Major breakthrough in hormone-free male contraceptive pill research

Researchers in an Australian lab have taken a major step forward in the development of hormone-free male contraceptive pills.

Australian researchers have made a major advancement in developing hormone-free male contraceptive pills.

The development has been made by scientists at Monash University, and involves 3D mapping of a key bodily protein.

The researchers involved said the imaging of the protein had been “the main stumbling block” in developing a contraceptive pill that did not interfere with the long-term viability of sperm or sexual and general health.

“Unfortunately, there has been a widespread perception that birth control is a women’s problem rather than a men’s problem – we hope to change that,” said senior author of the study, Sab Ventura.

The researchers hope to help in the development of non-hormonal male contraceptive pills, rebalancing the burden of birth control. Picture: iStock

Dr Ventura has been leading the Monash Institute of Pharmaceutical Sciences’ male contraceptive program for more than two decades.

“Our primary goal is to develop a male contraceptive pill that is not only hormone free but also bypasses side-effects such as long-term irreversible impacts on fertility and, thus, making it suitable for young men seeking contraceptive options,” Dr Ventura said.

This latest breakthrough has been published in Nature Communications, with the article titled “Structural insights into the human P2X1 receptor and ligand interactions”.

In previous studies, the Monash University researchers have shown male infertility can be genetically achieved by simultaneously deleting two proteins that trigger the transport of sperm – α1A-adrenergic receptor and P2X1-purinergic receptor (P2X1) – but without affecting the long-term viability of sperm or sexual and general health.

But the chemical biology of the P2X1 receptor was not fully known.

Targeting the receptor had been like “throwing darts at a dartboard hoping for success”, Dr Venture said.

Unintended pregnancies place a large burden on the health system. Picture: iStock

The researchers used cryo‐electron microscopy to determine the 3D structure of the receptor; this will allow a more focused and accurate drug to be designed.

Drugs that target the other key receptor – the α1A-adrenergic receptor – are already in use, but zeroing in on P2X1 has been more difficult.

“Now we know what our therapeutic target looks like, we can generate drugs that can bind to it appropriately, which totally changes the game,” Dr Venture said.

Senior author Associate Professor David Thal said cryo‐electron microscopy had been revolutionary to drug discovery, as it showed the 3D structure of molecules previously too difficult to observe.

Condoms have been around for more than 300 years, but hormone-free male contraceptive pills are still a work in progress. Picture: iStock

“By tapping into this state-of-the-art technology we’ve been able to describe the first ever high-resolution structure of P2X1, opening up an exciting new suite of opportunities for developing drugs to target this receptor,” he said.

This month, the NSW government made the contraceptive pill available at pharmacies rather than requiring women to go to the GP.

A 2020 study found that in 141 countries, higher fertility rates – the average number of children that are born to a woman over her lifetime – correlate with lower female education levels and GDP.

A widely cited 2009 study says worldwide 38 per cent of pregnancies annually are unintended, and 22 per cent end in abortion.

In the US, in 2002, 12 million unintended pregnancies were prevented, directly saving $19bn in medical costs, the study found.