Vexiau P, Fiet J, Boudou P, Villette J M, Feutren G, Hardy N, Julien R, Dreux C, Bach J F, Cathelineau G
Diabetology and Endocrinology Department, Hôpital Saint-Louis, Paris, France.
J Steroid Biochem. 1990 Jan;35(1):133-7. doi: 10.1016/0022-4731(90)90157-n.
Dose-dependent hypertrichosis is a common dermatological side-effect affecting the majority of patients treated with cyclosporine A (CSA). Previous studies have not demonstrated the influence of CSA on specific sex hormone levels. The aim of this study is to investigate whether CSA increases the activity of 5 alpha-reductase, an enzyme which transforms androgens into dihydrotestosterone in peripheral tissues. The metabolite which best reflects this activity is 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (Adiol G). The study was carried out on 49 insulin-dependent diabetes patients participating in the double-blind "Cyclosporine-Diabète-France" clinical trial, of which 28 were treated with CSA (16 males and 12 females), and 21 received only placebo (10 males and 11 females). All patients underwent extensive clinical and laboratory evaluations prior to and during the present study. In addition to Adiol G, testosterone (T), dehydroepiandrosterone sulfate (DHEA S) and sex hormone-binding globulin (SHBG) were assayed. Levels of Adiol G increased significantly in CSA-treated groups: males, 11.86 +/- 2.58 vs 7.83 +/- 2.30 nmol/l; females, 4.48 +/- 2.70 vs 2.10 +/- 1.22 nmol/l; P less than 0.02 (comparison of means). There were no significant differences in this parameter before and during treatment in either the male or female placebo groups (paired t-test). During the treatment period, T, DHEA S, SHBG and the T/SHBG ratio did not significantly change with respect to their baseline values in any of the groups studied (comparison of means). Comparison (using paired t-test) showed a significant increase of DHEA S in CSA-treated groups: males, delta = 3.08 +/- 3.33 nmol/l, P less than 0.01; females, delta = 0.98 +/- 1.13 nmol/l, P less than 0.05. In conclusion, it is possible that CSA induces hypertrichosis or hirsutism by increasing 5 alpha-reductase activity in peripheral tissues. Nevertheless the role of increased DHEA S as a possible Adiol G precursor cannot be excluded.
剂量依赖性多毛症是一种常见的皮肤副作用，影响大多数接受环孢素A（CSA）治疗的患者。先前的研究尚未证明CSA对特定性激素水平的影响。本研究的目的是调查CSA是否会增加5α-还原酶的活性，该酶在外周组织中将雄激素转化为二氢睾酮。最能反映这种活性的代谢物是5α-雄烷-3α,17β-二醇葡萄糖醛酸苷（Adiol G）。该研究对49名参与双盲“环孢素 - 糖尿病 - 法国”临床试验的胰岛素依赖型糖尿病患者进行，其中28名接受CSA治疗（16名男性和12名女性），21名仅接受安慰剂（10名男性和11名女性）。所有患者在本研究之前和期间都接受了广泛的临床和实验室评估。除了Adiol G，还检测了睾酮（T）、硫酸脱氢表雄酮（DHEA S）和性激素结合球蛋白（SHBG）。CSA治疗组中Adiol G水平显著升高：男性，11.86±2.58 vs 7.83±2.30 nmol/l；女性，4.48±2.70 vs 2.10±1.22 nmol/l；P<0.02（均值比较）。男性或女性安慰剂组治疗前和治疗期间该参数均无显著差异（配对t检验）。在治疗期间，研究的任何组中T、DHEA S、SHBG以及T/SHBG比值相对于其基线值均无显著变化（均值比较）。比较（使用配对t检验）显示CSA治疗组中DHEA S显著增加：男性，δ=3.08±3.33 nmol/l，P<0.01；女性，δ=0.98±1.13 nmol/l，P<0.05。总之，CSA可能通过增加外周组织中5α-还原酶的活性来诱发多毛症或多毛。然而，不能排除DHEA S增加作为可能的Adiol G前体的作用。
