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More than 100 million women worldwide use a contraceptive pill. Now men are a step closer to protecting themselves in a similar way with the development of the first ever drug to offer non-hormonal and reversible male birth control. And as an added bonus, it doesn’t seem to affect sex drive either – at least in mice.

A non-hormonal option for male contraception is preferable to hormonal treatments currently in clinical trials, because the types of hormones that make men infertile have more severe side effects than those used in the female pill. The hormones can affect bone formation and liver abnormalities.

“Non-hormonal targets are urgently needed,” says James Bradner, a physician at the Dana-Farber Cancer Institute in Boston, Massachusetts. Now, he and his colleagues have developed a drug called JQ1, which inhibits a testes-specific protein called BRDT that is essential for fertility.


All sperm cells develop from germ cells. At an early stage of this process, BRDT enters the nucleus and switches on relevant parts of the genome that instruct the cell to mature into a sperm cell. JQ1 binds to BRDT at exactly the same part of the protein that sticks to the genome, preventing it from giving instructions to the cell. “It’s like removing the Post-it note that reminds the cell to turn into a sperm cell,” says Bradner.

When mice were administered daily injections of two different doses of JQ1 over a three- or six-week period, they saw at least a 90 per cent decrease in sperm count and at least a 75 per cent decrease in sperm cell motility. The decrease in the sperm count was so substantial at the higher dose that all of the mice became infertile. Importantly, though, within a month or two of stopping the drug treatment, mouse fertility was completely restored.

Still got mojo

No significant side effects occurred, and testosterone levels appeared normal. Mating behaviours were also unaffected. “There was no obvious effect on the mojo of the animals,” says Bradner.

Drug derivatives of JQ1 are currently being tested in clinical trials for people with cancer. Bradner’s team have funding from the National Institutes of Health to develop a similar drug for BRDT.

“This is a refreshingly novel approach, and the studies are of top quality and are highly convincing,” says Richard Sharpe, who specialises in male reproductive health at the University of Edinburgh, UK. “The approach used appears highly effective and fully reversible, at least in the relative short-term. And there are no obvious adverse effects in offspring sired by treated males after they had been taken off the treatment.”

Sharpe highlights several hurdles on the route to a human equivalent of the drug, such as creating an oral version rather than the injectable form used in the rodent trials. It is also important to ensure the drug is reversible in the long-term, and that it leads to no adverse effects in offspring conceived at a later date. However, he adds that it is the most promising new approach that he has seen.

“Developing a small molecule as a contraceptive is highly challenging considering that the users will accept only very minor side effects, considering that they are not sick,” says Aarnoud C. van der Spoel at Dalhousie University in Halifax, Canada. He says that further investigation into the long-term effects and side effects of the drug are critical.

“[However], the work is impressive, with highly promising results,” says van der Spoel. “There is a world-wide unmet need for alternative approaches for family planning, and additional methods to achieve this goal are to be applauded.”

Journal reference: Cell, DOI: 10.1016/j.cell.2012.06.045