Despite decades of research no male contraceptive ready for market

NOT long before Christmas, newspapers, radio stations and TV networks were abuzz with some exciting news: the male pill could soon be a reality.

Researchers at Monash University in Melbourne had discovered a way to block a couple of proteins that controlled the movement of sperm. The result was complete but temporary infertility — there would be no long-term effects on the “viability of sperm or the sexual or general health of men”, assured Dr Sabatino Ventura, the head researcher.

The medication would be taken orally, just like the female contraceptive pill, and that was not the only attractive feature. Crucially — for men at least — taking it would have no impact on libido or sexual behaviour. “If anything, their performance should improve with the strategy we are using,” Ventura told Australian TV.

On the telephone, Ventura first had the idea for the treatment as a post-graduate researcher 25 years ago — he’s 49 now — and since then he had been “waiting for technology to catch up with me”. He never fully believed the day would come when he would be fielding calls from across the globe

Male contraception is tricky, Ventura explains, because men make about 1,000 sperm every second and you need to stop them all. Women produce one egg a month, so interfering with that is a simpler medical challenge. “Remember,” he notes, “if just one of those sperm gets through to the egg, you’ve lost your contraception.”

Ventura’s research was praised by fellow scientists for offering an elegant solution to this longstanding problem. I ask him for the most unscientific explanation for how his pill would work. He tells me to picture an aeroplane: the plane taking off is ejaculate leaving a male body, but before that, it has to be loaded up with passengers, ie sperm. His medication silences the announcement in the airport terminal telling people to board. “So the plane’s taking off,” he says, “but it’s got no passengers on it.”

It does sound ingenious. But then I speak with Elaine Lissner, founder of a San Francisco-based non-profit group called the Male Contraception Information Project. Lissner, a fast-talking woman in her 40s, is keen to highlight some of the hurdles that Monash University’s male pill would face before eventually one day coming to market.

The Australian research was conducted on mice who’d had their DNA tweaked: what the scientists have to do now is create a human equivalent that relies on a chemical component rather than genetic tampering. This would be a significant undertaking that could take a well-funded team at least a decade.

“This is very early-stage work,” Lissner warns. “When you hear ‘five to 10 years’ you might as well figure ‘maybe never’. If we actually want a male contraceptive, we have to finish the job on what we’ve already started.”

Lissner is not entirely impartial. She has invested heavily in procuring the international rights for a male contraceptive treatment developed in India called Vasalgel. Nevertheless it’s hard to dispute her circumspection. The news agenda loves the story of a “new male pill”: there is a huge rush of interest in a scientific paper that hits the headlines. But then it disappears, never to be heard of again.

Male contraception has been a preoccupation for longer than you might imagine. In the 5th century BC, Hippocrates had some success with heating a man’s testicles in a hot bath. The father of western medicine might not have had proof that sperm is much happier several degrees below a man’s core body temperature — we learned that in the 20th century — but the “heat method” has become an enduring and often successful way of preventing conception.

Dr Marthe Voegeli, a Swiss doctor working in India from the 1930s to the 1950s, advocated that men put their testicles in a shallow bath warmed to 46.5C for 45 minutes a day for three weeks. Her tests — on hundreds of Indian men and a small handful of English, American and Scottish volunteers — indicated that this would lead to around six months of sterility.

Other esoteric methods have shown potential, too. Pedanius Dioscorides, a Greek physician who worked as a Roman army doctor in the 1st century, detailed in his five-volume De Materia Medica – which would become a health bible for the next 1,500 years — that drinking juice made from cannabis would reduce sexual potency. Recent tests, on rats, have shown that marijuana can reduce sperm counts by half.

Academics working in the area have traditionally been the butt of jokes from their peers. “Research on it is not prestigious,” states the Male Contraception Information Project’s website, “and often earns scientists derision from their colleagues.”

There’s a suggestion that a dismissive attitude still persists to this day, according to Ventura.

“You’ve already got a good female contraception, so people don’t think we need a male equivalent,” he says. “It’s more like: ‘Oh, that would be handy, but we could probably do with curing a whole lot of other diseases beforehand.’ If you are writing a grant proposal to develop drugs to cure cancer or other chronic illnesses, you have a better argument because you are saving people’s lives.”

