Bebb R A, Anawalt B D, Christensen R B, Paulsen C A, Bremner W J, Matsumoto A M
Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
J Clin Endocrinol Metab. 1996 Feb;81(2):757-62. doi: 10.1210/jcem.81.2.8636300.
Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.
在正常男性中使用高剂量睾酮（T）作为男性避孕药的研究，导致无精子症的发生率仅为50 - 70%。先前关于T与孕激素联合使用的研究显示了类似的无精子症发生率，但这些研究要么未设对照，要么使用的T剂量低于与最大程度抑制精子产生相关的剂量。我们进行了一项随机、安慰剂对照、单盲试验，比较36名年龄在20 - 42岁的正常男性（每组18人）接受6个月庚酸睾酮（100毫克，肌肉注射，每周一次）与相同剂量庚酸睾酮联合孕激素左炔诺孕酮（LNG；500微克，口服，每日一次）的情况。主要终点是诱导无精子症或严重少精子症（<300万精子/毫升）。T加LNG联合用药在抑制精子产生方面比单独使用T有效得多。到6个月时，T加LNG组67%（18人中的12人）和单独使用T组33%（18人中的6人）达到无精子症（P = 0.06）。T加LNG组94%（18人中的17人）出现严重少精子症或无精子症，而单独使用T组为61%（18人中的11人；P < 0.05）。T加LNG也比单独使用T更快地抑制精子产生。T加LNG组和单独使用T组达到无精子症的时间分别为9.9±1.0周和15.3±1.9周（平均值±标准误；P < 0.05）。接受T加LNG的男性血清高密度脂蛋白胆固醇下降21.7±3.6%（P < 0.05），而单独使用T组男性仅下降1.8±3.8%。T加LNG组平均体重增加5.3±0.8千克，单独使用T组平均体重增加2.3±0.9千克（P < 0.05）。两组痤疮和血红蛋白增加情况相似。我们得出结论，T与孕激素联合的激素疗法可能提供一种可逆的男性避孕方法，与单独使用T相比，其起效更快，诱导无精子症和严重少精子症更可靠。
