My teenage nephew came to visit last summer, and I asked him if there was anything he needed from the drug store. “Uh, condoms?” he said. It was easier to ask liberal Aunt Val than Grandma, who is raising him. We hopped in the car. At the local Walgreens, we found the display and we lingered, picking packages up and putting them back. “Wow, there’s a lot of choices,” he enthused, exchanging a rainbow of colors for a fruit-flavored variety pack. I bit my tongue to keep from pointing out that we were seeing a lot of packaging but only a single type of latex device, vulnerable to misuse and rupture. I was determined to focus on the positive, making our shopping excursion as normal and playful as possible—to make condom buying (and wearing) an absolutely ordinary thing to do. For 20 years, ever since the HIV epidemic swelled to global proportions, aunts, parents, schools, public health agencies, and governments around the planet have been trying to do the same thing: indelibly pair condoms and sex. Condoms are the best thing we have going for prevention of sexually transmitted diseases.

Unfortunately, all the focus on HIV and condoms has drawn attention away from another reality: from a contraceptive standpoint condoms are mediocre at best. While the top tier of female birth control methods (IUDs and implants) have an annual pregnancy risk as low as 1 in 1,000, the annual risk for a couple using condoms is closer to 1 in 5. Multiply that by almost 40 years of female fertility! Reliance on condoms is one of the reasons that 1 in 3 American women has had an abortion by the time she hits menopause.

As my nephew and I stood in line at the cash register, I thought about how proud I was that even with a challenging home situation and only a grandmother to guide him, he was taking responsibility for himself. Then I thought, “I wish he had better options—like something we could count on!” Thanks to some determined researchers and funders, my wish may come true in time to give my nephew real choices as he moves into adulthood. In contrast to the frustrating options at the pharmacy, an array of promising possibilities can be found in various stages of research around the globe. Here are some of the top contenders.

Clean Sheets Pill

(London, Oxford) Dr. Nnaemeka Amobi and his team are researching a hormone-free method that has been dubbed the “clean sheets pill” because it decreases or eliminates semen emission while leaving intact the sensation of ejaculation and the pleasure of male orgasm. The pill works by relaxing just the muscles in the vas deferens that normally propel sperm-containing semen forward and out. Without the forward propulsion, circular muscle contractions essentially close down the passage. Reducing or eliminating emission of semen not only prevents pregnancy, it also decreases the spread of semen-born diseases, including HIV. The hope is that this medication can be delivered via pills that men take before sex—much like Viagra.

RISUG

(Kharagpur) More than 250 men have undergone a procedure named RISUG, which stands for reversible inhibition of sperm under guidance, that researchers hope will provide a cheaper and more reversible alternative to vasectomy. A liquid polymer is injected into the vas deferens, where it provides contraception for up to ten years. In the duct, the positively charged polymer reportedly acts almost like a magnet, reacting with the negative electrical charge on the membranes of passing sperm and rendering them infertile. In research with rats and primates, fertility has been restored by a noninvasive procedure that removes the polymer. Human clinical trials of RISUG are moving forward slowly in India.

Vasalgel

(San Francisco) Inspired by RISUG, a similar polymer, dubbed Vasalgel, is under development in the United States, with rabbit research now underway to meet FDA standards and primate studies planned. Over 18,000 men and women have signed up to receive information about clinical trials, expected to begin in 2014.

Ultrasound

(Chapel Hill) Therapeutic ultrasound is a common sports medicine treatment for injured joints and muscles. A brief massage of the testes with the same instruments has been shown to reduce sperm count in both animals and humans. Doctors have long known that heating the testes even to body temperature reduces fertility, and we know that therapeutic ultrasound produces a deep warmth. But for reasons that are unclear, the contraceptive effect of ultrasound is ten times that of heat alone. Depending on the level of exposure, contraceptive duration ranges from six weeks to permanent. One major challenge at this point is to find a treatment regimen that is either reliably reversible or reliably permanent. Of the two, use as a nonsurgical vasectomy option is more likely.

Gamendazole

(Kansas City) Potential contraceptives are sometimes discovered as side effects of other medications, and gamendazole derives from a cancer treatment that by chance was noted to decrease male fertility. Research shows that the drug works by interrupting sperm maturation. Men taking gamendazole produce and release normal quantities of sperm, but the sperm are “nonfunctional.” In mating studies of rats, the drug achieved 100 percent infertility and was fully reversible. Research with monkeys looks promising.

Adjudin

(New York) Like gamendazole, adjudin is an analogue of a cancer drug, lonidamine. It works the same way, causing sperm to be released when they are immature. For lonidamine, the gap between a contraceptive dose and a toxic dose is small, making the drug too dangerous to give to healthy people. But researchers at the Population Council were able to create a related compound that is taken up only by the precise receptors in the testes where it is needed for contraception. This dramatically reduces the needed dose. Two remaining drawbacks to adjudin are that it can be administered only by injection, and its effect is short-lived. Researchers are working to devise a version that doesn’t require frequent injections.

JQ1

(Waco, Boston) JQ1 is related to some familiar drugs, Valium and Xanax, but it has a very different effect. Instead of bringing on sleep or reducing anxiety, it blocks production of a protein in the testes that is essential to sperm growth. In mice that are given JQ1, the number of sperm takes a nose dive, and those that are produced don’t swim very well, which makes the mice infertile. Sex drive remains unaltered, and after the drug is stopped, sperm production rapidly returns to normal.

Testosterone and Progestin

(Beijing, Los Angeles, Seattle) If injected or absorbed through the skin, testosterone alters hormonal messaging and reduces production of sperm. When combined with a progestogen and rubbed on in gel form, a daily application has effectively suppressed sperm concentration in almost 90 percent of men, with few side effects. Current research, which builds in part on work done at the University of Washington and UCLA, is exploring the best combination of testosterone and progestin, and how such a combination can be delivered to provide long-acting birth control.

With such a variety of options (and more) in the works, it seems like something new for men should be just around the corner. But much of the research is progressing at a snail’s pace due in part to regulatory barriers and lack of funding. Contraceptives get used by young healthy people, which means that the bar for safety and efficacy is much higher than for many other drugs. A cancer treatment might be welcomed if it has a 70 percent success rate and makes your hair fall out. Needless to say, either of these is a non-starter for a new contraceptive. The high bar (and the corresponding high risk of liability) makes drug companies and even philanthropists wary of investing in contraception—which has to be almost 100 percent effective and side effect free to be a success.

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Will any of these options make it to market in the next five years? That depends in part on whether drug companies, nonprofit research funders, and public health experts think we’re ready. Do men really want to take responsibility for contraception? Will women trust them to do so? Those questions are the focus of Part III in this series.

Thanks to S. Minden for her expert editing eye on this series.