Back in November 2006 Dr Nnaemeka Amobi, a physiologist at King’s College London, was the hot-shot scientist who had cracked the male pill – the product of 17 years in development. Dr Amobi’s research was also at a very early stage – it had yet to be tested on animals even. It derived from research published in 1968 about thioridazine, a drug used to treat schizophrenia. Thioridazine had fallen out of favour as a mental-health treatment — it could cause an irregular heartbeat that led to sudden death and was withdrawn from use in the UK in 2005 — but it did have a surprising side-effect: male patients who took it typically experienced their orgasms without any ejaculate.

Guillebaud, a lively 73-year-old who was born in Burundi and now lives in Oxford, explains: “So this man went to a psychiatrist and said: “This stuff you’ve given me, I don’t know how it’s helping my mental case, but when I masturbate, I’m dry.” Amobi heard this story and he also discovered research from the early 1980s that there was another, very different drug with a similar side-effect: phenoxybenzamine, a medication for high-blood pressure. For some reason, these two treatments disrupted the so-called Mexican wave that a man experiences during sex to produce a “dry orgasm”.

All Amobi and his team had to do was to find other compounds that had the same effect on ejaculation without side-effects of their own (thioridazine caused drowsiness and phenoxybenzamine could lead to dizziness) and without affecting other muscles in the body. In news reports at the time, he suggested that this might take them five years.

Eight years on, Amobi’s male pill has not come to fruition – and in fact its only meaningful progress since 2006 has been a prototype test on rams. The stumbling blocks are recurring ones, at least in the world of male contraception. Despite all the publicity that research received, Amobi and his team have found it impossible to secure grants to develop the treatment. They are currently asking for around £200,000 and cannot even raise that. This is despite evidence that their pill could have benefits beyond contraception, most notably that it could reduce the transmission of HIV.

The non-hormonal Vasalgel, supported by Lissner, is essentially a reversible vasectomy whereby a polymer gel is injected into a man’s vas deferens (another injection flushes the gel out). Pioneered in India by an eccentric scientist called Sujoy Guha, it has been used – on humans – since 1989 and has been claimed to have been 100% successful to date. Lissner changed the name (it was formerly known as Risug) and her team tweaked the recipe, recently conducting experiments on rabbits. They recently started tests with baboons, and she hopes it could be available in 2016.

A recurring issue in clinical tests for a new male pill has been uncomfortable side-effects. So far, the majority of attempts to find a solution have been hormonal typically using some combination of progesterone, to inhibit a man’s sperm, and testosterone, to ensure he retains his inherent manliness. This has proved problematic, leading to mood changes, depression and weight gain – and also to an increased libido.

Hormonal trials have an extensive history of foundering, too. In 1997 a research team at Edinburgh Royal Infirmary, led by Dr Cameron Martin, embarked on final tests for a progesterone pill that were closely tracked in news-papers. Dr Martin predicted it would be available for men as early as the new century – obviously he was an optimist – but warned that we should never expect a silver bullet. “The male pill will have some side effects,” he reported. “It won’t be a wonder medicine.”

Right now there are three options for men who would rather not produce offspring – condoms, withdrawal and sterilisation — and none is exactly flawless. A vasectomy, although incredibly reliable, needs to be considered a permanent procedure, while withdrawal and condoms are both problematic. With perfect use, the failure rate of condoms is 2%, and that figure rises to 18% for couples who rely on them exclusively. According to estimates, there are 80m unintended pregnancies in the world each year, which is — by coincidence — the same figure as the global population increase.

The usual rejoinder is that men don’t want to take control of contraception, but that view is not reinforced by the studies. According to a 2005 survey of 9,000 men in four continents, 55% said they would be interested in a male pill or something similar. An increasingly prevalent factor in developed nations is that men are now financially responsible for any children they father.

Practitioners in the field have been pursuing a solution for decades — the leading experts are mostly at retirement age or beyond — and would be happy to see any of the rival methods cross the finish line. “If someone else came up with one first and got it to clinical trials or even to market, that would help everyone else. “Will it happen in our lifetime?” he ponders. “I wouldn’t outlay a lot of money on it, but I’m reasonably confident.”