Too much to swallow?

We've never had a male equivalent of the pill, but there are more prospects on the horizon than you might think

by Audrey Schulman

"Men don't like their private parts messed with."

This is how Elaine Lissner responds when I ask her a question I'd been wondering about for some time: why aren't there more contraceptives available for men?

"Also," she continues, "no contraceptive method is perfect at first. Without a lot of research money put into it, there's no way of creating a better method."

Lissner should know. Years ago, she was so interested in the question that she started the Male Contraception Information Project (MCIP). From 1991 to 1994, under the auspices of the Boston Women's Health Collective (the Somerville-based nonprofit that publishes Our Bodies, Ourselves), Lissner worked to publicize male contraceptives beyond the condom, and to change a very basic American assumption: that contraception is the responsibility of women.

Lissner combed through medical libraries, meticulously cross-referenced research articles, and amassed thousands of pages of information that even Planned Parenthood hadn't heard of. She was interviewed on National Public Radio and published an article in Ms. magazine that received an almost record response from readers wanting to know more. Meanwhile, for four straight years, Lissner and a grantwriter applied for grants to help support her unpaid work in the field.

"I applied for seven grants," she says, "and got none of them. Discouraged, I applied for one last $20,000 grant. Got $345." Shortly after this, she quit the field. When I found her, Lissner -- one of the country's experts on male contraception -- was an ESL teacher in San Francisco.

Lissner's fight was difficult for three reasons. First, there's the cultural assumption that contraception is primarily women's work. Second, in the age of AIDS, condoms have become so crucial that both genders have fixated on them as men's contraceptive contribution to the act of sex.

And third, as Lissner says, there's a huge amount of money at stake. Bringing a contraceptive to market, past the stringent guidelines of the FDA, costs an average of $70 million and can take up to 10 years. To risk that much, a pharmaceutical company has to believe firmly in the profit potential of the product. Until recently, companies believed that men had no interest in buying any contraceptive other than condoms.

What Lissner didn't know when she quit MCIP in 1994 was that the situation had already started to change. It started with worldwide polls showing that men increasingly want more, and better, contraceptives. For instance, one survey conducted in Germany showed that in the past 20 years, the percentage of men who want access to new male contraceptives has soared from 14 percent to 56 percent. And in the US, according to a national survey by the Kaiser Family Foundation, two-thirds of men now say they'd be willing to take a male version of the pill. (Strangely, fewer than half of all American women believe men would take the pill.)

Meanwhile, for the past 30 years, the World Health Organization (WHO), the Population Council, and the governments of such desperately overpopulated countries as China and India have been quietly working on their own male-contraceptive techniques.

And in the past two or three years, the pharmaceutical companies themselves have finally begun to fund male-contraceptive research. Perhaps the companies' interest is motivated by the massive success of Viagra -- a drug that men take specifically to mess with their private parts -- as well as by the consistent 20 percent annual sales increases of other reproductive-health drugs.

So now, finally, male contraceptives are in the US news. Four major drug companies are looking into male contraceptives; six articles on the subject have run in national magazines in the past month. Scientists at UCLA, Johns Hopkins, and the University of Washington are all working on the problem.

No one knows yet what the first new male contraceptive will be, but here are some of the most promising possibilities.

Nifedipine

In 1993, Susan Benoff, a leading researcher on male infertility in New York State, became interested in the case of a couple's unexplained infertility.

"Using fertility drugs, the woman produced 15 beautiful eggs, but none fertilized," Benoff says. The man's sperm acted normally in every way, but it couldn't impregnate the woman's eggs. "I took a careful medical history of the man," Benoff says, "and found he was on Nifedipine for his hypertension."

Nifedipine works by slowing the movement of calcium through cell membranes; Benoff knew calcium helps sperm to function. "My first question," she says, "was if I could discover past infertility cases where problems with Nifedipine were demonstrated. And the answer was yes. The next question was, Is Nifedipine's contraceptive effect reversible? The answer was yes."

Benoff had the man put on a different hypertension drug, and the couple got pregnant. To Benoff, the potential of Nifedipine as a male contraceptive was clear. The drug was safe, having been used for years on millions of men. She published her results, and her phone began to ring off the hook with men wanting to use Nifedipine as a contraceptive.

