Knuth U A, Hano R, Nieschlag E
J Clin Endocrinol Metab. 1984 Nov;59(5):963-9. doi: 10.1210/jcem-59-5-963.
To test the effects of antiandrogen treatment on the endocrine system 20 normal young men were treated with 750 mg/day flutamide [4-nitro 3'-trifluoromethylisobutyranilide (FLU)] or 100 mg/day cyproterone acetate (CPA) for 14 days followed or preceded by a placebo treatment of the same duration 4 weeks apart. Allocation of both drugs and sequence of active and placebo substance was by random number in a double blind design. On days 1 and 14 two basal blood samples were obtained 15 min apart followed by an iv injection of 25 micrograms GnRH and 10 mg metoclopramide (MTCL). Subsequently blood samples were taken after 25, 45, 60, and 90 min. On day 8 the GnRH/MTCL test was performed after 13 basal blood samples were obtained to establish a baseline for PRL concentrations unbiased by short term stress. After 14 days of FLU treatment, serum testosterone (T) increased significantly [17.4 +/- 1.4 (SE) vs. 26.9 +/- 1.5 nmol/liter, as well as estradiol (E2) concentrations (144 +/- 12 vs. 177 +/- 20 pmol/liter). Dihydrotestosterone increased slightly after 14 days of FLU administration (1.59 +/- 0.14 vs. 1.98 +/- 0.30 nmol/liter). At the same time basal LH concentrations were significantly elevated (5.9 +/- 0.5 vs. 8.6 +/- 0.6 ng/ml), whereas FSH levels were not affected (2.8 +/- 0.6 vs. 2.8 +/- 0.6 ng/ml). No changes in PRL values were detected throughout treatment with FLU. The effect of CPA was quite different. At the end of the treatment phase, serum T levels were reduced considerably (14.6 +/- 1.8 vs. 3.3 +/- 0.4 nmol/liter). Serum E2 decreased similarly (95 +/- 13 vs. 35 +/- 6 pmol/liter). Conversion of T to dihydrotestosterone was also diminished significantly (1.72 +/- 0.33 vs. 1.14 +/- 0.33 nmol/liter). Both gonadotropins were significantly depressed after 14 days of CPA administration (LH, 5.6 +/- 0.7 vs. 2.8 +/- 0.4 ng/ml; FSH, 2.4 +/- 0.3 vs. 1.4 +/- 0.2 ng/ml). Basal PRL levels were not affected, although the response of MTCL was reduced at the end of the treatment phase. Both drugs reduced the response of LH and FSH to GnRH administration.
为了测试抗雄激素治疗对内分泌系统的影响，20名正常青年男性接受了以下治疗：每天服用750毫克氟他胺[4-硝基-3'-三氟甲基异丁酰苯胺（FLU）]或每天服用100毫克醋酸环丙孕酮（CPA），持续14天，在前后相隔4周的时间里，有相同时长的安慰剂治疗。两种药物的分配以及活性物质和安慰剂的给药顺序均采用随机数字法进行双盲设计。在第1天和第14天，相隔15分钟采集两份基础血样，随后静脉注射25微克促性腺激素释放激素（GnRH）和10毫克甲氧氯普胺（MTCL）。随后在25、45、60和90分钟后采集血样。在第8天，在采集13份基础血样后进行GnRH/MTCL测试，以建立不受短期应激影响的催乳素（PRL）浓度基线。氟他胺治疗14天后，血清睾酮（T）显著升高[17.4±1.4（标准误）对26.9±1.5纳摩尔/升]，雌二醇（E2）浓度也升高（144±12对177±20皮摩尔/升）。氟他胺给药14天后，双氢睾酮略有升高（1.59±0.14对1.98±0.30纳摩尔/升）。同时，基础促黄体生成素（LH）浓度显著升高（5.9±0.5对8.6±0.6纳克/毫升），而促卵泡生成素（FSH）水平未受影响（2.8±0.6对2.8±0.6纳克/毫升）。在整个氟他胺治疗过程中，未检测到PRL值的变化。醋酸环丙孕酮的作用则大不相同。在治疗阶段结束时，血清T水平大幅降低（14.6±1.8对3.3±0.4纳摩尔/升）。血清E2也同样下降（95±13对35±6皮摩尔/升）。T向双氢睾酮的转化也显著减少（1.72±0.33对1.14±0.33纳摩尔/升）。醋酸环丙孕酮给药14天后，两种促性腺激素均显著降低（LH，5.6±0.7对2.8±0.4纳克/毫升；FSH，2.4±0.3对1.4±0.2纳克/毫升）。基础PRL水平未受影响，尽管在治疗阶段结束时甲氧氯普胺的反应有所降低。两种药物均降低了LH和FSH对GnRH给药的反应。
