© Renaud Vigourt at Heart Agency

“We’re talking about drugs men are going to take for a really long time, so the pathway for approval is long too,” says contraception researcher Diana Blithe. “So when scientists say, ‘I have a product in mice that looks promising, we’ll have a drug in five years,’ it’s very unrealistic.” Nevertheless, she admits to being “really excited” about the approaches she’s supporting.

Blithe is director of the male contraceptive development programme at the US National Institute of Child Health and Human Development (NICHD) in Bethesda, Maryland. She’s responsible for one of the largest pots of male pill research money available today and believes a hormonal method is most likely to do the job.

She points out that American men can already buy testosterone gels that could form part of a male contraceptive, and which show how to get a male hormone product approved. Adverts everywhere in the USA talk about “low-T” – low testosterone levels – and the gels men can rub into their skin to treat them. Similarly, NICHD funds researchers at the University of California, Los Angeles and the University of Washington to do clinical trials using testosterone and progestogen in gels.

Would men take a pill? We think they will

NICHD is also closing in on an elusive pill-form male hormonal contraceptive. Forms of testosterone that we can absorb from our stomach and gut rapidly break down in the body, meaning men would have to take pills three times a day. “Would men take a pill?” Blithe asks. “We think they will – but not every eight hours.” Therefore NICHD has developed a hormone that does the job of both progestogen and testosterone and only needs to be taken once a day. This too is moving into clinical trials.

Although she’s enthusiastic about these ideas, Blithe stresses that NICHD can’t do what Coelingh Bennink wants them to, and take male products through to approval independently. Instead, she and her colleagues are continuing to seek involvement from drug makers. “Our hope is to show that it works well and men like it, and then a pharmaceutical company will recognise that it’s safe,” she says. “We are doing phase II now on the gels and if it works really well and we still don’t have a partner, I don’t know what the Institute’s decision will be, whether they will want to continue.”

While scientists can work on how hormonal drugs are taken and their side-effects, one downside seems unavoidable. It takes one to four months to clear out already-made sperm and achieve the contraceptive effect, and a similar period for fertility to return. NICHD is therefore also backing research on non-hormonal methods that might be effective more quickly, but Blithe admits these are “way further back” in animal testing.

If NICHD worked in the UK, they might therefore be interested in Nnaemeka Amobi from King’s College London’s non-hormonal ‘instant male pill’. Also known as the ‘dry orgasm pill’, Amobi’s contraceptive stops men releasing semen and the sperm it contains. He stresses that otherwise the normal physical processes involved in a man’s orgasm are unaffected.

“The movement of semen from the testes to where it stays until you have the projectile phase of emission, called ejaculation, happens long before climax,” Amobi says. “As soon as you’re aroused, spermatic fluid is moved towards the seminal vesicles and prostate. Our pill stops that initial movement by inactivating the tubes that propel fluid from the testes to the prostate.”

Amobi and his fellow researchers started from two existing drugs that had caused dry orgasms as an undesirable side-effect. They redesigned the drugs to remove the original intended actions and focus on this. Animal tests suggest that they have succeeded. “We used rams because rats and rabbits don’t have seminal fluid like humans,” Amobi says. “We tried boars, and boars produce 250 millilitres of semen. Can you imagine that? Rams have 1 millilitre, closer to humans’ 2–5 millilitres.”

These tests show the method could become effective within 3–4 hours, and wear off after a day. “A woman can say, ‘Here’s the pill – let me see you take it’,” Amobi says. And as well as avoiding pregnancy, preventing semen emission should help reduce sexual transmission of semen-borne diseases, such as HIV.

One potential backer interested in the drug was the Parsemus Foundation, a small private organisation based in Berkeley, California. Ultimately, though, its founder Elaine Lissner faced a tough choice between funding Amobi’s research and another promising new male contraceptive technology. She chose to spend the foundation’s little cash on the latter. Amobi isn’t bitter because, in his opinion, Lissner is the main reason people still talk about male contraception. But she still has regrets. “It’s shocking that they can’t get backing for the first new idea about HIV transmission prevention in ages.”

Having started the Parsemus Foundation in 2005 with a little of her own money, Lissner has a personal relationship with how it’s spent. In contrast to Blithe, she dislikes hormonal approaches because of their side-effects, and she also dislikes risk. Parsemus has therefore adopted an approach similar to one already tested in men, in India. But it’s not a pill – it’s a ‘hydrogel’ injected into the vas deferens, the tube linking the epididymis to the penis.

People are crazy for Vasalgel, desperate for it

Called Vasalgel, it lets through semen but not sperm, and is intended to be washed out by another injection when men want the use of their sperm back. The blocked sperm are cleared from the epididymis and eaten up by immune cells, as happens normally if a man hasn’t had an orgasm for a while. Lissner publicises Vasalgel energetically, and one glance at its thriving Facebook page should dispel any doubts that men would be interested. “People are crazy for Vasalgel, desperate for it,” she says. “We have over 32,000 people on the mailing list waiting to hear about clinical trials.”

One man who’s keen to try it is Justin Terry, a married 30-year-old machinist who makes vehicle parts in Alabama. He and his wife don’t have children, and his wife is taking the contraceptive pill. “We’ve been married ten years,” Justin says. “She doesn’t want kids and neither do I, really. She wants to get off the pill.” The pill gives his wife tender breasts, and she is concerned about adverse effects of continuing to take it. As with hormonal approaches, his sperm would still flow for weeks after Vasalgel is injected, but this doesn’t bother Justin. He has considered vasectomy, as have I, but has hesitated in part because it’s not completely reversible. “Vasalgel sounds like it will be reversible and would involve much less invasive surgery,” he says.

Parsemus’s efforts have been helped by the David and Lucile Packard Foundation, also based in California, which provided $50,000 to help them test the approach in baboons. “We expected to be out of money last year and we’re not,” Lissner says. “But the clinical trial is half a million dollars, so that’s a different scale, and beyond that it’s multimillions.” The trial will involve about 30 men and will test Vasalgel as a vasectomy alternative, without looking at reversibility.

Knowing the field’s status, Lissner is not relying on government or the pharmaceutical industry. Instead, she’s looking for backing from wealthy ‘social investors’ – and of course potential end users – and is publicising what might be possible in the field to bring interested parties together. “The difference is that we have built an infrastructure where the public is able to channel its support,” she says.