The male birth control shot may provide more choice for controlling male fertility in the future.
In the last 40 years, studies have demonstrated that reversible hormonal suppression of spermatogenesis - the process of sperm cell development - in men can prevent pregnancies in their female partners, although the commercial development of the product has been stalled.
In previous studies, testosterone management in men demonstrated birth control efficacy comparable with female methods. However, participants had to be given much greater doses than are typically found in the body and the method caused long-term adverse effects in healthy men.
While giving progesterone alongside can reduce the dose of testosterone, there have been few studies that have evaluated the efficacy and safety of such a combination. With 40 percent of all pregnancies worldwide unintended in 2012, better birth control options are required for men.
The aim of the new study was to test the effectiveness and safety of giving men injections of a long-acting progestogen called norethisterone enanthate, alongside replacement doses of a long-acting androgen called testosterone undecanoate, for preventing pregnancy in female partners.
The primary study objectives were to suppress the men's sperm count to below 1 million per milliliter through using birth control shots, maintaining sperm count suppression, and ensuring sperm count returns to normal limits.
The researchers also measured concentrations of steroid hormones and gonadotropins, monitored adverse events to determine the safety of the hormone concoction, and issued questionnaires to see if participants were accepting of using the method.
Clinical trial tests combined shot to reduce sperm count
"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 study author Dr. Mario Philip Reyes Festin, of the World Health Organization (WHO). "Our findings confirmed the efficacy of this contraceptive method previously seen in small studies."
A prospective, phase II, single-arm, multicenter study design was applied to test the safety and effectiveness of injectable birth control in 320 healthy men aged 18-45 years in stable, monogamous relationships with their 18-38-year-old female partners for at least a year.
Male participants were eligible for inclusion if they had normal sperm count at the start of the study, with no serious psychiatric diseases, sexually transmitted infections, no presence of illness, and a body mass index (BMI) between 20-32 kilograms per square meter.
Female partners were required to be healthy without reproductive issues, and not pregnant on entry to the suppression phase.
The couples were required to have intercourse twice a week, on average, with intent to remain in the relationship for the course of the study, with no desire for pregnancy within 2 years, and a willingness to accept a low, but unknown risk of pregnancy.
The men received two injections of 200 milligrams of norethisterone enanthate (NET-EN) and 1,000 milligrams of testosterone undecanoate (TU) from healthcare professionals every 8 weeks for up to 26 weeks to suppress their sperm counts.
Semen samples were provided after 8 and 12 weeks in the suppression phase and then every 2 weeks until a participant's sperm count was lowered to less than 1 million per milliliter in two consecutive tests. During this time, couples were instructed to use other non-hormonal birth control methods.
Couples were asked to rely on the male birth control shots after the criteria of a less than 1 million per milliliter sperm count was met. This stage was referred to as the efficacy phase of the study, during which the men continued to receive injections every 8 weeks for up to 56 weeks. Semen samples were provided every 8 weeks to make sure semen levels remained low.
After participants had stopped receiving injections, the team assessed how quickly their sperm counts recovered.
Birth control shot effective in 96 percent of continuing users
Of the 320 participants who received at least one injection, the hormones were effective in reducing the sperm count to less than 1 million per milliliter or less in 274 men by the end of 24 weeks.
The male birth control shot was found to be effective in nearly 96 percent of continuing users, with a total of four pregnancies occurring among the men's partners before the 16th week of the efficacy phase.
In 2011, recruitment of new study participants was stopped, and enrolled participants discontinued receiving injections and were transitioned to the recovery phase, due to the adverse events experienced outweighing the potential benefits.
Adverse events of concern were reports of mood changes, depression, pain at injection site, and increased libido. A total of 20 men discontinued the study due to side effects, six of which discontinued for changes in mood, and six discontinued for acne, pain or panic at first injection, palpitations, hypertension, and erectile dysfunction. Eight men discontinued for multiple reasons related to changes in mood.
More than 75 percent of participants reported willing to use the birth control shot at the end of the trial, despite the adverse effects.
Of the 1,491 adverse events that were reported by male participants, 38.8 percent were assessed as not being related to the birth control shot, including one suicide. Serious adverse events assessed as probably or possibly related to the study included one case of depression, one overdose of acetaminophen, and a participant that experienced an abnormally fast and irregular heartbeat after injections ceased.
Eight participants had not recovered to meet the criteria of return to fertility after 52 weeks in recovery phase. One volunteer did not recover within 4 years since his last injections.
"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. 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."
Dr. Mario Philip Reyes Festin
Dr. Festin and colleagues say that the study provides a valuable reference for future efficacy and safety trials of male birth control. "Such trials are urgently required to enable full assessment of the potential of this approach to new contraceptive product development," they conclude.