How the Male Birth-control Pill Will Work

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Introduction to How the Male Birth-control Pill Will Work

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In 1960, an invention revolutionized female sexuality and paved the way for the women's liberation movement. It was the birth-control pill, or simply "the pill" as it became popularly known. An estimated 18 million women in the United States use the birth-control pill today, making it the most popular form of reversible birth control in the country.

For four decades, the pill has put women primarily in the contraceptive driver's seat. But an increasing number of people -- both men and women -- want men to take a more active role in contraception use.

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Condoms are one of the few birth-control options available to men today.

Their wish may be granted in the foreseeable future, as research companies grow closer to revealing the first continuous, reversible male contraceptive pill.

In this article, we'll give you a sneak peak at the male pill, find out how it will work and explore whether it is poised to trigger a revolution of its own.

For the past four decades, women have a wide array of birth-control options available to them, including the pill, ring, patch and injection, that are all more than 99 percent effective. Yet as far as science has progressed with female birth control, there are still only a couple of birth-control options available to men: primarily the condom and vasectomy. Some men complain that the former reduces sensation during intercourse, and others wince at the thought of the surgical procedure that the second requires (not to mention the second surgical procedure required if they decide they want to reverse it).

Why has it taken researchers more than 40 years to come up with a male equivalent of the birth-control pill? One reason is that pharmaceutical companies haven't had much interest in -- and more importantly, haven't had much research funding for -- a male birth-control pill.

Thank You Thank you to Craig C. Freudenrich, Ph.D., for his assistance with this article.

The other reason stems from inherent differences in male and female anatomy. The female birth-control pill contains synthetic forms of the hormones estrogen and progesterone, which prevent the ovaries from releasing an egg for fertilization. But unlike women, who release just one egg a month during a regular process of ovulation (see How Menstruation Works to learn more), men release about 120 million sperm with each ejaculation. It's a lot harder to control millions and millions of sperm than it is to control a single egg.

So how are researchers trying to tackle this biological issue?

How Will the Male Pill Work?

The ideal male birth-control pill would eliminate or block the majority of sperm a man produces without causing significant side effects or affecting a man's masculinity or sexuality.

Testosterone molecule

One of the main avenues for male birth control is the hormonally-based pill. And one of the main hormonal ingredients under investigation is testosterone, which is responsible for the development of sexual characteristics, including muscle mass and facial hair growth, in men. It is also responsible for sperm production in the testes. This is how the normal process works:

Giving a man extra testosterone can essentially shut down sperm production. Normally, at the start of the sperm-production cycle, the hypothalamus in the brain releases gonadotropin-releasing hormone (GnRH), which triggers the release of fertility hormones called gonadotropins (FSH and ICSH) from the pituitary gland. ICSH signals the testes to produce testosterone, and FSH and testosterone tell the testes to produce sperm. When sperm production is complete, the testes release testosterone and a hormone called inhibin into the body, which tells the brain that there's enough sperm. This stops the release of sperm-producing hormones. Then, the cycle begins again.

But if there are always high doses of testosterone in the bloodstream, they continually tell the brain that the testes are producing enough sperm, which shuts off the release of GnRH indefinitely. The trouble with this method is that giving a man the amount of testosterone necessary to suppress sperm production can cause several unwanted side effects, including acne, weight gain, prostate-gland growth and abnormal liver function.

Drawback One problem with a hormonal approach to contraception in men is that it would take several months for the birth-control protection to take full effect.

A more promising alternative uses a combination of testosterone and another sex hormone: progestogen (progesterone). In low doses, progestogen suppresses the reproductive hormone system of both men and women -- progestogen is a component of the female birth-control pill. In men, it inhibits sperm production in the testes. The drawback is that it can also affect male sexuality and sexual characteristics, so men who take progestogen must also have testosterone injections to maintain those characteristics.

