levine. Because mine were so big, hardly any > regular doctor could do a myomectomy. Dr. Levine uses bloodless > surgery and I did not need a blood transfusion for my surgery. But, > I can't help but think that if I had had sufficient thyroid, I wuld > have never needed surgery. Fibroids are very rare in well treated > thyroid patients. > > Tish > ____________________ > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 19, 2005 Report Share Posted March 19, 2005 Okay I have remembered another thing from " Your Bodies Many Cries for Water. " He also states that you should not drink coffee or tea, but if you cannot help yourself he suggests that you drink more water. I am not sure about the amount but for sure it would be for every cup at least two cups of water. It is probably more like four cups. Now really I am gone for the day . . . LOL Sheila Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 19, 2005 Report Share Posted March 19, 2005 Your absolutely right Sheila, I'm absolutely wrong. Re: Hello everyone & fibroids question I had an answer ready for this and went to post message help to see about a spell check and lost my answer. BOOOO HOOOOO In a nutshell, I don't see how you can figure that just because you weren't drinking coffee and had fibroid problems that coffee isn't a contributing factor with other people. Not everyone reacts the same. I know people who have had fibrous breasts, and claim that to quit drinking coffee was the cure. I drink approximately three cups of coffee per day and do not have fibroid problems. But in no way would I say that other people would/wouldn't have the same result. Are you perhaps a coke, Pepsi, mountain dew drinker, or orange pekoe tea? All of those have caffeine in them and that is supposed to be the culprit in coffee that causes fibroids. With that said I am not naive enough to think that caffeine is the only cause of fibroids. Sheila > Hate to shoot this theory down, but coffee can't be the reason for fibroids. I was diagnosed with fibroids when I was made very hypo from too many anti thyroid drugs while being treated for hyperT/Graves. My periods got to be very crazy, like every 17 days, then every other month. The Gyn-Ob dr is the one who was appalled at my treatment by a top dr here in Houston, and the hypo was causing all my female woes. > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 20, 2005 Report Share Posted March 20, 2005 I know that all of the fibroids can't > be removed, because some are growing into the wall of the uterus, _________________________ This is not true. The fibroids in the wall of the uterus are not difficult to remove for the doctors with the proper skills. One thing I learned in all my years of research and fighting being forced into a hysterectomy is that there are only maybe 50 to 100 doctors in the US who know how to do a proper myomectomy. The story about fibroids in the wall being impossible to remove is a very common one, usually given by the less skilled doctors, who would prefer to convince you to do the very simple hysterectomy. Good skill is needed to do a proper myomectomy to control bleeding. Fibroids actually have a kind of capsule around them and they separate out from the uterus quite easily. The doctor simply makes an incision in the area and closes off the blood supply to the fibroid (one or two veins) and sort of pops out the fibroid. They are not like some cancer imbedded tightly in the uterine wall, but are separate very firm tumors that cleave easily away from the muscle in the uterine wall. The difficulty is that the vast majority of doctors do not have training in controlling blood loss in this surgery. It can get out of control on them. But, there are some very highly skilled doctors in the US who use blood recycling equipment that saves lost blood, cleans it and puts it back into you. The result is that very little blood is lost in the proceedure, which is the main worry of regular doctors. These doctors are also skilled in performing the proceedure in ways that really minimizes blood loss. If bleeding gets out of control with a less skilled doctor, there is an increase in the risk of adhesions as well. All these things together are what makes your regular gyno or fertility specialist afraid to tackle multiple and large fibroids. So, they make up all kinds of stories to convince the patient to go for hysterectomy, which a monkey could do. Because so many women have trouble finding a skilled doctor, who won't put them at risk, I started keeping a list of doctors whomen had good experiences with. I put it up on the web. This list is old and has not been updated in about 3 years. But, there are some great doctor on it. The best ones are the ones who know how to do large fibroids. They are the ones who use blood sparing techniques. Here is my old list: http://www.academicmultimediaservices.com/art/Docs.html Some of the bad doctors want to put women on Lupron before doing surgery. Stay away from these. They feel Luporn helps control bleeding. Lupron is a dangerous and very expensive drug, not approved by the FDA for this use due to the dangers and the fact that it worsens the outcome of surgery. It destroys the capsule around fibroids so the doctor cannot tell the difference between fibroid and uterine wall. It also results in a higher rate of regrowth and complications in surgery, not to mention the damage this drug does to your health. Some people have permanent severe bone pain and health problems from this drug. For me, Myomectomy was my best choice. But, if you can hold out long enough to get your thyroid dose up to 3 grains or more or wherever it is best for you, I think your problem will deminish greatly. Fibroids take about 3 years to shrink, but the symptoms should dissapear when thyroid is optimized. I would have preferred to not have this major surgery and to have had my hypothyroidism discovered. But, my surgery was very successful and it took two years for just two small fibroids to appear. I was hypo all this time and I know that is why two grew again. The regrowth rate following a myomectomy is only 25% and 75% of those never have any more problems after a good myomectomy. This means that if the fibroids do regrow, they usually