长效雄激素与孕激素合用抑制精子发生的剂量研究  

A dose-finding study of androgen combined with progestin for spermatogenic suppression in Chinese men

作　　者：谷翊群 童建孙 马鼎志 王兴海[2] 

机构地区：[1]国家计划生育委员会科学技术研究所,北京100081 [2]江苏省计划生育科学技术研究所,南京210029

出　　处：《生殖医学杂志》2002年第5期264-268,共5页Journal of Reproductive Medicine

基　　金：国家计划生育委员会科学技术研究所所级项目

摘　　要：目的 :观察人体对于醋酸甲孕酮 ( DMPA)与十一酸睾酮 ( TU )注射液合用的耐受程度 ,对安全性做出评估以及观察精子发生对 DMPA与 TU不同剂量合用的反应 ,推荐临床应用剂量配伍和注射间隔。方法 :2 5例年龄 2 5～ 45岁的正常男性志愿者 ,筛选合格后纳入该项临床试验。受试者随机分成 5组 ,每组 5例 ,包括 4个剂量配伍试验组( A组 :3 0 0 mg DMPA+1 0 0 0 mg TU,B组 :1 50 mg DMPA+50 0 mg TU,C组 :1 50 mgDMPA+1 0 0 0 mg TU,D组 :3 0 0 mg DMPA+50 0 mg TU)和 1个 1 0 0 0 mg TU单用对照组。整个试验周期为 56周 ,由 8周的对照期、2 4周的抑制期及 2 4周的恢复期组成。各组受试者每 2个月接受指定的剂量配伍注射 ,并定期进行随访。结果 :2 5名受试者均可耐受上述剂量注射、无严重不良反应。仅对照组 1例未达到无精子症 ,其余均达到无精子症。在抑制期 ,各组平均血清睾酮 ( T)浓度在正常范围内显著增加 ,各组平均血清黄体生成素( L H)和卵泡刺激素 ( FSH)水平显著降低 ,在恢复期内三者均逐渐恢复到基线水平 ;各试验组血红蛋白浓度在正常范围内增加 ;血清高密度脂蛋白在正常范围内降低。结论 :DM-PA与 TU不同剂量配伍以 2个月间隔注射均能有效地抑制中国人的精子发生 ,达无精子症水平。注射剂量可耐受 。Objective: To observe the tolerance, safety and efficacy of dose combinations of testosterone undecanoate (TU) and depot medroxyprogesterone acetate (DMPA) injected at bimonthly intervals for spermatogenesis suppression. Methods: A total of 25 normal volunteers after screening was recruited into this study. According to principle of randomization, subject was assigned to one of the 5 dose groups including 4 dose combination groups (Group A: 300 mg DMPA+1 000 mg TU, Group B:150 mg DMPA+500 mg TU, Group C:150 mg DMPA+1 000 mg TU, Group D:300 mg DMPA+500 mg TU) and 1 control group in which subjects only receive 1 000 mg TU injections. Each group contained 5 volunteers. This study consisted of an 8 week control period, a 24 week treatment period and a 24 week recovery period. During the study period, subjects attended the clinic to undergo general physical examination and sample collections according to the clinical protocol. Results: All the 25 subjects can tolerate injections at the dose combinations without serious adverse effects. Azoospermia was achieved in all 25 subjects, but one in control group. Mean serum T concentration during the treatment period increased significantly but still maintained within the normal reference range. The mean serum LH and FSH were significantly suppressed and returned to baseline levels during the recovery period. During the treatment period, the mean hemoglobin levels were incrased, HDL cholesterol was decreased, but still remained within the normal reference range. Conclusions: Bimonthly injections of TU/DMPA at the tested dose combinations can effectively suppress spermatogenesis to azoospermia in Chinese men without serious adverse effects. The lower dose combination (150 mg DMPA+500 mg TU) was recommended for expanded clinical trial or contraceptive efficacy study.

关 键 词：雄激素 孕激素 促性腺激素 精子密度 无精子症 少精子症 

分 类 号：R169.41[医药卫生—公共卫生与预防医学]