EXECUTIVE SUMMARY

Men may be able to use birth control shots to prevent pregnancy in their female partners, data suggest in a just-published Phase II study. Researchers studied injections of 200 mg of a long-acting progestogen, norethisterone enanthate and 1,000 mg of a long-acting androgen, testosterone undecanoate.

  • Men have few choices when it comes to controlling their own fertility.
  • Available methods for men include condoms, vasectomies, and withdrawal.
  • The Male Contraception Initiative, a nonprofit organization, is working with researchers across the globe to make male contraceptive options a reality.

Men may be able to use birth control shots to prevent pregnancy in their female partners, data suggest in a just-published Phase II study. More options would be welcome as men have few choices when it comes to controlling their own fertility. Available methods for men include condoms, vasectomies, and withdrawal.

To conduct the prospective single arm, multi-center study, researchers enrolled 320 healthy men 18-45 years of age. Study participants had been engaged in monogamous relationships with female partners between the 18-38 years of age for at least one year. All men underwent testing to ensure they had a normal sperm count at the start of the study.

To suppress sperm counts, study participants received injections of 200 mg of a long-acting progestogen, norethisterone enanthate and 1,000 mg of a long-acting androgen, testosterone undecanoate, for up to 26 weeks. Clinicians administered two injections every eight weeks. Participants initially provided semen samples after eight and 12 weeks in the suppression phase and then every two weeks until they met the criteria for the next phase. During this time, participants and their partners were instructed to use other non-hormonal birth control methods.

Once a participant’s sperm count was lowered to less than 1 million/mL in two consecutive tests, the couple was asked to rely on the shots for birth control. During this period, the men continued to receive injections every eight weeks for up to 56 weeks. Participants provided semen samples every eight weeks to ensure their sperm counts stayed low. Once participants stopped receiving the injections, monitoring was performed to see how quickly their sperm counts recovered.

Data indicate the hormones were effective in reducing the sperm count to 1 million/mL or less within 24 weeks in 274 participants. During the efficacy phase of up to 56 weeks, four pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% confidence interval, 0.59-4.14).1

“The study found it is possible to have a hormonal contraceptive for men that reduces the risk of unplanned pregnancies in the partners of men who use it,” says Mario Philip Reyes Festin, MD, a medical officer at the Human Reproduction team at the Department of Reproductive Health and Research within the World Health Organization and a study co-author. “Our findings confirmed the efficacy of this contraceptive method previously seen in small studies.”

Researchers halted the enrollment of new study participants in 2011 due to the rate of reported adverse events, particularly depression and other mood disorders. Reported side effects included injection site pain, muscle pain, increased libido, and acne. Twenty men dropped out of the study due to side effects. Despite the adverse effects, more than three-quarters of participants reported willingness to use this method of contraception at the conclusion of the trial.

Of the 1,491 reported adverse events, about 40% were found to be unrelated to the contraceptive injections. These included one death by suicide, which was assessed not to be related to the use of the drug. Serious adverse events that were assessed as probably or possibly related to the study included one case of depression, one intentional overdose of acetaminophen, and one incident of an abnormally fast and irregular heartbeat after injections ended.

“More research is needed to advance this concept to the point that it can be made widely available to men as a method of contraception,” Festin observes. “Although the injections were effective in reducing the rate of pregnancy, the combination of hormones needs to be studied more to consider a good balance between efficacy and safety.”

If the desire is to bring new male contraceptives to market quickly, funding must be diversified, says Aaron Hamlin, MPH, Esq., executive director of the Male Contraception Initiative. This nonprofit organization is working with researchers across the globe to make male contraceptive options a reality. (Editor’s Note: More information about the organization is available at: http://bit.ly/2fXlx9r.)

The recent clinical trial’s halt is a reminder of just why funding must be diversified, Hamlin says. Hormonal options have a lot of challenges; mood side effects have been persistent in other studies as well, he notes. The study is not the first male hormonal contraceptive study with incidents of attempted suicide, Hamlin adds.

“Plus, there are nonresponders, and for those men who do respond, they have to wait many months for their fertility to return — or, in rare cases, never return — that’s going to be tough for some men to take on,” Hamlin explains. “That so many men have opted to go through this is a testament to the demand for a new male contraceptive.”

Although some of these problems can be resolved, other hormonal issues appear to be unavoidable, Hamlin argues. Focusing on sperm production requires a multi-month wait before the contraceptive is effective; for example, the current trial took six months before 96% of the men’s sperm count went below the 1-million-per-milliliter target, he notes.

Although no drug is void of side effects, non-hormonal methods at least offer the potential to avoid these particular issues, as well as later-stage targets such as sperm motility, Hamlin says. There, the ability is for the contraceptive to be quicker-acting, he adds.

“Other targets include vas blockage, fertilization capacity, and stopping muscular contractions in the vas,” Hamlin continues. “We’d expect men to be more likely to find a quick-acting contraceptive acceptable — there are options here.”

Today, clinicians have withdrawal, condoms, and vasectomies to offer men, says Robert Hatcher, MD, MPH, professor emeritus of gynecology and obstetrics at Emory University School of Medicine in Atlanta.

“The hormonal injection described above, it appears to me, hold virtually zero likelihood for providing a fourth contraceptive approach for men,” he states.

REFERENCE

  1. Behre HM, Zitzmann M, Anderson RA, et al. Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab 2016; doi:10.1210/jc.2016-2141.