are not a problem. Tish Tish Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 20, 2005 Report Share Posted March 20, 2005 That is very interesting. And you are the 2nd person to say that there can be a lot of blood loss with a myomectomy. My gyn did not mention that. She said it was a very simple procedure, similar to a simple D&C, and that I would be back on my feet in a couple days. Thank you for the list of specialists. I'm thinking more along the lines of getting a 2nd opinion from someone who is considered an expert in this field. Anyway, my doctor is anti-hysterectomy, even though I am so past having children and my uterus is enlarged and lumpy with tumors, and I have wanted her to consider just taking it out, if it will mean getting rid of this chronic pain. Have you heard of a Dr. R. lin, at Baylor in Houston? A person on another forum recommends him. I have a copy of an interview she sent me, but I have no idea how to attach a pdf file! I am hesitant to go through a 3rd surgery with someone who is not considered an expert in this field. I'll also ask my thyroid doctor if he thinks this problem might improve with optimal Armour treatment. I didn't even know that was a possibility, but it would be great! Thanks, > > I know that all of the fibroids can't > > be removed, because some are growing into the wall of the uterus, > _________________________ > > This is not true. The fibroids in the wall of the uterus are not > difficult to remove for the doctors with the proper skills. One > thing I learned in all my years of research and fighting being > forced into a hysterectomy is that there are only maybe 50 to 100 > doctors in the US who know how to do a proper myomectomy. The story > about fibroids in the wall being impossible to remove is a very > common one, usually given by the less skilled doctors, who would > prefer to convince you to do the very simple hysterectomy. > > Good skill is needed to do a proper myomectomy to control bleeding. > Fibroids actually have a kind of capsule around them and they > separate out from the uterus quite easily. The doctor simply makes > an incision in the area and closes off the blood supply to the > fibroid (one or two veins) and sort of pops out the fibroid. They > are not like some cancer imbedded tightly in the uterine wall, but > are separate very firm tumors that cleave easily away from the > muscle in the uterine wall. > > The difficulty is that the vast majority of doctors do not have > training in controlling blood loss in this surgery. It can get out > of control on them. But, there are some very highly skilled doctors > in the US who use blood recycling equipment that saves lost blood, > cleans it and puts it back into you. The result is that very little > blood is lost in the proceedure, which is the main worry of regular > doctors. These doctors are also skilled in performing the proceedure > in ways that really minimizes blood loss. If bleeding gets out of > control with a less skilled doctor, there is an increase in the risk > of adhesions as well. All these things together are what makes your > regular gyno or fertility specialist afraid to tackle multiple and > large fibroids. So, they make up all kinds of stories to convince > the patient to go for hysterectomy, which a monkey could do. > > Because so many women have trouble finding a skilled doctor, who > won't put them at risk, I started keeping a list of doctors whomen > had good experiences with. I put it up on the web. This list is old > and has not been updated in about 3 years. But, there are some great > doctor on it. The best ones are the ones who know how to do large > fibroids. They are the ones who use blood sparing techniques. Here > is my old list: > > http://www.academicmultimediaservices.com/art/Docs.html > > Some of the bad doctors want to put women on Lupron before doing > surgery. Stay away from these. They feel Luporn helps control > bleeding. Lupron is a dangerous and very expensive drug, not > approved by the FDA for this use due to the dangers and the fact > that it worsens the outcome of surgery. It destroys the capsule > around fibroids so the doctor cannot tell the difference between > fibroid and uterine wall. It also results in a higher rate of > regrowth and complications in surgery, not to mention the damage > this drug does to your health. Some people have permanent severe > bone pain and health problems from this drug. > > For me, Myomectomy was my best choice. But, if you can hold out long > enough to get your thyroid dose up to 3 grains or more or wherever > it is best for you, I think your problem will deminish greatly. > Fibroids take about 3 years to shrink, but the symptoms should > dissapear when thyroid is optimized. > > I would have preferred to not have this major surgery and to have > had my hypothyroidism discovered. But, my surgery was very > successful and it took two years for just two small fibroids to > appear. I was hypo all this time and I know that is why two grew > again. The regrowth rate following a myomectomy is only 25% and 75% > of those never have any more problems after a good myomectomy. This > means that if the fibroids do regrow, they usually are not a problem. > > Tish > > Tish Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 20, 2005 Report Share Posted March 20, 2005 >The fibroids in the wall of the uterus are not >difficult to remove for the doctors with the proper skills. This seems to be a recurring theme - finding skilled physicians! Why is it SO hard to find a good one?? Laurie Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 20, 2005 Report Share Posted March 20, 2005 >The fibroids in the wall of the uterus are not >difficult to remove for the doctors with the proper skills. This seems to be a recurring theme - finding skilled physicians! Why is it SO hard to find a good one?? Laurie Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 20, 2005 Report Share Posted March 20, 2005 >The fibroids in the wall of the uterus are not >difficult to remove for the doctors with the proper skills. This seems to be a recurring theme - finding skilled physicians! Why is it SO hard to find a good one?? Laurie Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.