CLOMID USE AND ABUSE

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Clomid Use and Abuse

Clomiphene Citrate (Clomid, Serophene)

Some women can't get pregnant because they don't secrete enough LH and FSH at

the right time during the cycle and, as a result, they don't ovulate. For these

women, the first drug doctors often prescribe is clomiphene citrate (Clomid,

Serophene). This synthetic drug stimulates the hypothalamus to release more

GnRH, which then prompts the pituitary to release more LH and FSH, and thus

increases the stimulation of the ovary to begin to produce a mature egg.

Clomiphene is a good first choice drug when a woman's ovaries are capable of

functioning normally and when her hypothalamus and pituitary are also capable of

producing their hormones. In short, the woman's reproductive engine is in

working order, but needs some revving up.

Structurally like estrogen, clomiphene binds to the sites in the brain where

estrogen normally attaches, called estrogen receptors. Once these receptor sites

are filled up with clomiphene, they can't bind with natural estrogen circulating

in the blood and they are fooled into thinking that the amount of estrogen in

the blood is too low. In response, the hypothalamus releases more GnRH, causing

the pituitary to pump out more FSH, which then causes a follicle to grow to

produce more estrogen and start maturing an egg to prepare for ovulation.

Typically, a woman taking clomiphene produces double or triple the amount of

estrogen in that cycle compared to pretreatment cycles

If a woman is menstruating, even if irregularly, clomiphene is usually

effective, particularly if she develops follicles that aren't reaching normal

size. Usually, a mature follicle is about 20 millimeters in diameter, or about

the size of a small grape, just before it ruptures and releases its egg.

Clomiphene may help small, immature follicles grow to maturity.

A low estradiol level in a woman's blood correlates with an inadequately

stimulated, small follicle. A woman having a spontaneous ovulation cycle (that

is, ovulating without the aid of fertility drugs) generally has peak estradiol

levels ranging from 100 to 300 picograms (one trillionth of a gram)/ml. A woman

may have enough hormones to produce an egg, but if her estradiol production by

the follicles is low (less than 100 pg/ml), she may not adequately stimulate her

cervix to produce fertile mucus or stimulate her endometrium to get ready to

accept a fertilized egg for implantation. Clomiphene could boost the weak

signals from the hypothalamus to the pituitary to the ovaries.

" A woman who ovulates infrequently, say at six-week intervals or less often, is

also a good candidate for clomiphene therapy, since clomiphene will induce

ovulation more frequently. The more a woman ovulates, the more opportunities her

mature eggs have to be exposed to her husband's sperm and, therefore, the

greater her chance to become pregnant.

Clomiphene is also often effective for a woman with luteal phase defect (LPD). A

woman with LPD may begin the ovulation process properly, but her ovarian

function becomes disrupted, resulting in low production of the hormone

progesterone in the luteal phase of the menstrual cycle. Following ovulation,

the ovary produces progesterone, the hormone needed to prepare the uterine

lining for implantation of the fertilized egg, which has divided and entered the

uterine cavity. A fall in progesterone levels in the blood during this critical

time can interfere with early embryo implantation or, even if a fertilized egg

has already implanted, cause a woman to menstruate too early and end a pregnancy

within a few days after implantation.

Using an LH-urine detector kit or keeping a basal body temperature (BBT) chart

can help a woman taking clomiphene determine whether the luteal phase of her

cycle is shorter than the normal fourteen days. The luteal phase of the cycle,

the length of time from ovulation until she menstruates, has a normal range of

thirteen to fifteen days. Clomiphene can often " tune up " the hypothalamus and

pituitary so they keep producing the hormones the ovary needs to manufacture

progesterone throughout the luteal phase.

" Of women whose only fertility problem is irregular or no ovulation at all,

about 80 percent will ovulate and about 50 percent will become pregnant within

six months of clomiphene treatments. About three percent of women on clomiphene

have a multiple pregnancy, usually twins, compared with about one percent in the

general population.

