The administration of long-acting GnRH analogs (GnRH-a) results in gonadotropin and androgen suppression in hyperandrogenic women. Nonetheless, no randomized studies are available comparing GnRH-a with currently used treatments for hirsutism. We have hypothesized that the greater degrees of androgen suppression achieved with GnRH-a therapy could result in a more rapid improvement in hirsutism compared to oral contraceptive (OCP) administration. To test this hypothesis, we studied 17 hirsute women before and during 6 months of randomized treatment with 1) leuprolide depot (3.75 mg/month) plus conjugated estrogen (0.625 mg/day) and medroxyprogesterone acetate (10 mg; days 1-12; n = 9; leuprolide+ERT), or 2) an OCP containing ethynodiol diacetate (1 mg) and ethinyl estradiol (35 micrograms; n = 8). LH, FSH, estradiol, dehydroepiandrosterone sulfate, androstenedione (A4), sex steroid-binding globulin, and total and free testosterone (T) were measured at weeks 0, 2, 4, 8, 12, and 28. At 0 and 28 weeks of treatment, hirsutism was evaluated subjectively by patient self-evaluation and by the Ferriman-Gallwey score, and objectively by determination of facial hair density, outer hair shaft diameter, and growth rate, determined both photographically and in plucked hairs. In the leuprolide+ERT, but not OCP, groups, there was a significant decrease in the circulating LH and FSH levels. In both groups, T and A4 decreased with treatment, although the decrease in A4 levels did not reach significance in OCP-treated women. The circulating sex steroid-binding globulin level increased in both treatment groups, but the changes in the OCP-treated women was greater. Consequently, although the calculated percent free T decreased significantly in both treatment groups, the decrease was greater in the OCP-treated women. The dehydroepiandrosterone sulfate level did not change with either therapy. A significant percent decrease in the Ferriman-Gallwey score was noted in the leuprolide+ERT, but not OCP, patients, and by self-evaluation, seven (78%) and five (55%) of leuprolide+ERT patients, compared to two (25%) and two (25%) OCP-treated women, noted an improvement in hair growth and texture, respectively. No significant difference in mean facial hair density or outer hair diameter was noted with either therapy. Patients treated with leuprolide+ERT demonstrated a decrease in the actual hair growth rate, using the photographic method, or percent decrease in growth rate, using plucked hair. In conclusion, treatment with leuprolide plus cyclic estrogen/progestin appears to provide a more rapid, and possibly greater, improvement in hirsutism, compared to a standard OCP regimen. © 1995 by The Endocrine Society.