2015-02-17

Every couple of months, starting in 2008, clinicians injected dozens of men across eight countries with a serum containing the hormones progestin and testosterone. The men then had unprotected sex with their female partners, as part of a male-birth-control trial orchestrated by Conrad, a Virginia-based nonprofit devoted to reproductive-health research. Three years into the trial, things appeared to be going well: just four women had gotten pregnant.

There was one big catch, however. While Conrad had anticipated that the hormones might have a few minor side effects—weight gain and acne among them—some of the men developed more-severe reactions, including depression and ramped-up libido. This spooked the panels that were overseeing the experiments, and in April 2011, Conrad shut down the study.

Though they’re used by almost everyone, contraceptives seem to have advanced less in 50 years than cellphones have in five. The problems with the current birth-control arsenal are well known: The pill is the most common female contraceptive method in the United States, but nearly a third of American users are so dissatisfied that they abandon it within the first year. That’s because the pill, like all hormonal forms of birth control, can have a number of negative side effects, including nausea and mood changes. Intrauterine devices and implants are by far the most-effective forms of reversible birth control, but the only nonhormonal version on the U.S. market—the copper IUD—can cause severe cramping and heavy bleeding. Barrier methods, meanwhile, have high failure rates.

The obstacles to introducing new methods are enormous. Even if a research lab were to develop a promising product, that lab would need a pharmaceutical company to bring the drug to market—and the pharmaceutical industry’s support for new contraceptives has been tepid. Drug companies are wary of cannibalizing the existing oral-contraceptive market, and of being sued. Women routinely assume certain health risks from birth control, perhaps because the alternative (pregnancy) has its own hazards. Pharmaceutical companies seem less confident that men (who are in no danger of getting pregnant) will embrace a male contraceptive despite its side effects or hassle factor. In 2007, for example, Bayer shelved a male contraceptive that involved an annual implant and a quarterly injection, having concluded that men would consider the regimen—in the words of a spokesperson—“not as convenient as a woman taking a pill once a day.”

And yet, improved birth control could be life-changing. Currently about half of all pregnancies are unintended; lowering this rate would in turn reduce the number of children born into poverty, cut the abortion rate, and possibly trim health-care expenditures. Many researchers also believe that male birth control would advance gender equality by making contraception a shared responsibility (and, as in the case of the Conrad study subjects, a shared pain).

Here, drawn from interviews with researchers, are glimpses of a number of contraceptive technologies in various stages of development—none of which involves women taking a daily pill.

A reversible alternative to the vasectomy: Despite their 99 percent success rate, vasectomies remain fairly rare—only about 13 percent of married men of reproductive age report having had one. Their unpopularity is commonly blamed on their intimidating “snip snip” element and on the fact that they aren’t always reversible. The Parsemus Foundation, a nonprofit that supports medical research, is working on a reversible, snip-free alternative to the vasectomy. A doctor would puncture the scrotum and inject a polymer jelly called Vasalgel into each of the vasa deferentia, the tubes through which sperm travel. There, it would form a flexible, porous plug capable of filtering out sperm. To restore fertility, the vasa deferentia would be flushed with a solution that dissolves the gel. Researchers have tested the procedure on rabbits and baboons; human trials are planned for later this year. Parsemus’s approach to funding is novel, too: it’s collecting donations from people who have expressed enthusiasm about the product.

A better diaphragm: Conrad, together with the international nonprofit Path, recently created a new diaphragm called the Caya. Unlike older models, it’s “one size fits most,” the idea being that women should be able to buy a diaphragm off the shelf, without first undergoing a pelvic exam. The device also features a nylon spring and “grip dimples” to help with insertion. The Caya, which is already being sold in Europe, has been approved by the FDA and is expected to be available in the U.S. this year. If it takes off in rich nations, Path’s Jane Hutchings told me, the earnings will be used to subsidize distribution in the developing world.

