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27 May 2016

What male contraceptives are scientists working on? And how soon can we use them?

The male Pill, the male coil, and a medication made from papaya seeds. 

By Zayani Bhatt

When you think about it, male contraception makes more logical sense than female contraception: to put it bluntly, it’s safer to unload a gun than to shoot at a bullet-proof vest. 

Yet scientists have found it harder – or have been more reluctant – to control a million sperm a day than a single egg a month, and so there are, to date, ten different types of contraception available for women and only two (condoms and vasectomy) currently available for men.

This places a tremendous amount of pressure on women to avoid pregnancy. But it’s not just women calling for more options for their partners: men are demanding more control over their reproductive ability, too. A study published in the journal Human Reproduction indicated that around half of men would be open to using a male contraceptive, while three in eight wanted to know more information first.

Aaron Hamlin, executive director of the Male Contraceptive Initiative, tells me that this may be an underestimate: “[The researchers] asked about a hormonal contraceptive. Had the survey asked about a non-hormonal contraceptive, the acceptability may have been even higher due to the lower likelihood of side effects and potentially faster onset of action.” Hamlin is very clear that “contraception isn’t an either/or equation between men and women”, but its development for men has been slowed by a lack of funding:  

“Drug development is expensive. And if governments and philanthropists are interested in people being able to control their family sizes and futures, then they need to start taking funding for male contraceptive development seriously. The pill for women was funded practically single-handedly by philanthropist Katharine McCormick.  So far, there has been no modern-day Katharine McCormick for the male pill.”

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There are, however, many male contraceptive options in the works. So what are they? And when will they be available?

On the way soon

Vasalgel: a sperm barrier

What is it? A hydrogel, which is a network of polymers suspended in a water-based gel. They’re quite flexible; much like the body’s natural tissue.

How does it work? Sperm are produced in the testes and then transported through a duct called the vas deferens. Vasalgel is injected into this duct, where it creates a semi-permeable barrier that allows fluid through, but not sperm. Vasalgel is reversible and works for up to a year, after which sperm flow returns almost immediately, or it can be removed by another injection that simply flushes it out of the system.

How soon can we use it?  Human trials are due to begin at the end of 2016 and men should be able to get the injection by 2018. Rights for the gel are owned by the non-profit organisation Parsemus Foundation which was started by Elaine Lissner, who while at Stanford University became frustrated by the almost-exclusive pressure on women to sort out contraception.

The male Pill

How does it work? This contraceptive is, rather amusingly, known as the “clean-sheets” pill for its ability to prevent fluid ejaculation. The pill relaxes the longitudinal muscles of the vas deferens whilst still allowing contraction of its circular muscles. This stops the sperm from being pushed out, but still allows orgasmic function. The blocking of fluid ejaculate also helps prevent the spread of some STIs.

How soon can we use it? The side effects of the major component of the drug, phenoxybenzamine, currently include dizziness, drowsiness, nasal congestion, stomach upset and tiredness. (It’s worth noting though that these are all common side effects of the pill for women.) However, researchers at King’s College London and University College London have created a prototype that evades these problems and together, they are now seeking funding to start trials of the pill on rams.

Intra Vas Device (IVD): the male coil

What is it? Like an inter-uterine device (IUD), or coil, for women, IVDs are inserted into the men’s vas deferens and block sperm from moving down into the ejaculate.

How does it work? There are two types in development. The first, made in the US, involves inserting two sets of tiny, flexible silicone plugs into each vas deferens so that there is a space between the two plugs for the sperm to store. Researchers say the plugs can’t be felt by the patient, and the procedure is effectively like getting a vasectomy, but without cutting your tubes. 

The second, developed in China, is a flexible urethane tube with one end closed which is implanted into each vas deferens. Each tube is lined with a nylon mesh that acts as a sieve to collect sperm. A tiny hole at the closed end of the tube allows fluid, but not sperm to pass through, preventing the build-up of pressure that is often associated with a vasectomy.

Both procedures don’t require a scalpel and take less than twenty minutes to perform under general anesthetic. There are lower levels of side-effects compared to a vasectomy too, and reversal is thought to be a fast, out-patient procedure.

How far is it in development? Both types of IVD are currently undergoing human trials, which means they could be available within the next several years.  

On the horizon

Herbal contraception

What is it? Researchers in Indonesia have managed to isolate the active ingredient in a shrub called Gendarussa to make a contraceptive pill. Local tribesmen and villagers on the island of Papua have been boiling the plant and drinking it as a tea half an hour before sex for generations now.

