Personal Health

Birth Control for Men? 3 Promising Advances

The joke in the male contraceptive field goes that we've always been five years away from male contraception being available.

While women have had hormonal, reversible contraceptive since the 1960s, men simply don't have a form of birth control comparable to the pill. Too bad; studies conducted by the World Health Organization show that men from many countries around the world would gladly welcome such a development.

There are condoms, and vasectomies, but both methods have their downsides. Condoms can break. (And, honestly, who likes using them, anyway?) Vasectomies, while effective, are permanent. Also, although the pill for women has been deemed safe, there are still side effects and putting all the pressure on the female partner is hardly fair either. 

Why has it taken so long to develop these methods for men? The challenge is twofold. The first lies in differences in biology. During pregnancy, the hormone progesterone naturally halts ovulation. Men, however, never stop producing sperm. There are other obstacles, such as funding for further research and a lack of pharmaceutical companies taking an interest in the field. But, as scientists tell me, we could be only a few years away from temporary, reversible, male contraceptives.

Progestin

Dr. Diana Blithe, program director of the Contraceptive Development Research Centers Program funded by the National Institutes of Health, says the most effective known method is to administer some sort of progestin molecule, a synthetic hormone similar in function to progesterone which regulates pregnancy in women.

In men, however, the progestin suppresses the body's ability to make enough testosterone to support sperm production, so sperm count levels drop well below what's needed to fertilize an egg under normal circumstances.

But when administering progestin to men, it's necessary to administer back some androgen like testosterone. Without it, Blithe says, a man would begin to experience hot flashes and have trouble achieving an erection. Testosterone is currently commercially available as a transdermal gel, but development of an oral form remains a challenge.

There are several ways to administer the progestin: daily pills or gels, and long-lasting implants or injectables. Men could choose the method they prefer. Blithe thinks the long-lasting versions would make a better option; unlike pills, the injection or implant do not depend on remembering to take it.

"A lot of reasons why [birth control] fails in women is simply because they forget to take it," she says.

The testosterone replacement part, however, could be effective in daily dosage form. "If you don't take it, you start to feel the effects," explains Blithe. "That's self-motivating in that respect."

Blithe says two European pharmaceutical companies collaborated to conduct a large trial of male fertility while using an progestin implant and a testosterone shot, and the results were good. But the companies were taken over in mergers and people at the top decided to focus in areas that were more lucrative.

In order to get FDA approval for this method, a company would need to conduct a similar large-scale study in the U.S. showing the technique's effectiveness.

Gel

Dr. John Amory, an associate professor of medicine at the University of Washington, is currently in the middle of clinical trials testing a combination of progesterone and testosterone. The study is being conducted at the University of Washington and at UCLA.

How does this gel work?

First, a simple explanation of male fertility: To make sperm, the brain first tells the pituitary gland to secrete two hormones, LH and FSH. In men, those hormones affect the testes, signaling them to produce sperm and testosterone. The testosterone then gets into the bloodstream and goes back to the pituitary, which helps regulate its own production.

The gel approach would simply boost the amount of testosterone in the man's bloodstream.

"It's what we call a negative-feedback loop," explains Amory. "If you give somebody testosterone from the outside, in a dose slightly more than their body would make, it will suppress the production of LH and FSH in the pituitary. That deprives the testis of the signals that are required for spermatogenesis."

Amory's current study is looking into the effectiveness of a "gel-gel" approach -- using two gels to suppress sperm production. One gel contains progesterone, the other testosterone. Men apply the gels once a day.

"It's like putting on sunscreen," Amory says.

It should take about two to three months for the gel treatment to become effective. And, the good news is, it should be completely reversible. Men should begin producing sperm again about three to six months after they stop using the gels.

Retinoid

Dr. Debra Wolgemuth is a professor of genetics and development at Columbia University. For the past five years, she's researched new methods in male contraception; one of the most promising involves the use of inhibitors of retinoids, metabolites of vitamin A.

Her investigation into these retinoids inhibitors as a contraceptive began when she came across a paper showing that scientists at Bristol-Myers Squibb had synthesized compounds that proved toxic in the testes. A light bulb went on.

"One person's toxin can be another person's contraceptive," said Wolgemuth in a phone interview.

As you probably know, vitamin A is a compound found in foods like carrots, liver and broccoli, but it has to be converted into an active form before it can be used in biological processes. One of its active forms is retinoic acid, which affects processes such as gene expression.

In the testes, retinoic acid binds to proteins in the cell called retinoid acid receptors, which regulate the production of various proteins needed for sperm formation. Block those proteins, and sperm don't form correctly, making the male infertile.

In earlier studies, Wolgemuth found that male mice with a mutation at one of the retinoid acid receptors were sterile, while females with the same mutation were still fertile.

There's still a lot of work to do in understanding how retinoid inhibitors could be used for male contraception. Wolgemuth is trying to figure out at which point during the process of cell differentiation that sperm production is disrupted.

"It's a very complex process," she said. "It takes weeks to make a final, mature sperm."

Wolgemuth's latest scientific paper shows that using retinoid inhibitors to induce infertility is reversible, one of the key components to creating a marketable contraceptive.

"We're trying to ask questions like, how long can we keep the mice on the drug and still allow them to regain fertility when we stop? And we're also interested in how low a dose we can give," she said.

Diana Blithe says there are certainly plenty of people interested in male contraceptive options similar to those now available to women. That's especially true with couples where the woman can't take hormonal contraceptives for health reasons such as diabetes or obesity.

Ted Cox is a writer from Sacramento, Calif.
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