Tuesday 4 December 2018

Hope for male 'pill' breakthrough after huge cash injection

Dundee University researchers receive $1m funding boost from Bill and Melinda Gates Foundation

Researchers at a Scottish university hope to make a breakthrough in the long hunt for a male pill, thanks to a grant of more than $900,000 that will allow them to screen thousands of existing drugs to see if they have potential.

The money comes from the Bill and Melinda Gates Foundation, which has been crusading on family planning for many years, with initiatives to help more women in developing countries access the contraception they want to control the size of their family.

It is now investing in research into a male pill, after global studies showing men in many countries would be willing to use it – if there were one.

Researchers at Dundee University have been given $929,585 (£728,311) over two years for work at their National Phenotypic Screening Centre. They are seeking existing drugs or chemical compounds that can interfere with certain sperm behaviours (phenotypes) essential for fertility.

Dr Paul Andrews, the director of operations, said: “Firstly, their ability to swim up the female reproductive tract and, secondly, a cellular process in the head of the sperm which must happen for the cell to progress towards the egg. Our screening efforts so far have shown such drugs exist.”

The hunt for a male contraceptive pill was launched in the 1950s, when the female pill was invented. Photograph: Getty Images/iStockphoto

News of the grant was revealed as a team in the US announced a trial of a more traditional approach – a hormonal gel. Men at three sites will use a gel that is absorbed through the skin on their upper arms and shoulders, containing the progestin hormone used for female contraception, and testosterone.

As early as the 1640s, there was a male contraceptive made out of animal intestines, which came with Latin instructions to wash in warm milk to avoid infections.

Though today’s condoms look a little different and are more widely available, the basic sperm-blocking concept is the same and it is the only reversible method of male contraception – unless you count withdrawal. The hunt for a male contraceptive pill has been going on without success since the 1950s, when the female pill was invented.

Apart from condoms, said Chris Barratt, a professor of reproductive medicine at Dundee’s School of Medicine, “the reality is we have vasectomy which is irreversible but there is nothing else for men”.

The traditional approach has been to try hormones and steroids to stop sperm production. But so far these have not worked well and there are side-effects, from weight gain to acne. “People have been more optimistic than they should have been and it has dominated the funding,” he said.

The constant disappointments have led to fewer attempts to find an answer. “The research that has been done on male contraception you could write on a postage stamp,” said Barratt.

Though there has long been the question of men’s willingness to use a contraceptive pill – and women’s willingness to trust them to use it – Barratt insisted attitudes had changed.

“People are moving away from feeling reproductive health is basically the woman’s problem,” he said. “Research from the World Health Organization has shown if there was a reversible male contraceptive pill available, men would take it.”

Andrews said their approach was novel in looking at the behaviour of sperm in infertile patients, who may have sperm that do not move or can swim but not penetrate the egg.

“There are profound defects that make them not move or there are defects in the head of the sperm,” he said. “We’re trying to find drugs to target and immobilise the sperm and stop it getting into the egg.

Melinda and Bill Gates. The billionaire philanthropists have been crusading on family planning for many years. Photograph: Reuters
“We’re sort of learning from the genetic defects out there. Unfortunately there’s not a lot known about the genetic causes of infertility. We’re taking a leaf out of nature’s playbook.”

The team will screen whatever drugs and compounds they can find that they think may interfere with the behaviour of sperm, such as a library of 13,000 compounds funded by Gates at the University of California, which has been a source for potential drugs against neglected tropical diseases. If they find nothing in California, their technology can screen “a plethora of other libraries”, Barratt said.

“I think at the end of two years we will have very good information if there are drugs currently on the market or in the pipeline that could be tweaked for contraception. If there are drugs, that will be fantastic.”

Meanwhile, a trial has begun in nine centres around the world – including Los Angeles, Seattle, Manchester and Edinburgh – of a gel that men can apply to their body, enabling hormones that will prevent sperm production.

It follows the trial of two injections every eight weeks, commissioned by the World Health Organization, which was successful at preventing pregnancies – but was halted in 2016 because the side-effects caused too many men to drop out. The problems included severe acne and mood swings.

This time, Dr Christina Chung-Lun Wang of the Los Angeles Biomedical Research Institute, who is leading the trial sponsored by the National Institute of Child Health, and co-led by the Population Council in the US, is hopeful men will be more comfortable with the gel.

Researchers will ask participants to complete questionnaires about their well-being before and after the trial. “The men’s sexual function must be maintained,” she said. “And last time, we were not tracking the mood swings prospectively.”

The man must spread 5ml of gel on his skin. “He puts it on both upper arms and shoulders. It dries quickly. But the instructions are that after application, he should not be in close skin contact with any other person,” she said.

The gel could be rubbed off on to someone else. He should shower a few hours afterwards and then he can have contact with family, partner or children. Or he can wear a T-shirt.”

They hope to have some answers in about a year. Researchers were working on a pill, she said, but it was currently not possible to get the required dose of testosterone into a single daily tablet. The challenges to a male contraceptive remain but the quest goes on.

(Source: The Guardian)

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