Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study.

ABSTRACT

The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and a combination of OCPs and GnRH-a in the treatment of hirsute women was compared and the impact of these treatments on hormonal and Ca metabolism was investigated. Thirty-three women were prospectively enrolled and randomized into three treatment groups (11 in each group). The serum levels of LH, estradiol, testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone declined in all 3 treatment groups, whereas the inclusion of GnRH-a treatment tended to promote a more rapid decrease in these hormone levels. Total cholesterol, low density lipoprotein, and high density lipoprotein levels remained unchanged. The assessment of hirsutism by the Ferriman-Gallwey score revealed a similar 25% reduction in score by all three treatment groups by 6 months. In addition, no difference was detected between groups with respect to hair diameters and the vellus index. Clinical assessment of hirsutism at 3 months by the patients revealed that the GnRH-a and the OCPs-plus-GnRH-a groups had better responses than the group on OCPs alone, but by 6 months all three groups were similar. The symptoms of hot flashes and vaginal dryness were greatest in subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased significantly in subjects treated with the GnRH-a alone, whereas a decrement or no changes occurred for these measurement in the other two groups. The estimated Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups but declined by 90 mg/day from baseline in the GnRH-a-treated women (p < or = 0.001). Bone density significantly decreased in the lumber spine in women treated with GnRH-a alone, with a less marked decline in the femoral neck. In contrast, women receiving OCPs plus GnRH had increased bone density in the lumbar spine. It is concluded that 1) clinical measures of hirsutism are not different after 6 months of treatment with OCPs alone, GnRH-a alone, or a combination of the two; 2) the decline in gonadotropins and steroid hormones and improvement in clinical response were more rapid and pronounced when GnRH-a treatment was added to OCP administration; and 3) the negative impact of GnRH-a alone on Ca balance and bone loss limits its usefulness as a single agent for long-term therapy of hirsutism.

ABSTRACT

PIP The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and a combination of OCPs and GnRH-a in the treatment of hirsute women (modified Ferriman-Gallwey score 10), 20-39 years old, was compared and the impact of these treatments on hormonal and Ca metabolism was investigated. 33 women were prospectively enrolled and randomized into 3 treatment groups (11 in each group) 1) OCPs [35 mcg ethinyl estradiol plus 1 mg norethindrone administered cyclically]; 2) GnRH-a, 3.75 mg im, every 4 weeks for 24 weeks; or 3) a combination of both OCPs and GnRH-a at the above doses taken concurrently. All medications were administered for 6 months. The serum levels of LH, estradiol, testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone declined in all 3 treatment groups. The assessment of hirsutism by the Ferriman-Gallwey score revealed a similar 25% reduction in score by all 3 treatment groups by 6 months. The symptoms of hot flashes and vaginal dryness were greatest in subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased significantly in subjects treated with the GnRH-a alone. In the OCP groups there was significant decline in serum Ca from baseline to 24 weeks (p or = 0.01). There was significant urinary loss of Ca in the GnRH-a group with respect to 24-hour excretion (p or = 0.001). The estimated Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups, however, it declined by 90 mg/day from baseline in the GnRH-a-treated women from 111 +or- 43 to 21 +or- 58 mg/day (p or = 0.001). Bone density significantly decreased (by 2.7%) in the lumber spine in women treated with GnRH-a alone (p or = 0.02), with a less marked decline in the femoral neck. The negative impact of GnRH-a alone on Ca balance and bone loss limits its usefulness as a single agent for long-term therapy of hirsutism.