Written by Lucy Wilson and Greg Kopf, FHI 360
The future of male contraception has been big news recently, not only here on the CTI Exchange blog, but across the global news media. And the news got even bigger in the last few weeks with the publication of study data demonstrating promising efficacy rates of an injectable hormonal contraceptive for men.
Among study participants receiving the combined progestin and testosterone injections, 96% had sperm concentrations levels low enough to be considered effective at preventing pregnancy.
However, side effects experienced by participants led an external peer-review committee to conclude that the potential benefits did not outweigh the potential risks. The adverse events reported in the study included depression, mood changes, pain at the injection site, and increased libido.
These side effects may not sound all that serious at first, but further examination of specific adverse events gives one pause. There was one suicide and one attempted suicide. Mood changes included reports of hostility and aggression. While the scientists leading the study state that the link between these incidents and the study drug is not clear, it is hard to rule out a causal link.
Several articles equate the risk of side effects in this study to the risk of side effects for female hormonal contraception, like the pill. But comparisons between the two are difficult to interpret. Understanding the causal relationships between contraception and side effects, especially those that affect a person’s mental health, is extremely challenging and will require a great deal of additional research. Given the lack of current investment in contraceptive development by the pharmaceutical industry, further exploration of such relationships is unlikely.
Contraceptives are used by healthy men and women for extended periods of time during their reproductive lifespans. As such, the safety requirements for getting new contraceptives approved by the US FDA and other regulatory bodies is much higher than for a drug that a person takes to treat an illness. Potential links to suicide are not likely to pass muster at the FDA.
The study was a prospective, phase II, single-arm study conducted at 10 sites in 7 countries from 2008-2012. The 320 study participants received intramuscular injections of norethisterone enanthate (NET-EN; 200 mg) and testosterone undecanoate (TU; 1000mg) every 8 weeks. The men were healthy, aged 18-45 years, and like their female partners, had no known fertility problems.
The main study objectives were to evaluate the suppression of spermatogenesis, which occurred in 96% of men as measured by sperm concentrations, and the level of contraceptive protection as assessed by the number of pregnancies among the couples in the study “efficacy” phase (once suppression of spermatogenesis had been achieved). Four pregnancies occurred among the partners of the 266 male participants. This translates to a rate of 1.57 pregnancies per 100 continuing users in one year. The contraceptive efficacy seen in this study is encouraging given that short-acting contraception for men – condoms and withdrawal, have efficacy rates of 2 and 4 pregnancies per 100 users, respectively. Vasectomy, a permanent male contraceptive method, and many methods of reversible contraception for women, including the IUD, implant, and DMPA injection, have less than 1 pregnancy per 100 users in the first year.
While the difference may not look like much, it becomes significant over the reproductive lifespan of a man or woman. After 10 years, 14 out of 100 couples using this male method would become pregnant, while with those using the female methods described above, less than 3 couples out of 100 would become pregnant. These figures represent pregnancy rates assuming “perfect” use of the respective contraceptive. “Typical” or “actual” use rates for contraceptives translate to a greater rate of unintended pregnancies, especially for those methods that require end-user involvement such as returning to a healthcare provider for repeat injections.
Contraceptive effectiveness rates are not well understood by most contraceptive users. Most people expect all contraceptive methods to be 100% effective at preventing pregnancy. This misunderstanding is especially important to understand in the context of a male contraceptive method. Imagine a couple is relying on a male method of contraception and assume it to be 100% effective. If the woman becomes pregnant, the man may accuse her of infidelity. Any male method of contraception must be at least as effective as the most effective form of female contraception.
The good news coming from this study are the data related to acceptability. While some side effects were deemed alarming, the most common ones were acne, injection site pain, and increases or decreases in libido with nearly 50% of men experienced at least one such side effect. Nonetheless, willingness to use a method like this one was high, with over 75% of the participants, both the men and their female partners, satisfied or very satisfied with this method. This demonstrates that men, just like women, are willing to accept some side effects from a contraceptive method.
Given the results of this study, does this male hormonal contraceptive method have a shot at making it to market? Likely not. But this study does give us hope for the future of male contraceptive research. Not only are the acceptability data promising, but we can learn a great deal about how this testosterone and progestin combination function in terms of efficacy and side effects. Re-formulations and/or different active pharmaceutical ingredients could yield better results.
Little progress has been made to date in bringing a male contraceptive method to market. The fact that this product was able to progress this far along in clinical trials with good–if not good enough results– is very welcome news both to the field and to couples desiring additional contraceptive options.