Low Dose Flutamide in the Treatment of Acne Vulgaris in Women with or without Oligomenorrhea or Amenorrhea

　　　　　背景：皮膚中，雄性素之活性表現取決於睪固酮被「5α還原酵素」還原為二氫睪 固酮之多寡。罹患痤瘡之婦女，常有這種周邊代謝過盛之情形。本研究之目的，在評估低劑 量flutamide且合併或不合併有「順序性雌激素─黃體素」之治療對痤瘡的療效，及對血中 雄性素之影響。 方法：本研究囊括42位罹患痤瘡且合併有寡月經或無月經之婦女(第一組)、及10位罹 患痤瘡但有正常月經周期之婦女(第2組)、及15位寡月經但無罹患痤瘡之婦女(第3組，對 照組)。第1組之婦女，月經第5天至第25天給予flutamide (250 mg/日)及合併「順序性雌 激素─黃體素」之治療。第2組之婦女，只給21天之flutamide (250mg/日，月經第5天至 第25天)。第3組之婦女，只給21天「順序性雌激素─黃體素」之治療(月經第5天至第25 天)。 結果：第1組與第2組之婦女，治療3至6個月後，痤瘡之數目與嚴重程度都大為改善， 且其痤瘡之數目與嚴重程度，於停藥6個月後，仍較未治療前輕微。第1組之婦女未經治療 前，其血中之雄性素，如：睪固酮(T)、androstenedione (A)、dehydroepiandrosterone sulfate (DHEA-S)及游離雄性素指數(FAI)等都偏高；經治療後，這些雄性素及FAI都下降；但性激 素結合球蛋白(SHBG)反而上升。第2組之婦女經治療後，痤瘡之數目與嚴重程度都獲得改 善，但血中之雄性素值，包括T、A及DHEA-S，均無明顯之變化。第3組之婦女經治療後， 其血中之雄性素，亦無明顯之變化。 結論：低劑量flutamide (250 mg/日)，合併或不合併使用「順序性雌激素──黃體素」， 對罹患痤瘡且合併或不合併有寡月經或無月經之婦女，有明確之療效。而flutamide的抗雄 性素作用，雖然對臨床症狀之改善明顯，但對血中雄性素之濃度卻不一定有影響。
　　　　　Background: In the skin, the expression of androgen action is dependent on the reduction of testosterone to dihydrotestosterone mediated by the enzyme 5γ-reductase. Additionally, an exaggeration of this peripheral metabolism has been associated with acne in women. Methods: Fifty-two women with acne vulgaris but without hirsutism were recruited in this study, including 42 with oligomenorrhea or amenorrhea (Group 1) and 10 with regular menstrual cycles (Group 2). As a control, another 15 oligomenorrheic women without acne were also studied (Group 3). Flutamide combined with sequential estrogen-progestogen preparations was given to patients in Group 1. In Group 2, flutamide alone was administered. In Group 3, the women were treated with sequential estrogenprogestogen. Results: In Groups 1 and 2, a significant decrease in the number of inflammatory lesions was found at the end of 3 and 6 months of treatment, and even after discontinuation of therapy for 6 months. Before treatment, patients in Group 1 showed signs of biochemical hyperandrogenism, including elevated levels of serum testosterone (T), androstenedione (A), and dehydroepiandrosterone sulfate (DHEA-S)，as well as a decreased level of sex hormone-binding globulin (SHBG). A decrease in circulating T and A, and an elevation in serum SHBG were found 3 and 6 months after treatment in Group 1. In Group 2, clinical improvement of acne was achieved by flutamide alone without alteration in circulating androgens (including T, A, and DHEA-S). Similarly, no change in serum androgens was observed in the women of Group 3 after treatment. Conclusion: A low dose of flutamide (250 mg/day) in association with or without estrogen- progestogen is effective for the clinical improvement of acne vulgaris in women with or without oligomenorrhea or amenorrhea. However, the effectiveness on hyperandrogenic symptoms by antiandrogens may or may not be reflected by the suppression of serum androgens.