Male contraceptive jab tested

A new male contraceptive “is as effective as the female pill in preventing pregnancy”, the_ Daily Express_ has claimed. These findings come from a study of 1,045 healthy, fertile Chinese men aged 20 to 45 who received monthly injections of testosterone over two and a half years. Only 1% of the men’s wives became pregnant during the study.

Although this is a large study, it does have a number of limitations. Further studies will be needed to confirm its results in different populations and look at long-term safety before this treatment becomes widely available.

Even if this contraceptive method was found to be safe it would require monthly injections by a health professional. This may not be practical for some men, and these injections would not protect against sexually transmitted infections. Men and women in a new relationship are still advised to use condoms.

Where did the story come from?

Professor Yiqun Gu and colleagues from National Research Institute for Family Planning in Beijing and other research institutions in China carried out this research. The study was funded by HRP, a United Nations and World Bank research programme on human reproduction. It was published in the peer-reviewed Journal of Clinical Endocrinology and Metabolism .

What kind of scientific study was this?

This was a case series looking at how effectively an injectable solution containing testosterone undecanoate functioned as a male contraceptive.

Previous trials have shown that weekly testosterone injections provided effective, reversible contraception for up to 12 months. However, it was thought that weekly injections would not be practical and acceptable to men. This current study therefore looked at the effectiveness of longer-acting monthly testosterone injections.

The researchers enrolled 1,045 healthy, fertile Chinese men aged 20 to 45 from family planning centres across China. To be eligible for inclusion, men had to have fathered at least one child in the previous two years and have normal results in physical and laboratory testing, including sperm tests. The men’s partners were aged 18 to 38, had normal fertility and reported being in stable relationships with the male participants.

The men initially received a “loading” dose of 1,000mg testosterone into the buttocks, followed by monthly injections of 500mg testosterone undecanoate given by research nurses. For the first six months (the ‘suppression’ phase), men were required to use barrier contraceptive methods (for example condoms) to prevent pregnancy.

The men gave semen samples at three, five and six months into the study, and their partners received a pregnancy test at the end of this suppression phase. Only men whose partners were not pregnant and who had two successive semen samples with very low sperm concentrations were allowed to enter the 24-month ‘efficacy’ phase of the study. A very low sperm count was defined as one million or fewer sperm per millilitre, compared to 20 million sperm per millilitre found in normal semen.

During the efficacy phase men continued to receive monthly testosterone injections and were not allowed to use any other form of contraceptive. They gave semen and blood samples, and were examined every three months. Men whose partners became pregnant were withdrawn from the study. The researchers looked at the rates of contraceptive failure (partners becoming pregnant) during the efficacy phase, and of “sperm rebound” (sperm concentrations over one million per millilitre on two samples).

After the efficacy phase or after discontinuing the study for any reason, the men entered a 12-month recovery phase. During this period the men attended the clinic for examination and to provide blood and semen samples every three months. During the recovery phase the men could use contraception to prevent pregnancy if they wished.

What were the results of the study?

One hundred and ninety men (18%) withdrew from the study in the suppression phase. This included 43 men (4.1%) whose sperm count did not drop below one million per millilitre of semen, and eight men (0.8%) who had adverse events such as skin rashes, fever or fear of injection. There were 19 pregnancies (1.8%) in the suppression period due to failure and non-use of barrier methods of contraception.

After these exclusions this left 855 men who entered the 24-month efficacy phase, which 733 men completed. Ten men (1.2%) experienced sperm count rebound during this phase, and there were nine pregnancies (1.1%). Eighteen men (2.1%) withdrew from the study due to adverse events, but none of the adverse events was considered serious. Reasons for withdrawal included fear of injections, skin rashes, acne, changes in libido and increases in blood pressure. During the efficacy period the men’s body weight increased by between 0.4 and 1.6kg, and their testis volume reduced by 4-16%.

After discontinuing the injections, it took an average (median) of 182 days for the men’s sperm count to return to their pre-study level and 230 days for their sperm output to return to a normal level (over 20 million per millilitre).

Eight hundred and twenty-six men completed the 12-month recovery period. The sperm counts of 17 men (2%) did not return to normal levels in this period, but in 15 men their levels returned to normal after a further three-month period.

What interpretations did the researchers draw from these results?

The researchers concluded that “monthly injection of 500mg [testosterone undecanoate] provides safe, effective, reversible and reliable contraception in a high proportion of healthy fertile Chinese men”.

What does the NHS Knowledge Service make of this study?

This large study suggests the high contraceptive efficacy of monthly testosterone injections in Chinese men. This study did not compare a group using testosterone injections to a control group using no contraception or other contraceptive methods. There are some important points to note:

• Although it was reported that other forms of contraception were not allowed, it is unclear whether the men’s partners were questioned about their contraceptive use to ensure that they were not using any contraceptive methods themselves that the men did not know about.
• The authors did not report how they checked for pregnancies during the efficacy phase. If they relied solely on the men’s own reports, some pregnancies may have been missed or gone unreported.
• As the men only received the injections for 30 months and were followed up for a year after discontinuation, it is not possible to say whether there are any side effects in the longer term or from longer periods of use. Testosterone levels may affect risk of cardiovascular and prostate disease, so researchers will particularly want to assess long-term effects on these diseases.
• The authors point out that the contraceptive success rate in their study was higher than that seen in studies in other populations, and suggest that this may be due to ethnic differences. Further studies will be needed to confirm these findings in other populations.
• This method of contraception will not prevent transmission of sexually transmitted diseases.
• The injections were given by nurses in family planning clinics. It is unclear what proportion of men would be willing to attend a clinic to receive monthly contraceptive injections, or how high compliance and contraceptive success rates would be if men injected themselves.

Ultimately, the best way of testing the long-term efficacy and safety of testosterone injections will be by performing comparative studies (such as randomised trials) against current contraceptive methods.