Couzinet B, Pholsena M, Young J, Schaison G
Service d'Endocrinologie et des maladies de la Reproduction, Hospital Bicêtre, Kremlin, France.
Clin Endocrinol (Oxf). 1993 Aug;39(2):157-62. doi: 10.1111/j.1365-2265.1993.tb01768.x.
We assessed in women the effects of androgen suppression on gonadotrophin secretion and the therapeutic efficacy of the pure anti-androgen flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide).
Ten women, aged 28-35 years, using an intrauterine device for contraception, were selected for this study. All women had idiopathic hirsutism with or without acne and seborrhoea. Flutamide was administered orally in a dose of 250 mg twice daily for 1 year. Basal body temperature was recorded and pelvic ultrasonography performed before and every 3 months during treatment. LH pulse frequency and amplitude (Cluster analysis) and basal and GnRH-stimulated plasma LH and FSH levels were determined on day 5 of the cycle prior to flutamide treatment, and after 6 and 12 months of therapy. Plasma total testosterone (T), non-SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3 alpha-diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle. Plasma oestradiol and progesterone levels were determined on day 22 of the studied cycles.
Disappearance of acne and seborrhoea occurred after 2 months with a marked improvement of hirsutism at 6 months. At 12 months, hirsutism had disappeared with a Ferriman and Gallwey score < 7. No adverse side-effects, apart from transient diarrhoea in two patients, were reported with this flutamide dose. None of the patients had any disturbance of menstrual cycles which remained ovulatory. The pure anti-androgen flutamide induced no significant change in LH pulsatile profile, nor in LH and FSH responsiveness to GnRH. Plasma concentrations of steroids were not altered. Plasma SHBG and 3 alpha-diol G levels did not change during flutamide treatment.
Flutamide, which interacts only with the androgen receptor, is effective for hirsutism, acne and seborrhoea, and does not disturb menstrual cyclicity or ovulation. It may represent a treatment of choice for essential hirsutism in women using safe contraceptive methods.
我们评估了雄激素抑制对女性促性腺激素分泌的影响以及纯抗雄激素药物氟他胺（2-甲基-N-[4-硝基-3-(三氟甲基)苯基]丙酰胺）的治疗效果。
本研究选取了10名年龄在28至35岁、使用宫内节育器避孕的女性。所有女性均患有特发性多毛症，伴有或不伴有痤疮和脂溢性皮炎。氟他胺口服给药，剂量为每日2次，每次250 mg，持续1年。在治疗前及治疗期间每3个月记录基础体温并进行盆腔超声检查。在氟他胺治疗前的周期第5天以及治疗6个月和12个月后，测定LH脉冲频率和幅度（聚类分析）以及基础和GnRH刺激后的血浆LH和FSH水平。在治疗前及治疗期间每3个月的周期第5天，测量血浆总睾酮（T）、非SHBG结合的T、雄烯二酮（A）、硫酸脱氢表雄酮（DHEAS）、雄烷二醇葡萄糖醛酸苷（3α-二醇G）和性激素结合球蛋白（SHBG）水平。在研究周期的第22天测定血浆雌二醇和孕酮水平。
2个月后痤疮和脂溢性皮炎消失，6个月时多毛症明显改善。12个月时，多毛症消失，Ferriman和Gallwey评分<7。除两名患者出现短暂腹泻外，该氟他胺剂量未报告其他不良副作用。所有患者的月经周期均无紊乱，仍有排卵。纯抗雄激素药物氟他胺未引起LH脉冲特征以及LH和FSH对GnRH反应性的显著变化。类固醇的血浆浓度未改变。氟他胺治疗期间血浆SHBG和3α-二醇G水平未变化。
仅与雄激素受体相互作用的氟他胺对多毛症、痤疮和脂溢性皮炎有效，且不干扰月经周期或排卵。对于采用安全避孕方法的女性特发性多毛症，它可能是一种首选治疗方法。