"From the way my phone rings," Benoff says, "there are a lot of men interested in more options."

Benoff was also approached by drug companies, but not with offers to fund her research. The manufacturers of Nifedipine wanted her work to stop: they were worried about lawsuits by men who had unknowingly been made infertile for years. "Perhaps between nine percent and 15 percent of all infertility cases are caused by Nifedipine," Benoff says.

Benoff hasn't stopped, but she's encountered a new research problem: Nifedipine's patent has expired. Without the promise of a proprietary drug at the end of the expensive research cycle, she says, "you can't get companies interested."

"Otherwise there's nothing to stop another company from packaging the drug with the same dosage. No money to be made," she says, and pauses. "The almighty dollar is what's driving this."

To get a new exclusive patent, Benoff and her lab have to create a drug very similar to Nifedipine. She thinks developing a safe and fully tested drug will take at least 10 years, although the research would go much quicker if she were ever to get major funding. "At least enough," she says, "to afford a second lab technician."

The male pill

The female pill uses hormones to trick the body into not ovulating. A male version would do something similar: use synthetic hormones to trick the body into not creating sperm.

It could be an extraordinarily successful drug. More than 100 million women worldwide now take some type of oral contraceptive daily; if you estimate the average annual expense per woman at $200, you can see that even a fraction of that number of men would represent a vast market.

In researching male contraceptives, I found five articles on the "male pill" for every article I found on any other contraceptive method. The Italians are working on it, as well as the Australians, the Brits, the WHO, and researchers at UCLA.

So far, most of the experiments have involved not a pill at all, but weekly injections. Even considering the pain of the injection and the hassle of getting to the doctor's office every week, men have apparently been lining up for drug trials. Fred Wu, a researcher at the University of Manchester in England, told the South China Morning Post, "When we made a request for volunteers, the switchboard was jammed for several days."

Right now, the closest thing to a usable product is being developed in Australia, by David Handelsman at the University of Sydney. His method is similar to the mechanism of the female pill: he uses the hormone progestin to suppress the hormone gonadotrophin (GnRH). Without GnRH, new sperm isn't produced. After three months on progestin, in a majority of men tested, no active sperm remain. As soon as the progestin is removed, GnRH kicks back in, starting the three-month-long cycle of restocking the sperm.

Tinkering with hormones, of course, is a dangerous game. It's one of the reasons a lot of women don't like taking the pill -- hormones affect every part of your body, from your brain to your digestive system. And there are side effects. So far, according to Handelsman's reports as well as others, these have included sleep disturbances, behavior changes, breast growth, acne, changes in cholesterol levels, and weight gain. And some men, for an unknown reason, just keep producing sperm.

Still, there's billions of dollars in it for whoever gets there first. Handelsman says the male pill might be available within five years.

For her part, Elaine Lissner says advocates of the male pill have been saying much the same thing for the past two decades.

Immunocontraceptives

The idea behind an immunocontraceptive is simple: use the body's immune system to attack a part of the sperm-production process.

There are a variety of ways this could work. Bill Stimson of Strathclyde University in England is working on a once-a-year vaccine that would provoke an immune response to follicle-stimulating hormone (FSH). The antibodies created gobble up all of the naturally occurring hormone. Without FSH, sperm are unable to mature. After the vaccine wears off, fertility gradually returns.

Conveniently enough, the FSH immunocontraceptive could be injected in the medium of a tetanus shot, so you'd be immunized against tetanus at the same time. So far it has been found to be nontoxic and reversible, but effective on only about two-thirds of all men tested.

Alternatively, scientists in Kenya and Argentina, and at two US universities, are experimenting with an immunocontraceptive that would create an immune response to the proteins that help sperm mature. Their research has gotten only to the point of being tested on rats and monkeys.

