Treatment of Hirsutism with a Gonadotropin-Releasing Hormone Agonist (Nafarelin)∗

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Abstract
GnRH analogs inhibit the secretion of gonadotropins and, therefore, that of estrogens and androgens of ovarian origin. The purpose of this study was to investigate the use of one superactive agonistic GnRH analog, nafarelin, in the treatment of hirsutism. Six hirsute women were treated with nafarelin (1000 µg/day) for 6 months. An acute rise in serum gonadotropin levels occurred in response to nafarelin administration initially, but it lasted less than 2 weeks. Serum gonadotropin, testosterone, free testosterone, and androstenedione concentrationsdecreased significantly during treatment. Mean serum LH levels decreased from 17.9 ± 4.6 (±SE) to 5.0 ± 0.5 mlU/ml (P < 0.01), and FSH decreased from 9.3 ± 0.7 to 7.2 ± 0.9 mlU/ml (P < 0.05) after 1 month of treatment. The total testosterone concentration fell from 0.77 ± 0.10 to 0.40 ± 0.14 ng/ml (P < 0.01) after 1 month of therapy, and free testosterone decreased from 10.7 ± 2.7 to 4.1 ± 1.6 pg/ml (P < 0.01) after 3 months. Androstenedione levels decreased from 2.4 ± 0.4 to 1.2 ± 0.2 ng/ml (P < 0.01) after 1 month of treatment. The mean concentrations of all of the above hormones remained suppressed throughout treatment. Serum 5α-androstane-3α,17β-diol glucuronide levels did not decrease significantly during treatment, nor did dehydroepiandrosterone sulfate levels. The mean estradiol concentration during treatment was 34.8 ±3.1 pg/ml. The clinical response was very good; hair growth was slower, and new hair was less coarse compared to the pretreatment period. Hirsutism scores (determined by Ferriman-Gallwey assessment of extent and quality of body hair) improved in four of the six patients. In the six patients, the mean score decreased significantly from 19.3 ± 3.3 to 13.2 ± 2.8 (P < 0.05) at the end of treatment. These data demonstrate that by suppressing ovarian androgen production, nafarelin may be useful for the treatment of hirsutism associated with either increased ovarian androgen production or increased sensitivity of the hair follicle to normal concentrations of circulating androgens.