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How Clomid Works
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.
Clomiphene citrate appears to act on the hypothalamus and is useful for women who do not ovulate because of hypothalamic or pituitary problems. Given early in the menstrual cycle (day three to seven), it suppresses the amount of naturally circulating estrogen. This "tricks" the pituitary into producing more follicular stimulating hormone (FSH) and luteinizing hormone (LH). These hormones then stimulate the ovary to ripen a follicle and release an egg. Of patients who are properly screened for use of this drug, about 70 percent will ovulate, and 40 percent of those will become pregnant. If a patient ovulates but does not become pregnant, the physician should check cervical factors. The anti-estrogenic effect of clomiphene citrate can create a "hostile" environment for conception.
Clomiphene works by 'kick-starting' the hormone system into stimulating an egg to grow. Normally the egg is released around mid-cycle (day 14), the time when you are most likely to conceive. It is probably best to make love every other day from about day 11-15 of your cycle, but this regime is not rigid and to be relaxed about it is certainly important.
The drug's similarity to oestrogen explains it ability to induce ovulation. It binds to oestrogen receptors in the hypothalamus, exerting only a weak biologic effect itself. This binding, however, limits the binding of endogenous oestrogen to these receptors, reducing negative feedback and leading to increased GnRH output. This leads to increased levels of FSH and LH, thus oestradiol and the normal events leading to ovulation. Clomiphene binding to the hypothalamic receptor lasts for weeks rather than hours. The effect of the drug on the hypothalamic-pituitary-ovarian axis is brief, however the drug remains in the circulation for longer periods. Only 50% of the dose is excreted after 5 days, and radiolabelled clomiphene has been demonstrated in the faeces up to 6 weeks after administration.
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