How does it work? Upon contact with an egg, sperm secrete an enzyme that allows them to break through the surface. Scientists at the Airlangga University in Indonesia have discovered that this plant is able to inhibit this enzyme whilst not affecting sperm count, mobility or sexual pleasure.

How soon can we use it?  The pills have just passed Phase II of clinical trials and following a third, the drug could go onto the market in Indonesia. To reach the UK, however, the pill would need to undergo more clinical trials to meet our health test standards.

Heat, part one 

What is it? We all learned in school biology lessons that the testes rest at a cooler temperature than the rest of the body in order to allow sperm production. Logically then, it follows that increasing the temperature of them will lower if not stop sperm production.

How does it work? Known as “wet heat”, this method was first investigated in 1946 by Dr Marthe Voegeli in India in a study with only nine volunteers. Keeping the testes in a testes-only bath for 45 minutes daily for three weeks resulted in six months of sterility. The tests’ success meant that the practice was used widely during a famine in India and children born after it had no abnormalities. It is easily reversible, can be used multiple times and is non-surgical. However, Voegeli’s conclusions were never taken seriously at the time, in part because she was a woman.

How soon can we use it?  It is now being explored as an option of “booster” contraception for men. Hot packs, heating pads and over-the-counter fertility packs to check sperm count are now becoming available.

Heat, part two

How does it work? The second option, Cryptorchidism, mimics “Cryptorchid”, or the condition of undescended testicles. Both the testes and their temperature are raised by a pair of underwear that contains a ring which hoists the testes up close to the canal through which they ascend in Cryptorchid. This increases their temperature through their proximity to the body, and the soft ring of material holding them in place reduces fertility and the sperm’s mobility. This is a reversible method that allows for the return of fertility in twelve to eighteen months.

How soon can we use it?  So far, only short term tests of one to four years have been conducted. Longer-term tests on a larger scale would show whether men who still want to have children in later life can do so after the treatment or not. Scientists are also worried that the treatment could increase the risk of testicular cancer.

Carica Papaya: the seed contraceptive

What is it? Seeds of a carica papaya haven been commonly eaten by men for many a generation in parts of South East Asia.

How soon can we use it? In the first study conducted on this, an extract of papaya seeds was fed to rats, resulting in decreased semen and a one hundred per cent efficacy, but with less than ideal side effects – due to the extract’s toxicity, the rats experienced dramatic weight loss. A chloroform extract of seeds tested on monkeys, however, caused low sperm production, no toxicity, no change in testosterone levels and full recovery within five months. If human trials go as well, we might soon start seeing men on the tube scoffing papaya seeds.

A bit of a pipe dream

Ultrasound

How does it work? Scientists believe ultrasound could be used to reduce men’s fertility temporarily, but they’ve yet to make it work in humans. The Parsemus Foundation funded a study on it on humans at the University of North Carolina and another in Italy on the sterilisation of dogs with ultrasound.

It was found that simply three applications for five minutes each with breaks of 48 minutes rendered dogs permanently sterile. Only one man was tested on and he found that even after exposure to ultrasound for ten days for twenty to thirty minutes, his fertility returned after just a few months.

How soon can we use it? Funding of this method has dried up given the poor results so far, though ultrasound is readily available online for men who wish to try it themselves (a science background is recommended though) and in doctor’s and physical therapist’s offices around the world.

Neem: the tree contraceptive

What is it? The Neem tree is native to India and was used as a male contraceptive in ancient times.

How does it work? For long-term contraception, a small amount of Neem oil injected into the vas deferens seems to provide eight months of contraception with no change in testosterone levels. In the 1980s it was found that Neem leaf tablets provided reversible male infertility but with no change in sperm production or libido in monkeys.

How far is it in development? Further study is still needed. Men in many rural parts of India however, continue to take the herb, apparently with the desired effects.

Adjudin/Gamandazole: derivatives anti-cancer medication 

What is it? Lonidamine, an anticancer medication, was found to cause infertility but at the expense of kidney damage at high doses. Scientists searching for a drug similar to Lonidamine discovered Adjudin and Gamandazole.

How does it work? In New York, a non-profit called the Population Council dedicated to finding more options for male contraception, discovered that Adjudin disrupts the process of sperm maturation in the testes by blocking the hormone that enables this and researchers at the University of Kansas Medical Centre found that Gamandazole does the same by preventing the sperm from developing its head and tail.

How soon can we use it? Adjudin researchers are still trying to find ways to improve its delivery into the body while Gamendazole, although promising, still has to undergo human testing and it will be several years before it’s available at the doctor’s office. 

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