Moghetti P, Castello R, Negri C, Tosi F, Magnani C M, Fontanarosa M C, Armanini D, Muggeo M
Division of Metabolic Diseases, University of Verona, Italy.
Fertil Steril. 1995 Sep;64(3):511-7. doi: 10.1016/s0015-0282(16)57785-1.
To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women.
Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment.
Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug.
Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.
研究低剂量氟他胺治疗对多毛女性临床及激素参数以及雄激素受体状态的长期影响。
对18例月经规律的多毛患者进行基础研究，并在其接受125毫克氟他胺治疗期间进行研究，每日三次，共12个月。研究期间，有性生活的女性采用屏障避孕法或宫内节育器避孕。在整个研究过程中评估安全参数。采用改良的费里曼-盖尔维评分对多毛症进行分级，并在基础状态及治疗期间每4个月评估一次激素参数。在治疗3至4个月前后进行促性腺激素释放激素和促肾上腺皮质激素刺激试验。此外，在月经周期的卵泡期和黄体期，分别于基础状态及氟他胺治疗4个月后，测定单核白细胞中雄激素受体的浓度。
所有女性对氟他胺耐受性良好，仅有1例患者在治疗8个月后出现血清转氨酶升高。治疗期间所有女性的多毛症均明显改善（1年后费里曼-盖尔维评分：4.1±0.5，而治疗前为14.1±0.9）。血清雄激素水平降低，而基础状态或促性腺激素释放激素刺激后的促性腺激素、皮质醇以及促肾上腺皮质激素刺激后的17α-羟孕酮反应均未观察到变化。月经周期仍为排卵型。治疗前，黄体期的雄激素受体数量高于卵泡期。给予抗雄激素药物后，这种节律性差异消失。
氟他胺治疗多毛症有效，但需要持续监测肝功能。血清雄激素水平降低可能会增强雄激素受体阻断作用。氟他胺会影响月经周期中的雄激素受体行为。这一发现的意义尚待阐明。
