COMPARISON OF A GONADOTROPIN-RELEASING-HORMONE AGONIST AND A LOW-DOSE ORAL-CONTRACEPTIVE GIVEN ALONE OR TOGETHER IN THE TREATMENT OF HIRSUTISM

被引:46
作者
HEINER, JS
GREENDALE, GA
KAWAKAMI, AK
LAPOLT, PS
FISHER, M
YOUNG, D
JUDD, HL
机构
[1] UNIV CALIF LOS ANGELES, DEPT OBSTET & GYNECOL, LOS ANGELES, CA 90024 USA
[2] UNIV CALIF LOS ANGELES, DEPT INTERNAL MED, LOS ANGELES, CA 90024 USA
[3] UNIV CALIF LOS ANGELES, DEPT ANAT, LOS ANGELES, CA 90024 USA
[4] SYNTEX LABS INC, PALO ALTO, CA 94303 USA
关键词
D O I
10.1210/jc.80.12.3412
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Chronic GnRH agonist therapy lowers androgens and decreases androgen-dependent hair shaft diameter, but the resulting induction of hypoestrogenemia has limited its usefulness as a single agent. Estrogen- and progestin-containing oral contraceptives also reduce circulating androgen levels and are commonly used empirically for the treatment of hirsutism, but have not been evaluated in a blinded randomized controlled fashion. The present study is the first double masked trial to evaluate the combination use of a GnRH agonist and an estrogen-containing oral contraceptive and tests our hypothesis that these could synergistically reduce androgen levels and suppress hormone-dependent hair growth while avoiding the symptoms and risks of agonist-induced hypoestrogenemia. We enrolled 64 women in a 24-week blinded randomized controlled trial to compare placebo, nafarelin (NAF; 400 mu g, intranasal spray, twice daily), norethindrone (1 mg), and ethinyl estradiol (NOR 1/35; 0.035 mg, daily, for 3 of 4 weeks), or combined use of NAF and NOR 1/35 for 24 weeks. At baseline and every 8 weeks, we measured gonadotropins, estrogens, androgens, and hair growth. Bone density was assessed by dual energy x-ray adsorptiometry, and hot flashes were measured objectively. Baseline total testosterone (T), free T, percent free T, and sex hormone-binding globulin-binding capacity were similar among groups. With treatment, significant reductions (P = 0.01) in total T were seen with combination and NAF only therapy. Significant increases (P < 0.001) in the sex hormone-binding globulin-binding capacity were seen in women given NOR 1/35 alone or in combination with NAF. Free T levels decreased to approximately half of baseline levels with combination treatment (17.9 to 6.4 nmol/L; P < 0.001) and NOR 1/35 alone (20.8 to 10.2 nmol/L; P < 0.001). There was a significant decrease in hair shaft diameter after combination therapy (P < 0.05) that was not seen with either agent alone. Combination therapy also prevented the hot flashes and bone loss that occurred with agonist alone. In summary, our results demonstrate that combination GnRH agonist and low dose oral contraceptive therapy is more effective than either agent alone in the treatment of hirsutism and avoids the hypoestrogenic complications that occur with agonist only therapy.
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收藏
页码:3412 / 3418
页数:7
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