ESTROGEN REPLACEMENT DOES NOT POTENTIATE GONADOTROPIN-RELEASING-HORMONE AGONIST-INDUCED ANDROGEN SUPPRESSION IN TREATMENT OF HIRSUTISM

The therapies presently available for treating ovarian hirsutism are n ot uniformly effective, and therefore, much has been expected from GnR H agonists. These inhibit the secretion of gonadotropins and thereby s uppress ovarian function, but at the same time cause hypoestrogenic si de-effects. We, therefore, administered goserelin, a long-acting GnRH agonist, for treatment of 20 hirsute women (18 with polycystic ovaries ) for 9 months; half of them were randomized to receive cyclic estradi ol and medroxyprogesterone replacement from the fourth month onward. S eventeen patients completed the study. Goserelin suppressed ovarian fu nction, as evidenced by a profound reduc tion in serum estradiol level s. The circulating levels of total testosterone, free testosterone, an d androstenedione were lowered at 3 months by 29%, 31%, and 38%, respe ctively, but there was no effect on the levels of sex hormone-binding globulin (SHBG) or dehydroepiandrosterone sulfate. Ovarian suppression , maintained for the duration of the trial, alleviated hirsutism, as e videnced by a decrease in Ferriman-Gallwey hirsutism scores. Estrogen plus progestin replacement restored estradiol levels and increased SHB G levels, but did not potentiate the therapeutic effect of goserelin o r reduce free testosterone levels. Replacement therapy abolished or al leviated hypoestrogenic vasomotor symptoms, but it also caused bleedin g and premenstrual symptoms, which necessitated the withdrawal of 3 of 10 women from the treatment. Thus, goserelin is an effective treatmen t for ovarian hyperandrogenism. Simultaneous estrogen replacement abol ishes the hypoestrogenic side-effects, but does not potentiate the eff ect of goserelin on hirsutism. Interestingly, the estrogen-induced inc rease in SHBG did not affect free testosterone. Thus, the suppression of gonadotropins, rather than the increase in SHBG, appears to be of p rimary significance in the alleviation of ovarian hyperandrogenism by estrogens.