Steroid hormones for contraception in men

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 We wrote to authors of identified trials to seek unpublished or published trials that we might have missed.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.

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.