Male birth control: The world’s been waiting for it. India may be the first to offer it. - Vox.com

Roughly half of all pregnancies^[1] worldwide aren’t planned. We can attribute this, at least partially, to the fact that half the species (ahem, women) bears most of the birth control burden. If men had access to a long-lasting contraception, researchers have projected, the rate of unplanned pregnancies would tumble^[2].

Now, Indian scientists claim they are getting closer to giving men such an option. Officials at the Indian Council of Medical Research say they’ve successfully completed clinical testing of the world’s first injectable male contraceptive, the Hindustan Times^[3] reported.

“The product is ready, with only regulatory approvals pending with [India’s drug regulator],” Radhey Shyam Sharma, a New Delhi reproductive biologist who leads the research, told the newspaper. “The product can safely be called the world’s first male contraceptive.”

If that were true, it would mean India has found one of the holy grails of reproductive medicine — overcoming the biological and regulatory challenges^[4] that have thwarted past attempts to bring a new male birth control to market. (For more on those, and other promising male birth control options, see here^[5].)

The product is a nonsurgical vasectomy called RISUG^[6], which stands for “reversible inhibition of sperm under guidance,” and it’s effectively an injection in men’s penises. If that sounds like something no man would ever agree to, let me explain.

With RISUG, doctors inject a polymer gel into the vas deferens, the tube that transports sperm and semen out of the penis, under local anesthesia. This is intended to block sperm, and therefore, the chances that a man impregnates a woman, with effects that can last for 13 years, Sharma told the Hindustan Times.

In some ways, it’s similar to a vasectomy, a surgery that involves cutting or tying the vas deferens to stop sperm from entering the urethra and getting passed along to a female partner. But reversing a vasectomy requires more surgery, and the RISUG treatment can reportedly be reversed simply with another shot that breaks down the gel and could cost as little as $10^[7].

RISUG’s potential has been highlighted by the media for years. In 2015, Vice^[8] called it “the perfect male birth control. ... It’s affordable, minimally invasive, and fully reversible—and it’s the most effective, non-permanent way of preventing pregnancy (from the sperm side) the world has ever seen, according to studies so far.”

A 2017 Bloomberg^[9] feature on the efforts to develop it suggested that it would get approval by Indian regulators that year. “The procedure is 98 percent effective at preventing pregnancy — about the same as condoms^[10] if they are used every time — and has no major side effects,” Bloomberg said.

But however promising RISUG may seem, and however much the world needs a new form of male birth control, some researchers are skeptical. And a closer look at the most recent phase three clinical trial of the treatment in India suggests there’s good reason to be cautious.

A new RISUG trial raises more questions than answers

Sharma recently published the results of the clinical trial^[11] on RISUG in the Indian Journal of Medical Research, and it tells a slightly more complicated story than what he’s been telling the press. The study involved 139 men under the age of 41 who were living with their wives and had at least two children each. The men were given a single dose of RISUG and then followed up by doctors for six months. Their wives were also monitored to find out if they became pregnant. Note: This is a small, short-term study.

Importantly, the partners of the 133 men in the trial who got the shot didn’t get pregnant despite having unprotected sex.

But while the researchers recorded no severe side effects, they did note that “mild scrotal enlargement” was common, as was scrotal pain and nodules at the injection site. These issues resolved within the six-month study period — but two men experienced ongoing “fluid collection” around their scrotums.

The short-term swelling and discomfort may be acceptable to men and regulators, since it resolved quickly, said Michael Skinner^[12], a reproductive biologist who studies male contraceptives at Washington State University. But the continued fluid buildup two men experienced is more concerning, and we’d need a longer-term trial to understand the impact of this response.

