USMLE CLOMIPHENE & PCOS

[lllTRAUMADOClll]

In PCOS there is an unregulated increase in LH, why is it Rx ed w/ clomiphene, a partial agonist of estrogen that causes increase in LH and FSH ?

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[Transposony]

PCOS is due to a very complex interplay of various hormones (Hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS). There is a complex positive feedback loop of insulin resistance and hyperandrogenism (Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese patients creates the paradox of having both excess androgens (which are responsible for hirsutism and virilization) and estrogens (which inhibits FSH via negative feedback).

However, it is mainly due to LH/FSH ratio imbalance. Due to feedback mechanism FSH is constantly being inhibited and LH release being stimulated.
Simply put, Clomifene (a SERM) increases FSH release thereby facilitating ovulation.