Arlington, VA – Key results of a CONRAD and WHO-sponsored contraceptive study reveal that a combination of hormones delivered via injection to male participants were effective in preventing pregnancy. This Phase II study was the first large-scale, multi-country trial of a combination regimen of hormones to investigate contraceptive efficacy in men. A combination of a long-acting progestin, norethisterone enantate (NET-EN), and a long-acting androgen, testosterone undecanoate (TU) were administered by injection every 8 weeks and relied on the study regimen as their method of contraception.
Final results, published today in the Journal of Clinical Endocrinology & Metabolism, show that the regimen led to a near-complete and reversible suppression of spermatogenesis, or sperm production. The contraceptive efficacy compared favorably to other reversible methods available for men. However, the frequency of side effects was relatively high, which included: acne, injection site pain, increased libido, and mood disorders. Due to these adverse events, the study was terminated before its completion.
Out of 320 participants who began the study regimen, 95.9 per 100 continuing users suppressed to sperm concentration ≤ 1 million/ml within 24 weeks, a threshold indicative of low fertility in previous studies. Those men proceeded into a 12-month contraceptive efficacy phase. Four pregnancies occurred among the partners of the 266 male participants who transitioned into the efficacy phase, with the rate of 1.57 per 100 continuing users. This was followed by a recovery phase, in which the men were monitored for return to sperm levels indicative of fertility. Men whose sperm concentrations were not adequately suppressed initially, whose sperm levels rose above the threshold during the efficacy phase, or withdrew for any reason entered the recovery phase as well. The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users, with a combined method failure rate of 7.5%, which is comparable to female oral contraceptive methods, as typically used.
Participants were healthy men aged 18-to-45 years, and their 18–to-38 year-old female partners, both without known fertility problems. The study involved ten sites in seven countries including Australia, Chile, Germany, India, Indonesia, Italy and United Kingdom.
Despite the higher than expected number of adverse events, many participants expressed their satisfaction with the method and indicated that their partners were relieved that they did not have to bear the burden of contraception themselves. In addition, some men indicated their disappointment that they would not continue to receive the study drugs. Responses to key acceptability questions by male participants and female partners demonstrated high rates of satisfaction with the method of contraception applied in this study. Most of the couples would use this method of contraception, with 82.3% of male participants and 76% of female participants responding affirmatively.
It has been a long-standing goal of many researchers and organizations to develop safe, effective, reversible and acceptable hormonal regimens for male contraception. Given the efficacy and acceptability of this method, despite side effects, there continues to be a strong rationale for continuing research.
The TU NET-EN study was co-sponsored and funded by UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (HRP, World Health Organization, Geneva, Switzerland) and CONRAD (Eastern Virginia Medical School, Arlington, USA, using funding from the Bill & Melinda Gates Foundation and U.S. Agency for International Development). NET-EN and TU were provided free of charge by Schering AG (now Bayer Pharma AG, Berlin, Germany). The Center of Reproductive Medicine and Andrology (University of Münster, Germany) served as the central laboratory for hormone analysis. Global Research Services, LLC (now GRS Worldwide, Rockville, MD, USA), served as CRO.
An unedited online version of the manuscript ahead of print is available.