Azziz R, Ochoa T M, Bradley E L, Potter H D, Boots L R
Department of Obstetrics and Gynecology, University of Alabama, Birmingham 35233-7333, USA.
J Clin Endocrinol Metab. 1995 Dec;80(12):3406-11. doi: 10.1210/jcem.80.12.8530573.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
长效促性腺激素释放激素类似物(GnRH-a)的应用可使高雄激素血症女性的促性腺激素和雄激素水平受到抑制。然而,目前尚无随机研究比较GnRH-a与现有的多毛症治疗方法。我们推测,与口服避孕药(OCP)相比,GnRH-a治疗实现的更大程度的雄激素抑制可能会使多毛症改善得更快。为验证这一假设,我们对17名多毛症女性在随机接受以下两种治疗的6个月期间及之前进行了研究:1)亮丙瑞林长效制剂(3.75 mg/月)加结合雌激素(0.625 mg/天)和醋酸甲羟孕酮(10 mg;第1 - 12天;n = 9;亮丙瑞林+雌激素替代疗法[ERT]),或2)含双醋炔诺醇(1 mg)和炔雌醇(35 μg)的OCP(n = 8)。在第0、2、4、8、12和28周测量促黄体生成素(LH)、促卵泡生成素(FSH)、雌二醇、硫酸脱氢表雄酮、雄烯二酮(A4)、性类固醇结合球蛋白以及总睾酮和游离睾酮(T)。在治疗的第0周和第28周,通过患者自我评估和Ferriman-Gallwey评分主观评估多毛症情况,并通过测定面部毛发密度、毛发外径和生长速率进行客观评估,这些测定通过拍照和拔取毛发进行。在亮丙瑞林+ERT组而非OCP组中,循环LH和FSH水平显著降低。两组中,T和A4随治疗降低,尽管在接受OCP治疗的女性中A4水平的降低未达到显著水平。两个治疗组中循环性类固醇结合球蛋白水平均升高,但接受OCP治疗的女性变化更大。因此,尽管两个治疗组中计算得出的游离T百分比均显著降低,但接受OCP治疗的女性降低幅度更大。两种治疗方法均未使硫酸脱氢表雄酮水平发生变化。亮丙瑞林+ERT组患者的Ferriman-Gallwey评分有显著百分比降低,而OCP组未出现,通过自我评估,亮丙瑞林+ERT组分别有7名(78%)和5名(55%)患者,相比之下接受OCP治疗的女性分别有2名(25%)和2名(25%)注意到毛发的生长和质地有所改善。两种治疗方法在平均面部毛发密度或毛发外径方面均未观察到显著差异。采用拍照方法时,接受亮丙瑞林+ERT治疗的患者实际毛发生长速率降低,采用拔取毛发方法时,生长速率降低百分比。总之,与标准OCP方案相比,亮丙瑞林加周期性雌激素/孕激素治疗似乎能使多毛症改善得更快,且可能改善程度更大。(摘要截选至250词)