Grimes D A, Lopez L M, Gallo M F, Halpern V, Nanda K, Schulz K F
Family Health International, Clinical Research, Post Office Box 13950, Research Triangle Park, North Carolina 27709, USA.
Cochrane Database Syst Rev. 2007 Apr 18(2):CD004316. doi: 10.1002/14651858.CD004316.pub3.
Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so 'add-back' therapy is needed.
To summarize all randomized controlled trials of male hormonal contraception.
We searched the computerized databases CENTRAL, MEDLINE, EMBASE, POPLINE, and LILACS (each from inception to March 2006) for randomized controlled trials of hormonal contraception in men. We wrote to authors of identified trials to seek unpublished or published trials that we might have missed.
We included all randomized controlled trials in any language that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups. All trials identified included only healthy men with normal semen analyses.
Azoospermia (absence of spermatozoa on semen examination) was the primary outcome measure. Data were insufficient to examine pregnancy rates and side effects.
We found 30 trials that met our inclusion criteria. The proportion of men who achieved azoospermia varied widely in reports to date. A few important differences emerged from these trials: levonorgestrel implants combined with injectable testosterone enanthate (TE) were more effective than levonorgestrel 125 microg daily combined with testosterone patches; levonorgestrel 500 mug daily improved the effectiveness of TE 100 mg injected weekly; desogestrel 150 mug was less effective than desogestrel 300 mug (with testosterone pellets); testosterone undecanoate (TU) 500 mg was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel implants); norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when given every 8 weeks versus 12 weeks; four implants of 7-alpha-methyl-19-nortestosterone (MENT) were more effective than two MENT implants. Several trials showed promising efficacy in terms of percentages with azoospermia. Three examined desogestrel and testosterone preparations or etonogestrel (metabolite of desogestrel) and testosterone, and two examined levonorgestrel and testosterone.
AUTHORS' CONCLUSIONS: No male hormonal contraceptive is ready for clinical use. Most trials were small exploratory studies. As a result, their power to detect important differences was limited and their results imprecise. In addition, the definition of oligozoospermia has been imprecise or inconsistent. To avoid bias, future trials need more attention to the methodological requirements for randomized controlled trials. More trials with adequate power would also be helpful.
男性激素避孕一直是一个难以实现的目标。对男性施用性类固醇可通过对垂体和下丘脑的作用来抑制精子生成。然而，这种方法也会降低睾酮的生成，因此需要“补充”疗法。
总结男性激素避孕的所有随机对照试验。
我们检索了计算机化数据库CENTRAL、MEDLINE、EMBASE、POPLINE和LILACS（均从建库至2006年3月），以查找男性激素避孕的随机对照试验。我们致函已识别试验的作者，以寻找可能遗漏的未发表或已发表试验。
我们纳入了所有语言的随机对照试验，这些试验比较了一种类固醇激素与另一种避孕方法。我们排除了非甾体类男性避孕药，如棉酚。我们纳入了安慰剂和活性方案对照组。所有识别出的试验仅纳入精液分析正常的健康男性。
无精子症（精液检查无精子）是主要结局指标。数据不足以检查妊娠率和副作用。
我们发现30项试验符合我们的纳入标准。迄今为止的报告中，实现无精子症的男性比例差异很大。这些试验出现了一些重要差异：左炔诺孕酮植入剂联合庚酸睾酮注射液（TE）比每日125微克左炔诺孕酮联合睾酮贴片更有效；每日500微克左炔诺孕酮提高了每周注射100毫克TE的有效性；150微克去氧孕烯比300微克去氧孕烯（联合睾酮丸剂）效果差；500毫克十一酸睾酮（TU）比1000毫克TU（联合左炔诺孕酮植入剂）产生无精子症的可能性小；每8周而非12周给予200毫克庚酸炔诺酮联合1000毫克TU导致更多无精子症；4枚7-α-甲基-19-去甲睾酮（MENT）植入剂比2枚MENT植入剂更有效。几项试验在无精子症百分比方面显示出有前景的疗效。三项试验研究了去氧孕烯和睾酮制剂或依托孕烯（去氧孕烯的代谢物）和睾酮，两项试验研究了左炔诺孕酮和睾酮。
尚无男性激素避孕药可用于临床。大多数试验是小型探索性研究。因此，它们检测重要差异的能力有限，结果也不精确。此外，少精子症的定义一直不精确或不一致。为避免偏倚，未来试验需要更多关注随机对照试验的方法学要求。更多有足够效力的试验也会有所帮助。