Theoretically, the male "pill" would contain both progestogen and testosterone. But because digestion breaks down testosterone, a combination pill couldn't hold enough testosterone to be effective at reversing the effects of the progestogen. So researchers are conducting studies with a progestogen implant combined with testosterone injections (see Beyond the Pill).

Non-hormonal Pills

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Fertilized egg

Because of the challenges of creating a hormonally-based male birth-control pill, researchers are looking into non-hormonal methods to lower sperm count or somehow disable the sperm so that they cannot fertilize an egg.

Progress in the latter method was announced by researchers at the University of Massachusetts in 2005. Their idea is to inactivate the tails that enable sperm to swim to the egg and fertilize it. When sperm form in the testes, they have their tails but they cannot yet move them. It's not until the sperm pass through the epididymis (the long, coiled tube that connects the testis to the vas deferens) that they are able to swim. Researchers have discovered that a protein, called Cs, "turns on" the sperm's tails on their journey through the epididymis.

The idea is to use a biochemical messenger to block this protein, leaving the sperm unable to swim but otherwise healthy. Animal studies so far have been promising. And unlike hormonal birth control, this technique poses little risk of side effects. Researchers now need to find the right messenger to achieve this task in human males.

Another form of male birth control targets the immune system. A protein called eppin, which is produced in the testes and epididymis, facilitates sperm maturation. Scientists at the University of Washington have been able to immunize monkeys against eppin. Monkeys that developed an immune response against eppin became infertile, and when they stopped receiving the vaccine injections, they regained their fertility.

Researchers are also looking at drugs that stop sperm production as an unintended side effect, such the cancer medication lonidamine. Although lonidamine is risky because it can have toxic side effects on the liver and kidneys, there are similar drugs that look more promising.

Beyond the Pill

Whether the male pill will actually be a "pill" is up in the air. Tests so far on men have also been conducted with an injection or an implant version of hormonally-based birth control.

Photo courtesy N.V. Organon
Pharmaceutical company Organon is developing a male birth-control "pill" that is a combination of an implant and an injection.

Researchers from the pharmaceutical companies Organon and Schering AG are conducting a major study on a male contraceptive implant. In 2002, they began phase II clinical trials of a male birth-control implant containing the progestogen etonogestrel -- a hormone also present in hormonally-based contraception for women. The rods, which are implanted under the skin of the man's arm, are designed to remain in the skin for about three years, but they can be removed at any time. Because etonogestrel blocks testosterone as well as sperm production, men who get this implant will also need to receive testosterone injections every four to six weeks. The phase II trial finished in December 2005. The companies will announce in fall 2006 if they will begin phase II trials -- the last stage before the implant goes onto the market.

At the same time, researchers from the Population Council are developing implant, gel and patch versions of the synthetic hormone MENT® for contraceptive use.

The Future of the Male Birth-control Pill

If a male birth-control pill does become a reality, two big questions surround its possible use:

Will men take it?
Will women trust them to take it?

Studies so far indicate that the answer to both questions is "yes." In a survey by the Kaiser Family Foundation, two-thirds of American men said they would be willing to try the new pill. And in an international study of 4,000 men and women, more than two-thirds of the men said they would use a birth-control pill if it were available, and 75 percent of the women said they would trust their partner to handle the birth control [ref].

Just as the female birth-control pill had wide-ranging implications, the male pill could change the way men engage in sexual relationships. Health experts fear that the use of the pill among men who are not in monogamous relationships could reduce condom use and increase the spread of sexually-transmitted diseases.

But men probably won't have to worry about any of this for a few more years. Of all the male birth-control methods being investigated, the hormonal method is closest to reality, say researchers, and that's still a ways off. They estimate that a testosterone/progestogen birth-control drug should be available to men in about five years, but it will most likely come in the form of an injection or implant, rather than a pill. As for a male contraceptive drug in pill form, the future is more uncertain.

For more information on the future of birth control and related topics, check out the links on the next page.

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