Linking Estrogen Deficiency to Autoimmune Diseases

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Linking 'Estrogen Deficiency' to Autoimmune Diseases like MS, RA,

SLE, & IBD

Autoimmune disorders are diseases in which the body's own immune

system develops antibodies for, and attacks self tissue. This may

often lead to dysfunction, and eventual loss of function of the

targeted tissues and organ systems. Most autoimmune disorders are

influenced by environmental conditions, but many still have a

significant genetic relation.

No single genetic defect has yet been established for autoimmune

disorders, including: rheumatoid arthritis (RA), multiple sclerosis

(MS), systemic lupus erythematosus (SLE), and diabetes type 1. These

disorders are considered " polygenic " or to be determined by more

than one gene.

It is understood that the estrogens have some effect in modulating

or affecting change in autoimmune diseases. This link has been

especially strong with estradiol, but other estrogens as well.

Estrogen almost certainly plays a role in influencing autoimmune

diseases such as MS. This is suspected to be the case in other

autoimmune disorders too: as seen in patients with RA and SLE.

It is proposed that not only estradiol has interactions with the

immune system, but also estradiol precursor hormones and

intermediate metabolites, such as DHEA, may play a role.

Due to the sheer volume of hormones and interleukins and related

metabolites involved with the immune cascade, it is often difficult

to see the effect that one hormone has.

The association between estrogens and the immune system may be

linked back to pregnancy. Changes in the immune system are necessary

during pregnancy to prevent rejection of the fetus. Estrogen also

has a key role in various physiological systems of the body besides

reproduction. This has been proposed to be the reason behind the

bias seen between men and women for different immunological

disorders.

Many inflammatory diseases, such as RA and MS are ameliorated or

improve during pregnancy but worsen after childbirth[1,2].

Pregnancy appears to have a significant protective effect on women

with MS.

The number of MS attacks or relapses is reduced during pregnancy,

especially in the second and third trimesters. It is proposed that

this effect is due to the increased estriol (E3) levels caused by

pregnancy.

Estriol is a protective estrogen with weak estrogenic properties. It

binds to estrogen receptor sites to prevent estradiol binding. The

PRIMS study[3] suggests that treatment with Estriol in a dosage of

approximately 8mg/day, about the same as that seen in the 3rd

trimester of pregnancy, is protective of MS.

Estriol given to nonpregnant women with relapsing-remitting MS

showed increased protective immune responses, decreased number and

volume of lesions seen on monthly cerebral MRIs, and fewer number of

relapses[3].

Systemic lupus erythematosus has been reported to be either

unaffected by pregnancy[4] or aggravated[5]. While both RA and MS

are impacted by the immune system in different ways, pregnancy also

seems to affect these disorders differently.

It seems that it is estrogen, not progesterone that may confer

protection against RA.

The flare-up of arthritis after childbirth is believed to be caused

by the increased levels in prolactin due to lactation.

Disease outbreak after birth may be prevented by estradiol

administered immediately after birth. Since estrogen levels drop

just prior to birth, there is increased chance for a prolactin

stimulated immune response, due to estrogen no longer being

available in sufficient quantities to suppress this reaction.

Fluctuations in disease symptoms in RA, MS and SLE are reported to

correlate with the menstrual cycle. In RA, several studies on

estrogen replacement therapy have shown an improvement in the

disease in postmenopausal women[7,8].

Men with RA typically show low testosterone levels.

This link suggests that testosterone plays a role. Indeed,

testosterone replacement has been implicated to have beneficial

effects[9].

Testosterone is regarded as an immunosuppressive hormone and a lack

of testosterone produces a loss of protection against development of

RA.

Estrogen is noted to have many varying effects on immune cells.

Treatment has been shown to impact development and differentiation

of some immune cells and suppress immune functions of others[10, 11,

12].

Experimental evidence shows that estrogen may possess strong anti-

inflammatory properties. Kane, et.al.[13] put this to test.

In their study of 65 menopausal women with inflammatory bowel

disease (IBD), it was found that HRT caused ''significantly less''

disease flares. The effect seen strengthened when the women took HRT

for at least one year.

Fibromyalgia is another autoimmune disease that may be hormonally

modulated. A search of the data linking fibromyalgia to estrogen

levels showed that there is no link[14,15]. This was conclusively

found in two large randomized controlled trials, implying that the

data for this is robust. The trials do however prove that

fibromyalgia is associated with lower levels of cortisol.

Maintaining estradiol and other hormones within a normal therapeutic

range may improve the course of many coexisting conditions in

addition to providing relief of menopausal symptoms.

Bellevue Pharmacy Solutions has a staff of consultant pharmacists

ready to assist you and your physician with managing your compounded

bioidentical hormones replacement.

References:

1. Ostenson M, Aune B, Husby G. Effects of pregnancy and hormonal

changes on the activity of rheumatoid arthritis. Scand J Rheumatol

1983;12:69

2. Hutchinson M. Pregnancy in multiple sclerosis. J Neurol Neurosurg

Psychitry 1993;56:1043

3. Confavreux C, et.al. Rate of pregnancy-related relapse in

multiple sclerosis (PRIMS). NEJM 1998;339:285

4. Tincani A, et.al. Systemic lupus erythematosus in pregnancy.

Lancet 1991;338:756

5. Alekberova Z, Kosheleva N. Lupus and pregnancy in systemic lupus

erythematosus. Am J Reprod Immunol 1992;28:288

6. Mac AG, et.al. Effect of hormone replacemt therapy in

rheumatoid arthritis: A double blind placebo-controlled study. Ann

Rheum Dis 1994;53:54

7. Hall GM, et.al. A randomized controlled trial of the effect of

hormone replacement therapy on the disease activity in

postmenopausal rheumatoid arthritis. Ann Rheum Dis 1994;53:112

8. Cutolo M, et.al. Androgen replacement therapy in male patients

with rheumatoid arthritis. Arthritis Rheum 1991;34:1

9. Baranao RI, Tenenbaum A, Rumi LS. Effects of sexual steroid

hormones on the functionality of murine peritoneal macrophages.

Steroids 1991;56:481

10. fsson E, Tarkowski A, Carlsten H. Anti-inflammatory

properties of estrogen I. in vivo suppression of leukocyte

production in bone marrow and redistribution of peripheral blood

neutrophils. Cell Immunol 1992;142:67

11. Seaman WE, Gindhart TD. Effect of estrogen on natural killer

cells. Arthritis Rheum 1979;22:1234

12. Kane SV, Reddy D. Hormonal replacement after menopause is

protective of disease activity in women with inflammatory bowel

disease. Am J Gastroenterol 2005;100:S-288

13. Gur A, et.al. Hypothalamic-pituitary-gonadal axis and cortisol

in young women with primary fibromyalgia: the potential roles of

depression, fatigue, and sleep disturbance in the occurrence of

hypocortisolism. Ann Rheum Dis 2004;63:1504

14. Cevik R, et.al. Cortisol and hypothalamic-pituitary-gonadal axis

hormones in follicular-phase women with fibromyalgia and chronic

fatigue syndrome and effect on depressive symptoms on these

hormones. Arthritis Res Ther 2004;6:R232

source:

http://www.bpharmacysolutions.com/patient/articles/2006/1116-32.asp