Sixty-four years after the first female contraceptive pill was approved for NHS use in the UK, science is finally on the verge of producing one for men.
Animal studies show the experimental tablet – currently known only as YCT-529 – could effectively switch off sperm production, and a recent trial with 16 healthy men found it did not cause serious side-effects.
The next step is studies on hundreds of men, to establish whether it is effective at preventing unwanted pregnancies. If successful, the world’s first male contraceptive pill could be available within three years.
The quest to find a male contraceptive pill has been a long one.
Most attempts have focused on methods that suppress the activity of hormones, called gonadotropins, which stimulate the production of sperm. But this can dampen libido and cause adverse effects, such as muscle weakness and hot flushes.
YCT-529 is generating excitement among fertility scientists because it does not rely on disrupting hormones in order to achieve birth control.
The Pill works by blocking the effects of a protein called retinoic acid receptor alpha, which plays a crucial role in sperm formation.
Richard Anderson, a professor of clinical reproductive science at Edinburgh University, said the male pill is generating ‘a lot of excitement and interest’
Instead, it works by blocking the effects of a protein called retinoic acid receptor alpha, or RAR-alpha, which plays a crucial role in sperm formation.
Retinoic acid is an important nutrient, which the body makes from vitamin A (in foods such as cheese, spinach and carrots).
It binds to RAR-alpha proteins, which are found on cells throughout the body – including the brain, liver, lungs and skin – where it helps with new cell growth.
For men, it plays a vital part in the production of new sperm. Without enough retinoic acid, sperm output is almost completely switched off.
YCT-529 works by docking with the RAR-alpha in the testes – blocking the entry of retinoic acid into cells which is needed to ensure healthy sperm production.
In tests, mice given the pill daily for four weeks experienced a dramatic decline in sperm counts – and it was 99 per cent effective in preventing pregnancy. The effects wore off four to six weeks after the drug was stopped, and the male mice were able to father offspring again.
A recent study by manufacturer, YourChoice Therapeutics, gave 16 men the daily tablets in doses ranging from 10mg up to 180mg for a month.
The findings showed that it was generally safe and well-tolerated, with no signs of it affecting libido, hormone balance or mood, reported the journal Communications Medicine.
‘This is good news,’ says Tet Yap, a professor of urology at King’s College London.
‘It looks like things are moving forward. The next step is to look at safety and effectiveness in larger groups of men.’
However, this male pill is no quick fix. It can take two months or more for sperm production to fully wind down – which means other forms of contraception may still be necessary during that period. And it takes another two to three months for sperm output to fully recover, should the man want to start a family.
There are also unanswered questions about the pill’s safety, says Professor Yap.
One is whether it only blocks retinoic acid in the testes, or also elsewhere in the body.
This is important because retinoic acid has many roles, one of which is to keep the immune system working properly.
‘A few of the volunteers suffered with respiratory tract infections during the trial, which begs the question, does the drug suppress the immune system?,’ says Professor Yap.
‘Plus, one volunteer complained of cardiac arrhythmia [an irregular heartbeat] while taking the drug. That could be completely random, but the trial was too small to tell us whether or not it was due to the drug.’
Richard Anderson, a professor of clinical reproductive science at Edinburgh University, said the male pill is generating ‘a lot of excitement and interest’.
He added: ‘In animal models the mechanism certainly looks plausible but it’s early days and there’s limited information so far on its effect in humans.’
Other research teams are investigating alternative approaches.
One is a gel injected into the sperm ducts to block the release of sperm into a man’s semen. Results released earlier this year by the company developing it showed the gel, called Adam, blocked sperm release for at least two years. However, the results have yet to be published in a peer-reviewed journal.
Another option is Nestorone – a gel that is rubbed on a man’s upper arms once a day and contains a combination of segesterone acetate (a synthetic female sex hormone that switches off sperm production) and the male hormone testosterone.
Although effective, the former can drive down natural testosterone levels, causing erectile dysfunction. The testosterone is added to the gel to counter this.
Hundreds of men have already taken part in international clinical trials for the gel and results presented at a medical conference in Boston last year showed it was an effective contraceptive in 86 per cent of men, after 15 weeks of daily use.
