Karrer-Voegeli Sandra, Rey François, Reymond Marianne J, Meuwly Jean-Yves, Gaillard Rolf C, Gomez Fulgencio
From the Service of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine (SKV, FR, MJR, RCG, and FG) and Service of Radiodiagnostic and Interventional Radiology (JYM), University Hospital, Lausanne, Switzerland.
Medicine (Baltimore). 2009 Jan;88(1):32-45. doi: 10.1097/md.0b013e3181946a2c.
Hirsutism, acne, alopecia, and oligo-amenorrhea are clinical expressions of hyperandrogenism, one of the most frequent endocrine disorders in women of reproductive age. Women referred to our endocrine clinics for skin symptoms of hyperandrogenism underwent a laboratory workup to evaluate hormone measurements and received antiandrogen therapy. We retrospectively analyzed the outcome of 228 consecutive patients investigated over 6 years.Patients with hirsutism had higher levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), and salivary testosterone; lower levels of sex hormone-binding globulin (SHBG); and a higher prevalence of oligo-amenorrhea than patients with alopecia, while patients with acne showed intermediate values. Hirsutism score correlated positively with androstenedione, DHEAS, and salivary testosterone, and correlated negatively with SHBG; salivary testosterone showed the highest correlation coefficient. Total testosterone was not significantly different among patients with hirsutism, alopecia, or acne, and did not significantly correlate with hirsutism score. Hirsutism and oligo-amenorrhea were the most sensitive symptoms of hyperandrogenism, and no androgenic parameter alone allowed us to identify all cases of hyperandrogenism.Patients of central European origin sought consultation with milder hirsutism scores than patients of southern European origin. There was, however, no difference in the clinical-biological correlation between these groups, arguing against differences in skin sensitivity to androgens.Polycystic ovary syndrome, defined as hyperandrogenism (hirsutism or elevated androgens) and oligo-amenorrhea, was diagnosed in 63 patients (27.6%), an underestimate compared with other reports that include systematic ovarian ultrasound studies. Neither pelvic ultrasound, used in a limited number of cases, nor the luteinizing hormone/follicle-stimulating hormone ratio helped to distinguish patients with polycystic ovary syndrome from the other diagnostic groups. These included hyperandrogenism (hirsutism or elevated androgens) and eumenorrhea (101 patients; 44.3%); normal androgens (acne or alopecia and eumenorrhea) (51 patients; 22.4%); isolated low SHBG (7 patients; 3.1%); nonclassical congenital adrenal hyperplasia (4 patients; 1.8% of total, 4.9% of patients undergoing cosyntropin stimulation tests); and ovarian tumor (2 patients; 0.9%).Ethinylestradiol and high-dose cyproterone acetate treatment lowered the hirsutism score to 53.5% of baseline at 1 year, and was also effective in treating acne and alopecia. The clinical benefit is ascribed to the peripheral antiandrogenic effect of cyproterone acetate as well as the hormone-suppressive effect of this combination. Salivary testosterone showed the most marked proportional decrease of all the androgens under treatment. Cost-effectiveness and tolerance of ethinylestradiol and high-dose cyproterone acetate compared well with other antiandrogenic drug therapies for hirsutism. The less potent therapy with spironolactone only, a peripheral antiandrogen without hormone-suppressive effect, was effective in treating isolated alopecia in patients with normal androgens.
多毛症、痤疮、脱发和月经过少是高雄激素血症的临床表现,高雄激素血症是育龄期女性最常见的内分泌疾病之一。因高雄激素血症的皮肤症状转诊至我们内分泌诊所的女性接受了实验室检查以评估激素水平,并接受了抗雄激素治疗。我们回顾性分析了6年间连续诊治的228例患者的治疗结果。多毛症患者的雄烯二酮、硫酸脱氢表雄酮(DHEAS)和唾液睾酮水平较高;性激素结合球蛋白(SHBG)水平较低;与脱发患者相比,月经过少的患病率更高,而痤疮患者的各项指标处于中间值。多毛症评分与雄烯二酮、DHEAS和唾液睾酮呈正相关,与SHBG呈负相关;唾液睾酮的相关系数最高。多毛症、脱发或痤疮患者的总睾酮水平无显著差异,且与多毛症评分无显著相关性。多毛症和月经过少是高雄激素血症最敏感的症状,没有单一的雄激素参数能够确诊所有高雄激素血症病例。中欧裔患者前来咨询时的多毛症评分比南欧裔患者轻。然而,两组之间的临床生物学相关性并无差异,这表明皮肤对雄激素的敏感性不存在差异。63例患者(27.6%)被诊断为多囊卵巢综合征,即高雄激素血症(多毛症或雄激素水平升高)和月经过少,与其他包括系统性卵巢超声检查的报告相比,这一诊断率被低估了。在少数病例中使用的盆腔超声以及促黄体生成素/促卵泡生成素比值均无助于将多囊卵巢综合征患者与其他诊断组区分开来。其他诊断组包括高雄激素血症(多毛症或雄激素水平升高)和月经正常(101例患者;44.3%);雄激素水平正常(痤疮或脱发且月经正常)(51例患者;22.4%);单纯SHBG水平低(7例患者;3.1%);非经典型先天性肾上腺皮质增生(4例患者;占总数的1.8%,接受促肾上腺皮质激素刺激试验患者的4.9%);以及卵巢肿瘤(2例患者;0.9%)。炔雌醇和高剂量醋酸环丙孕酮治疗1年后可使多毛症评分降至基线水平的53.5%,对治疗痤疮和脱发也有效。临床疗效归因于醋酸环丙孕酮的外周抗雄激素作用以及该联合用药的激素抑制作用。在所有接受治疗的雄激素中,唾液睾酮的下降比例最为显著。与其他治疗多毛症的抗雄激素药物疗法相比,炔雌醇和高剂量醋酸环丙孕酮的成本效益和耐受性良好。仅使用螺内酯这种效力较弱的疗法,即一种无激素抑制作用的外周抗雄激素药物,对雄激素水平正常患者的单纯脱发有效。