A remote-controlled implant: A Massachusetts-based company named Microchips Biotech has created a postage-stamp-size implantable device that stores medication and dispenses precise doses at scheduled intervals. The device has already been tested with various (noncontraceptive) drugs, and this year, with Gates Foundation funding, the company will test its ability to release a slow trickle of levonorgestrel, the progestin hormone found in many birth-control pills, for up to 16 years after implantation. The drug would be hermetically sealed inside the device, along with an antenna and a battery; a woman could use a remote control to “pause” drug delivery when she wanted to conceive.

A testosterone gel: The National Institute of Child Health and Human Development is nearing a second round of clinical trials of a hormonal gel that men are directed to rub daily on their shoulders (a place that’s “not too hairy and not too sweaty,” the NICHD’s Diana Blithe told me). The gel contains Nestorone, a synthetic progestin that, by inhibiting testosterone production, stops the testicles from making sperm. The drug would also deliver testosterone to the blood, in an effort to prevent any change in libido, ejaculation, or muscle mass. Blithe says she hopes the gel will make for an appealing alternative to vasectomies and condoms.

Antibodies from plants: By inserting human genes into plants, scientists have been able to create disease-fighting proteins called “plantibodies,” which work just like the antibodies that the human immune system makes to ward off infections. Harvesting such proteins from plants—many plantibody researchers work with tobacco—is far cheaper than growing them in human cell cultures.(The world got a preview of plantibodies at work with ZMapp, the plantibody-based experimental drug that has been used to treat a handful of Ebola patients.)

Researchers headed up by a team at Boston University are working to create a combination of plantibodies that would combat sperm, herpes, and HIV. The plantibodies would trap sperm and germs in vaginal mucus, paralyzing them until they are cleared from the body. Only the herpes and HIV plantibodies have been tested so far, and only in animals; sperm plantibodies are at an earlier stage of development. But eventually, the researchers hope to load all three proteins into a vaginal ring that would provide monthlong protection.

Far-off methods: Other proposed contraceptive technologies are, you could say, still zygotes in the drug gestational cycle, thanks to a myriad of funding and scientific hurdles. For years now, the U.K.-based doctors Nnaemeka I. B. Amobi, Christopher Smith, and John Guillebaud have been at work on something they call the “clean-sheets pill,” which would allow men to have dry orgasms. (The zing of an orgasm can be experienced without semen emission, Amobi maintains.) The pill has already been tested in rams, but Amobi says they need a $400,000 grant to take their research further.

John Amory, a professor of medicine at the University of Washington, is attempting to develop a drug that would inhibit vitamin A from converting into retinoic acid in the testicles. This, in turn, would halt sperm production. It’s a risky path: a 1950s male pill that involved vitamin A was abandoned because it made men violently ill whenever they consumed alcohol. Amory says he’ll consider himself lucky if he has a viable drug within 10 years.

“Sometimes I think, Could I have chosen a more complicated research endeavor?,” Amory says. “It’s not nuclear fusion, but it’s pretty complicated.”

This is the second installment in the print and online series Shifts, about the elements of a changing world, from technology and business to politics and culture. For more information, visit theatlantic.com/shifts.

A Brief Chronicle of Contraception

1564: The first modern condom, a linen sheath tied with ribbon, is credited to Gabriello Fallopio (of the tubes).

1823: A British surgeon performs the first recorded vasectomy—on a dog.

1916: Margaret Sanger opens America’s first birth-control clinic, in New York City.

1960: G. D. Searle & Company markets Enovid as the first contraceptive pill.

1990: The FDA approves Norplant, the first contraceptive implant to be marketed in the U.S.

2022: A testosterone-based male-birth-control gel comes to market.

1876: Oscar Hertwig’s work with sea urchins proves that fertilization involves the fusion of sperm and egg nuclei.

This article was originally published at http://www.theatlantic.com/magazine/archive/2015/03/block-that-sperm/384971/



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