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 not uniformly effective, and therefore, much has been expected from GnRH agonists. These inhibit the secretion of gonadotropins and thereby suppress ovarian function, but at the same time cause hypoestrogenic side-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 estradiol and medroxyprogesterone replacement from the fourth month onward. Seventeen patients completed the study. Goserelin suppressed ovarian function, as evidenced by a profound reduction in serum estradiol levels. The circulating levels of total testosterone, free testosterone, and androstenedione were lowered at 3 months by 29%, 31%, and 38%, respectively, 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 evidenced by a decrease in Ferriman-Gallwey hirsutism scores. Estrogen plus progestin replacement restored estradiol levels and increased SHBG levels, but did not potentiate the therapeutic effect of goserelin or reduce free testosterone levels. Replacement therapy abolished or alleviated hypoestrogenic vasomotor symptoms, but it also caused bleeding and premenstrual symptoms, which necessitated the withdrawal of 3 of 10 women from the treatment. Thus, goserelin is an effective treatment for ovarian hyperandrogenism. Simultaneous estrogen replacement abolishes the hypoestrogenic side-effects, but does not potentiate the effect of goserelin on hirsutism. Interestingly, the estrogen-induced increase in SHBG did not affect free testosterone. Thus, the suppression of gonadotropins, rather than the increase in SHBG, appears to be of primary significance in the alleviation of ovarian hyperandrogenism by estrogens.
Tiitinen
A
A
Department I of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Simberg
N
N
Stenman
U H
UH
Ylikorkala
O
O
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D005260:Female; D017273:Goserelin / Q000627:therapeutic use*; D006628:Hirsutism / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000627:therapeutic use*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000728:Androgens; D012738:Sex Hormone-Binding Globulin; D017273:Goserelin; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D017258:Medroxyprogesterone Acetate