If a woman responds to clomiphene and develops a mature follicle (determined by

adequate estrogen production and ultrasound examination), but has no LH surge by

cycle day 15, then injection of the hormone human chorionic gonadotropin (HCG),

which actslike LH, can be given to stimulate final egg maturation and follicle

rupture, releasing the egg. The woman tends to ovulate about 36 hours after the

LH surge or HCG injection, which can be confirmed by further ultrasound scans.

" Clomiphene is a relatively inexpensive drug, and is taken orally for only five

days each month. The doctor attempts to initiate clomiphene therapy so that the

woman ovulates on or around day 14 of a regular 28-day cycle. The simplest, most

widely used dose starts with one daily 50 mg. tablet for five days starting on

cycle day three or five. If a woman ovulates at this dose, there is no advantage

to her increasing the dosage. In other words, more of the drug isn't necessarily

better. In fact, more may be worse, producing multiple ovulation, causing side

effects such as an ovarian cyst or hot flashes, and most commonly, interfering

with her fertile mucus production.

If a woman doesn't ovulate after taking one clomiphene tablet for five days,

then her doctor will usually double the daily dose to two tablets (100 mg) in

her next cycle, and if she still doesn't respond, then triple the daily dose to

150 mg, or add another fertility medication such as human menopausal

gonadotropin (Pergonal) in the next cycle. Some doctors increase the dose up to

250 mg. a day, but this is NOT recommended by either of the drug's two

manufacturers. Women tend to have side effects much more frequently at higher

doses.

If the dose of clomiphene is too high, the uterine lining may not respond

completely to estrogen and progesterone stimulation, and may not develop

properly. As a result, a woman's fertilized egg may not be able to implant in

her uterus.

Side Effects

Because Clomiphene binds to estrogen receptors, including the estrogen receptors

in the cervix, it can interfere with the ability of the cervical mucus glands to

be stimulated by estrogen to produce fertile mucus. Only " hostile " or dry

cervical mucus may develop in the days preceding ovulation. If this occurs,

adding a small amount of estrogen beginning on cycle day 10 and continuing until

the LH surge may enhance cervical mucus production.

Some women taking clomiphene experience hot flashes and premenstrual-type

symptoms, such as migraines and breast discomfort (particularly if they have

fibrocystic disease of the breasts). Visual symptoms such as spots, flashes or

blurry vision are less common and indicate that treatment should stop.

Clomiphene is a very safe medication with relatively few contraindications.

Preexisting liver disease is one contraindication since clomiphene is

metabolized by the liver. Enlarged ovaries are also a contraindication since

clomiphene may occasionally produce hyperstimulation of the ovaries.

The hot flashes are just like the hot flashes women experience at menopause when

the level of estrogen circulating in the blood is low. The clomiphene fools the

brain into thinking that blood estrogen levels are low.

Clomiphene Abuse

Too often, doctors give clomiphene to women with unexplained infertility before

the couple has a fertility workup, or even after they have a workup, but there

is no evidence of an ovulation disorder. This empiric therapy may create new

problems, such as interfering with fertile mucus production, and often delays

further evaluation that can lead to a specific diagnosis and proper treatment.

For a woman who has normal, spontaneous ovulation, driving the pituitary harder

with clomiphene won't make ovulation any more normal. If a woman has taken

clomiphene for several cycles without becoming pregnant, then she and her

fertility specialist should investigate other conditions that may be preventing

her pregnancy.

After noting a good postcoital test (PCT) during a fertility workup, some

doctors fail to repeat the test after placing a woman on clomiphene. A PCT needs

to be repeated to check the quality of the woman's cervical mucus while she is

on clomiphene, since 25 percent or more of women who take the drug develop

cervical mucus problems. It's important for a woman to monitor her cervical

mucus production during every cycle while trying to become pregnant, including

her cycles while taking clomiphene.

Taken from www.inciid.org

Hart

Baby Bean due 30 June 2002