Even more curious, six of the men in the trial couldn’t tolerate a complete dose of RISUG “either because of leakage from the syringe or because of vas counter punctures,” the study’s authors wrote. The 133 men who did tolerate the shot only stopped releasing sperm between one and six months after the procedure, meaning the injection took a while to kick in. And while the partners of those men didn’t become pregnant, it’s not clear whether the sperm-fighting effects will last — and whether they will outweigh the potential harms of RISUG, since, again, the study was too small and short term to say for sure.

To reach the US market, regulators would need studies involving thousands of participants, explained Stephanie Page^[13], a professor of medicine at the University of Washington. The RISUG developer would also need to show that the treatment is as safe and effective as currently available birth control options.

But that might be difficult, Page said. “[RISUG] is a non-scalpel vasectomy that fails in six of 139 men. That isn’t great compared to vasectomy. And the ‘[switch] on rate’ is longer than a regular vasectomy, which is usually one month.”

A Berkeley, California-based non-profit called the Parsemus Foundation has licensed the RISUG technology in the US. And the related product they’ve developed, Vasalgel^[14], is only in the preclinical phase of testing. According to Parsemus, the results from animal studies — on rabbits^[15] and monkeys^[16] — are promising. But there’s no human trial scheduled yet. So despite the hype^[17], it’s also far from being approved for the market.

Even so, the Hindustan Times report said, it could be a matter of months before the product hits the Indian market.

We need more data to understand the effects of penis injection birth control

Before this new RISUG clinical trial was published, researchers have been raising concerns about the treatment. In 2014, researchers in India penned a commentary in the Indian Journal of Medical Research^[18] on RISUG’s promise and perils. “RISUG has surely created a new concept of contraception with great feasibility and long lasting sterility,” they wrote. “Unfortunately, the advancement of this injectable polymer is slow, the clinical trials are not providing enough robust conclusions.” (The lead author on that paper did not respond to Vox’s request for comment, nor did Sharma.)

A 2018 paper^[19] by researchers at the University of Virginia School similarly raised concerns about RISUG’s safety. They cited earlier stage clinical trials and studies in animals that showed RISUG may damage sperm and tissues in the male reproductive organs. “To date,” they also noted, “there has been no data reported on reversibility of RISUG in humans.” So only animal trials have demonstrated the product’s potential to be reversed.

Skinner^[20], the reproductive biologist, echoed these concerns. “I have not seen any large clinical trails yet, nor studies on reversibility in humans, so [we] will need to wait and see how useful it becomes,” he told Vox. “It could replace need for vasectomy in future, and if reversible [be] useful for contraception. The key is some large scale trials for utility and reversibility in humans.”

So for now, it’s probably best to ignore the hype until the slow grind of science yields clearer answers about RISUG.

References

1. ^{^} half of all pregnancies (www.ncbi.nlm.nih.gov)
2. ^{^} rate of unplanned pregnancies would tumble (https://ift.tt/1B6q9zl)
3. ^{^} Hindustan Times (www.hindustantimes.com)
4. ^{^} biological and regulatory challenges (www.vox.com)
5. ^{^} see here (www.vox.com)
6. ^{^} RISUG (en.wikipedia.org)
7. ^{^} could cost as little as $10 (www.bloomberg.com)
8. ^{^} Vice (www.vice.com)
9. ^{^} Bloomberg (www.bloomberg.com)
10. ^{^} condoms (https://ift.tt/o7wEXr)
11. ^{^} clinical trial (www.ncbi.nlm.nih.gov)
12. ^{^} Michael Skinner (skinner.wsu.edu)
13. ^{^} Stephanie Page (depts.washington.edu)
14. ^{^} Vasalgel (www.parsemus.org)
15. ^{^} rabbits (www.ncbi.nlm.nih.gov)
16. ^{^} monkeys (bacandrology.biomedcentral.com)
17. ^{^} despite the hype (www.vox.com)
18. ^{^} Indian Journal of Medical Research (www.ncbi.nlm.nih.gov)
19. ^{^} 2018 paper (www.ncbi.nlm.nih.gov)
20. ^{^} Skinner (skinner.wsu.edu)