Ann Robinson 

Pills, thrills and polymer gels: what’s the future for male contraception?

For men, methods to prevent pregnancy have not evolved much since the condom. As vasectomy becomes less popular, could new methods including a testes-shrinking drug provide reliable, reversible birth control for men?
  
  

Colored Condoms.
There is clearly a huge gap in the market and an acceptable, reliable, reversible solution remains elusive. Photograph: Alamy Photograph: /Alamy

There are, despite an ancient and colourful history, only three forms of male contraception: condoms, withdrawal and vasectomy. The first condoms were used by Pasiphae, wife of King Minos of Crete, who used a goat’s bladder in her vagina to protect against his sperm, which was said to contain scorpions and serpents that killed his mistresses. The withdrawal method got bad press in the bible when Onan withdrew and spilt his seed rather than impregnate his widowed sister-in-law, Tamar. God was very displeased with this contraceptive method and killed him. Vasectomy was first offered to a man in Indiana in 1899 as a cure for his “excessive masturbation” – an alternative to the more conventional treatment of castration. The vasectomy was a great success and the physician reported that the patient “became more of a sunny disposition, brighter of intellect and ceased to masturbate”.

And we really haven’t progressed much since then. There is still no reversible male contraceptive, apart from condoms. Vasectomy – a surgical procedure, and by far the most reliable of the three – is also becoming less and less popular in the UK according to recent NHS statistics: rates fell from 30,000 NHS vasectomies in England in 2006/7, to 14,000 in 2012/13 (the most recent figures available). And, even if men do want one, provision of vasectomies on the NHS is being rationed in many areas.

There is clearly a huge gap in the market. New technologies are being developed, but an acceptable, reliable, reversible solution remains elusive. The challenge is that men produce so many sperm – around 1,000 per second. Women, however, only produce one egg per month, so suppressing an egg is always going to be easier than stemming the flood of sperm. And if a decent male contraceptive pill, injection or implant does come along, will men use it? In a study of attitudes to a male pill by men and women, both sexes were positive – though, unsurprisingly, women were more enthusiastic than men. Men in stable relationships were more receptive than men in casual sexual relationships and men with healthy lifestyles were more positive than less healthy men.

There’s still time for those men to change their minds, though, as it will be a while before this range of promising ideas will be fully developed:

The injection

Vasalgel is a polymer gel injected into the vas deferens (sperm duct) via the scrotum. It blocks sperm but lets the rest of the fluid ejaculate through, so it doesn’t protect against sexually transmitted diseases. A second injection dissolves and flushes out the gel, offering a potentially permanent but reversible method. Vasalgel is similar to a compound called Risug (or “reversible inhibition of sperm under guidance”) that is being trialled in India and appears to be safe and effective for humans, though Risug may never attract enough funding to come to market. Vasalgel has been tested on rabbits and primates and clinical trials are due to start in early 2016 – in the US, 26,000 men are on a waiting list to take part.

The clean-sheets pill

A drug is being developed in the UK based on phenoxybenzamine and thioridazine, which have been found to stop muscle contraction in the vas deferens so that sperm isn’t pushed forward. The rest of the ejaculate gets stalled, too, hence the “clean sheets”. The question is whether men would accept a dry ejaculate or, as one respondent to a survey put it, “all of the twitch, none of the spurt”. This method could also reduce transmission of HIV and deserves more attention but, again, funding is a problem. John Guillebaud, emeritus professor of family planning and reproductive health at University College London, says the team needs funding for studies in rams, then further trials if results are positive. “The fastest likely [development] is 10 years.” The idea is for a pill that men can take two to four hours before sex. “That’s fine for many,” says Guillebaud, but “might lead to conceptions when extra-frisky couples can’t wait that long” – they would be advised to use condoms until the pill kicks in. An implant version would give a longer-lasting effect, but normal semen would be restored within days of stopping the drug, but trials would be needed to test that.

The herb

This is a male contraceptive pill based on the active ingredient of gendarussa, a shrub native to Indonesia, where the drug has been developed. It works by blocking the enzyme that allows a sperm to penetrate an egg. Although further trials into effectiveness, dosage and safety are needed, trials involving about 300 men who took the extract for one to four months resulted in only one pregnancy.

The implant

A drug (anti-Eppin) binds to a protein on sperm (Eppin), and stops the sperm swimming towards the egg. Anti-Eppin could be delivered through an implant under the skin or orally. Tests assessing the drug’s safety are yet to be undertaken, but Dr Michael O’Rand, president of EppinPharma, the pharmaceutical startup developing the drug, says: “When we finish toxicology and non-human primate testing, we will be ready for a phase one human trial. However, this is several years away.”

He adds: “I would definitely take it.”

The genetic drug

JQ1 is a drug that turns off the BRDT gene responsible for sperm production in the testes. In animal studies, the drug takes six weeks to achieve temporary infertility and one to three months for fertility to return when the drug is stopped. Testicular size is reduced, but hormone levels and mating patterns are unaffected. It remains to be seen whether it will make human testes shrink and whether men would mind if it does.

The hormonal pill

Pills that combine two sex hormones (androgens and progestogens) act on the brain to shut down natural hormones that stimulate the testes to produce sperm. Tests have proved effective but have raised side-effects such as liver damage and variable effectiveness, especially between different ethnic groups.

The “bright” pill

A compound that temporarily inhibits the reproductive capacity of sperm has been developed by Professor Haim Breitbart (the pill’s name is a play on his surname) of Bar Ilan university in Israel. The drug makes mice infertile for one to three months, depending on the dose, with no impact on sex drive. “The mice behaved nicely; they ate and had sex. They were laughing and everything,” said Breitbart to the online magazine Popular Science. However, the professor says there is little chance of further development for now.

 

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