Prescription for change If the idea of a male contraceptive seems like a good one to you, there are a few things you can do. First, educate yourself about the possible options. Second, e-mail or call a medical-research company to let them know there are consumers eager for male contraceptives. Third, contact WHO, CONRAD, and the Population Council and lobby them to do more of the great work they've already done. In the words of Elaine Lissner, "Change takes people talking and organizing. Be persistent." Here are some useful contacts: AVSC. Informative international organization focusing on the social aspects of male contraception. E-mail: info@avsc.org. Contraceptive Research and Development Program (CONRAD). Based in Virginia, USAID's CONRAD does excellent research work. Phone: (703) 524-4744. E-mail: info@conrad.org. Family Health International. Articles and charts on contraceptives. Male Contraception Information Project. Run by the people in Somerville who brought us Our Bodies, Ourselves. This is the best site on the Internet for information about more-alternative contraceptive options. malecontraceptives.org. A brand-new site, started last month. They promise more information soon. E-mail: info@malecontraceptives.org. Population Council. This reproductive-health research organization has done much of the research into the male pill. E-mail: PubMed. If you want to do some nitty-gritty research, look up actual medical articles about male contraception here. ReproLine. Affiliated with Johns Hopkins University, this site offers good articles from a variety of sources. World Health Organization. WHO has pioneered much of the research on male contraception, keeping at it long after others have gotten discouraged. Drug companies that are researching male contraceptives: Glaxo Wellcome. Phone: (888) TALK2GW. Pfizer. Phone: (650) 624-9941. R.W. Johnson Pharmaceutical Research. Phone: (858) 450-2000. Schering-Plough. Phone: (201) 822-7000. Wyeth-Ayerst. Phone: (610) 902-1200. -- AS

SMA

Elaine Lissner calls this her favorite technique, one of the most promising but also one of the least researched. The polymer SMA (styrene maleic anhydride) can be injected with a small needle into the vas deferens, the tube that carries sperm from the testes to the exit. The procedure is minor; there's no need for even a local anesthetic.

Once inside, SMA partially blocks the vas and lowers the pH of the tube so much that the few sperm that get through die in the process. The SMA lasts for three months to five years, depending on how much is injected; fertility can also be restored by flushing out the polymer with another injection. In 1993, after 20 years of rat and monkey trials, 38 men tried SMA and found it to be safe, reversible, and effective.

In terms of marketing, though, SMA has two big disadvantages. One is that it could be administered as infrequently as once every five years. This dramatically cuts down on the potential profit to the company marketing it. The second disadvantage is that the process would be difficult to patent. (In medicine, a method cannot be patented; only devices such as forceps, or newly created drugs such as Viagra, can be.) Without the right to own the method exclusively, no company will take SMA through the excruciatingly expensive FDA approval process. Year after year, SMA continues to be clinically tested on animals, but it seems the only way this method will get to market is if a large nonprofit or government agency takes up the cause.

The Shug

The "Shug" is a silicone double plug with nylon tails that blocks off the vas. The double design ensures that no sperm can get out to create a pregnancy. (Think of it as a tiny condom located on the inside.) In a seven-month experiment, the University of Illinois found the Shug completely effective in creating reversible sterility in monkeys. It's implanted with two small puncture holes in the vas; the procedure takes only a few minutes and is accomplished with a local anesthetic. The Shug can be removed without a scalpel.

A variant of this idea is the "silicone injectable plug" -- a shot of liquid silicone injected into the vas. It dries in place and blocks the vas off. Unlike the Shug, the method can be reversed only once. In China, more than half a million men have received either Shugs or injectable plugs; all the men who had their plugs removed fathered children within four years, and most within the year. Injectable plugs are between 96 percent and 100 percent effective.

There are no known side effects aside from the possibility of permanent sterility caused by an immune reaction to the blocked-up sperm. It is not yet known how common this reaction might be.

The WHO recently tested silicone injectable plugs in the Netherlands and in Indonesia. Indonesia's test achieved results of 98 percent effectiveness, but the Netherlands' got only seven percent. The WHO is examining what went wrong -- there's some possibility that the European team injected too little silicone at too low a pressure.

If the WHO could get consistently positive results, it might start a program to bring the injectable plugs to different parts of the world, as it has with other contraceptive techniques. If such a program followed the WHO's general pattern, it would be offered first in countries that have intensive population pressures and less overwhelming safety-testing requirements. The US, in that case, would get plugs well after the rest of the world.

