Differential suppression of testosterone and estradiol in hirsute women with the superactive gonadotropin-releasing hormone agonist leuprolide.

To determine the dose of the GnRH agonist leuprolide necessary to maximally suppress ovarian testosterone secretion, 10 moderately to severely hirsute women (5 with idiopathic hirsutism and 5 with polycystic ovarian syndrome) were given gradually increasing leuprolide doses, starting with either 5 or 10 micrograms/kg.day. Serum testosterone and estradiol, basal LH, and the LH response to GnRH were measured before and at the end of each treatment period, until maximal suppression of estradiol and testosterone occurred. Leuprolide was then continued for a total of 6 months to assess its clinical efficacy. Hirsutism scores and hair growth rates were determined before and after therapy. Serum estradiol and the LH response to GnRH were maximally or near-maximally suppressed in all women by the lowest doses of leuprolide used. Basal serum LH was not maximally suppressed in all women until a dose of 15 micrograms/kg.day was reached, and maximal testosterone suppression required 15 micrograms/kg.day or more in 7 of the 10 women. The addition of 0.5 mg dexamethasone daily for 4 weeks at the end of the study in 5 of the women reduced serum testosterone to undetectable levels. Symptomatic improvement in hirsutism occurred in 9 women, hirsutism scores decreased by at least 3 points in 5 women, and hair growth rates decreased in 8 women. These data indicate that low doses of leuprolide were sufficient to maximally suppress serum estradiol and the LH response to exogenous GnRH. Higher leuprolide doses were needed to maximally suppress serum testosterone and the basal LH levels. Leuprolide (20 micrograms/kg.day) effectively reduced hair growth in the majority of these women.