Male contraceptive pill comes a step closer with vitamin A blockers

A US research team has tweaked some experimental compounds that show promise. Theirs is one of half a dozen male contraception methods, including some very hot baths, now being evaluated

PUBLISHED : Sunday, 13 March, 2016, 5:02pm
UPDATED : Sunday, 13 March, 2016, 5:02pm

The 20th century saw great strides in the development of birth control methods for women, but no new contraceptive for men has been approved since the introduction of the condom (first recorded descriptions in the 16th century) and vasectomy (in clinical practice since the late 19th century).

Could a male pill now be around the corner, however?

Researchers from the University of Minnesota in the United States suggest they’ve taken a step closer to formulating one by tweaking some experimental compounds that show promise. On March 13, the researchers presented their findings at the 251st National Meeting & Exposition of the American Chemical Society in San Diego. California.

There are many different experimental contraception methods being studied, but the Minnesota researchers’ focus is on inhibiting retinoic acid – commonly known as vitamin A – in the testes. Without vitamin A, testicles cannot make sperm.

Jillian Kyzer, a graduate student working on the topic, says the researchers are gaining a better understanding of how tweaks to the chemical structure of their test compounds (experimental male contraceptives developed by drug company Bristol-Myers Squibb) affect the substances’ cellular interactions in the body.

For instance, one of the test compounds is good at inhibiting fertility but isn’t very soluble, so it can’t be taken by mouth. “No one wants to inject themselves with a needle once a day or once a week for most of their lives,” notes Kyzer, whose colleagues have managed to refine the chemical structure of the test compound to make it more soluble.

Bringing any male contraceptive to market requires it to satisfy several requirements, explains Kyzer’s team leader, Professor Gunda Georg, head of Minnesota’s department of medicinal chemistry. It would have to be soluble so it could be taken by mouth. It would start working fairly quickly, and it wouldn’t diminish libido. It would be safe even if taken for decades. And because some users would eventually want to have children, its impact on fertility would be reversible, with no lingering ill effects on sperm or embryos.

“That’s a very high bar for bringing a male contraceptive to market,” Georg says.

According to Dr Paul Kogan and Dr Moshe Wald of the University of Iowa’s department of urology, research shows that condoms and vasectomies account for only 8.9 per cent of global contraceptive use.

“Surveys have demonstrated that nearly 80 per cent of men believe contraception is a shared responsibility and globally more than 50 per cent of men endorsed interest in an alternative male contraceptive,” write Kogan and Wald in a 2014 report in the journal Urologic Clinics of North America. “These studies demonstrate an unmet need for alternative male contraception.”

Georg started working on developing a viable male birth control pill in 2001. In 2013, her team received a US$8.3 million, five-year contract from the US National Institute of Child Health and Human Development of the National Institutes of Health to develop new male and female non-hormonal birth control targets and expand on current targets.

With female birth control you only have to control one egg. In males you have to control millions of sperm – about 1,500 sperm are produced every second. Georg thinks that may be part of the reason why a male pill has been so difficult to develop.

Significant developments, however, have been made with regard to hormonal and non-hormonal contraception, and minor, reversible, procedural contraception. Here’s a look at some alternative methods of birth control for men.

Vasalgel

How it works: similar to a no-scalpel vasectomy, except a gel is injected into the vas deferens (the tube sperm swim through after being produced in the testes), rather than cutting the vas deferens as is done in a vasectomy. Vasalgel fills the interior of the vas deferens, forming a soft, semi-permeable barrier for the sperm. The sperm end up being reabsorbed by the body.

Effectiveness and safety: Twelve months of rabbit studies have shown no sperm from the second semen sample onwards. Sperm flow quickly returned in rabbits that had the polymer flushed out with another injection. Clinical trials are expected to begin this year. Vasalgel was inspired by the work on a polymer contraceptive called RISUG, which is in advanced clinical trials in India; some of the men have been using RISUG for more than 15 years.

Reversible? Possibly.

Clean sheets pill

How it works: this method is so named because it inhibits the release of any semen, while allowing the sensation of orgasm. It acts by relaxing the longitudinal muscles in the vas deferens while still allowing contraction of the circular muscles, which squeeze the tubes carrying the sperm and semen – effectively cutting off the flow. The fluids remain where they are and are reabsorbed by the body naturally. This method is extremely fast-acting, with the pill needing to be taken only two to three hours before intercourse. Its effects would then last 16-24 hours.

Effectiveness and safety: the drug the pill is based on, phenoxybenzamine, has some side effects. But the prototype contraceptive pills have been designed to avoid these effects and isolate its muscle-relaxing function. However, the research is still in its early stages.

Reversible? Unknown.

Ultrasound

How it works: using the same painless ultrasound waves commonly used by physical therapists on injured joints, applying ultrasound for 15 minutes to the testes results in about six months of contraception in animals (dogs and rats) due to decreased sperm count.

Effectiveness and safety: while ultrasound works in dogs and rats under the right conditions and protocol, scientists have yet to find a way to get long-lasting effects in large adult monkeys and humans. In 2013, a man tried ultrasound on himself and found the effect wearing off within a few months, despite completing at least 10 treatments of 20-30 minutes on a Monday-Wednesday-Friday schedule.

Reversible? Possibly.

Gendarussa

How it works: derived from the Justicia gendarussa plant, a three-metre high shrub that is native to Indonesia, this herbal contraceptive is said to disrupt an enzyme in the sperm head, which weakens the ability of the sperm to penetrate the ovum.

Effectiveness and safety: phase 2 clinical trials provide convincing evidence of its effectiveness. For example, a 2010 study had 80 of 120 married men take the extract for 102 days. In 2012, another study had 186 of 350 married men take the pill for 30 days. Only one pregnancy occurred during the trials. Preliminary findings have not shown any side effects; more research is needed to determine the pill’s duration of action and dosage.

Reversible? Yes.

Heat

How it works: heat’s action on fertility is not completely understood, but part of the effect seems to be due to a heat shock factor that initiates cell death in sperm above about 35 degrees Celsius. The testes must be several degrees cooler than normal body temperature in order to maintain proper sperm production. A simple wet heat method was reported in 1946 by Dr M. Voegeli, a Swiss doctor practising in India. She suggested: “A man sits in a [shallow or testes-only] bath of 46.7 deg Celsius for 45 minutes daily for three weeks. Six months of sterility results, after which normal fertility returns. For longer sterility, the treatment is repeated.”

Effectiveness and safety: Water at 46.7 Celsius was found to reliably produce at least six months of sterility. Water at lower temperatures produced shorter periods of infertility; for example, water at 43.3 Celsius produced at least four months of infertility.

Reversible? May not be possible after long-term use.