Ultrasound

Not every method of male contraception involves a pill or a plug. Some are as simple as a hot bath. Mostafa Fahim, a reproductive scientist at the University of Missouri, patented a method for inducing infertility using ultrasound, the same kind of technology used routinely on sports injuries and to view fetuses in the womb. The man's testes are cupped in a small basin of water, and the basin is gently heated for 10 minutes by an ultrasound element. Six months of sterility result.

It is thought that the ultrasound changes the levels of potassium and sodium in the testes, making the environment inhospitable to sperm. So far, no negative side effects have been discovered. The ultrasound itself is reported to be mildly pleasurable.

But there's a hitch. "After Fahim published his positive results," says Elaine Lissner, "a more well-known researcher published a paper contradicting him." This shut down interest in ultrasound in the US -- even though, according to Lissner, the dissenting researcher had done his work 15 years earlier using less advanced techniques.

Currently only the Chinese are using Fahim's method -- but in much longer applications designed to create permanent sterility. In spite of its promise, no work has been done on the temporary ultrasound technique since 1980.

Wet heat

Sperm is very sensitive to heat; that's why the testicles descend at adolescence -- to be outside of the hot body cavity. In 1946, Martha Voegeli discovered a very simple contraceptive method in India: a man can achieve six months of sterility simply by subjecting his testicles to a 45-minute-long hot bath -- at least 116 degrees Fahrenheit -- every day for three weeks. Strangely enough, the testes seem to be able to stand this heat much better than other parts of the body.

After 20 years of research, Voegeli found this method easily reversible, safe, and not linked to any later birth defects. She even found that treatment at a lower temperature but with more-frequent repetition can work.

In the US, more than 50 years after Voegeli's discovery, her positive results have started to be duplicated in studies on rats. Still, hot baths are not the sort of thing you can market easily, and so far, no company is putting research money into this method.

There are no official statistics yet on the overall reliability of wet heat. No matter how reliable it could turn out to be, the method would have to be monitored with regular sperm counts to make sure the procedure was effective in each individual case. If the water is even a degree or two cooler than recommended, the effect is markedly decreased.

Polyester suspensories
(tight underwear)

You can also cook sperm by wearing the right underwear. In 1992, Ahmed Shafik of Egypt proved that temporary sterility can be induced with specially designed polyester underwear that pushes the testes almost back up into the body. This elevates the sperm temperature at least two degrees Fahrenheit and as much as three and a half degrees; after four months of wearing the underwear during waking hours, there's no live sperm left. (The underwear has to be made of polyester to maximize the heat effect.)

Fifty percent of men in experiments conducted in France didn't mind the feel of the underwear at all. Five months after the men switched back to normal underwear, fertility returned. In 702 months of using the special underwear, there were no pregnancies.

However, according to Christina Wang of UCLA, if the testes are heated by less than two degrees, fertility still chugs along well enough to create pregnancies. So again, regular sperm checks would probably be a good idea.

No manufacturer has yet tried to bring the underwear to market. Selling underwear is not the way to riches, especially when the potential liability to the manufacturer would be in the millions of dollars.

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At the moment, the US is lagging behind the rest of the world in the development of male contraceptives. This lag is caused by tight FDA requirements, as well as by the wildly litigious nature of this country. When Norplant came out, the inventor, American Home Products, was hit with 50,000 lawsuits. The risk of this sort of legal tornado has scared off many US manufacturers.

The American tendency to sue is even making it difficult for the rest of the world to develop new contraceptives, because one of the main aims of a company in any part of the world would be to market the contraceptive to the huge and wealthy United States. We Americans, in other words, are holding everyone else back.

Still, there are positive signs on the horizon. American Home Products had only two scientists researching new contraceptive devices six years ago. Now it has 120 looking into both male and female contraceptives. At least three other major companies in the US are following suit, specifically in the field of male contraceptives.

Unless these companies succeed in their research, though, it is likely that the US -- a world leader in technology and medical research -- will, ironically, be one of the last nations to gain access to male contraceptives.

Audrey Schulman is a novelist living in Cambridge. Her last article for the Phoenix was "The Bare Witch Project."