PHYSIOLOGICAL ESTROGEN REPLACEMENT MAY ENHANCE THE EFFECTIVENESS OF THE GONADOTROPIN-RELEASING-HORMONE AGONIST IN THE TREATMENT OF HIRSUTISM

GnRH agonists (GnRH-A) have been used for the treatment of hirsutism i n women with ovarian hyperandrogenism. However, significant side-effec ts, including vasomotor symptoms and bone loss, have prevented the lon g term use of this therapy. In this study, we evaluated the effects of low dose (physiological) estrogen replacement on the side-effects and clinical and hormonal parameters of 22 hirsute women with ovarian hyp erandrogenism when treated with a long-acting GnRH-A, Decapeptyl. Ten patients with Ferriman-Gallwey (FG) scores averaging 13.4 +/- 1.5 were randomly assigned to be treated with Decapeptyl alone (3.75 mg, im, e very 28 days for 6 months), and 12 other patients with FG scores avera ging 13.3 +/- 1 received Decapeptyl with estrogen (conjugated equine e strogens, 0.625 mg) for 21 days and medroxyprogesterone acetate (10 mg ) for 10 days (days 12-21). After 6 months, LH was suppressed in both groups, whereas FSH was significantly reduced only in the group receiv ing GnRH-A with estrogen (2.5 +/- 4 vs. 4.8 +/- 0.6 IU/L; P < 0.01). S erum androgen levels were reduced in both groups, although the reducti on of testosterone and unbound testosterone was greater in the group r eceiving hormonal replacement [1.73 +/- 0.3 vs. 2.57 +/- 0.4 nmol/L fo r testosterone (P < 0.05); 8.3 +/- 1 vs. 14.6 +/- 2.8 pmol/L for unbou nd testosterone (P < 0.05)]. The reduction in hirsutism scores was gre ater with hormonal replacement (FG scores, -4.1 +/- 0.3 vs. -2.5 +/- 0 .3; P < 0.05), whereas the polycystic appearance of ovaries by ultraso und was decreased in both groups. Amenorrhea and vasomotor symptoms we re observed only with GnRH-A alone. Serum osteocalcin rose significant ly with GnRH-A alone, reflecting a change in bone turnover (0.49 +/- 0 .05 to 0.64 +/- 0.09 nmol/L; P < 0.05), but was unchanged with hormona l replacement. Patients receiving hormonal replacement had treatment e xtended to 1 yr. A further improvement of hirsutism, with scores dropp ing into the normal range (4.9 +/- 0.7), as well as a normalization of ovarian morphology were evident at this time. In conclusion, low dose (physiological) estrogen replacement may enhance the effects of GnRH- A treatment, while preventing most of the side-effects encountered wit h GnRH-A alone. This may allow more prolonged treatment, which is nece ssary for hirsutism.