Gene Tweaks and the Male Pill: Contraception of the Future?

Oct. 19, 2007— -- The Pill. Condoms. Intrauterine devices.

They are staples of modern birth control. And while they represent some of the best options that men and women have at their disposal today to prevent pregnancy, each is decades old -- and comes part and parcel with a number of its own drawbacks.

"We want more choices," says Laura, a 37-year-old Florida woman who preferred that only her first name be used.

"Science has come a long way, but why are contraceptive options lagging behind?"

But researchers are exploring a host of new options for those who are tired of side effects from the pill and wary of the user dependability of condoms. Indeed, some are looking forward to a new wave of contraceptive strategies -- which could well represent the first long strides after the baby steps of progress since the sexual revolution.

Taking It to the Genes

One such option, which upon its unveiling garnered chatter in the U.K. press, has generated enthusiasm for the idea of genetic contraception. In fact, it could one day become the first of an "entirely new class of contraceptives," leading researcher Dr. Zev Williams hopes.

Williams, a clinical fellow in the department of obstetrics and gynecology and reproductive medicine at Brigham and Women's Hospital of Harvard Medical School in Boston, presented research at the annual meeting of the American Society for Reproductive Medicine in Washington Tuesday that he says, if successful, "will mark the first serious advance in contraception since the introduction of the birth control pill.

"For the last 60 years, women have had three choices: hormones, the IUD and barrier method -- the condom," Williams says. "The only advancement has been from a nonchewable to a chewable form of the pill, and yet these three options are still all there is.

"We simply don't have a contraceptive drug that is nonhormonal and reversible."

The genetic contraceptive that Williams is developing is based on a concept known as RNA interference (RNAi) -- a process that switches off key genes in a woman's body that play a crucial role in the fertilization of the egg after sex. When these genes are switched off, her partner's sperm cannot enter the egg to fertilize it.

Zev believes that this method will avoid many of the side effects of traditional birth control pills, because it will not flood the body with sex hormones.

"For women who use the pill just as a contraceptive, a nonhormonal approach would be wonderful, says Zev. "You could get all the benefits without the nausea, the headaches, the mood alterations and the raised risk of thrombosis, strokes and heart attacks."

The theory behind genetic contraception builds on similar research among two American scientists, Craig Mello and Andrew Fire -- research that won them the Nobel Prize last year for their work.

If the method works safely in animals, a product could be available within 10 years. While the mode of delivery is yet to be determined, Williams says, it "may be in a vaginal suppository or transdermal form.

"A pill form would be less likely due to acidity in the stomach, which may interfere with the RNAi, but a coated pill may be a possibility," he adds.

However, outside experts say there is much left to be done in terms of research before such a genetic option can become reality.

"This may translate into a useful alternative for women, but there's a long way to go," says William Ledger, professor of obstetrics and gynecology at the University of Sheffield in the the United Kingdom.

"This research will obviously take time and serious money to carry out," he says, adding that he remains concerned as to whether or not the method is reversible. "Young women want a safe and effective contraceptive that is rapidly reversible when they decide to have a child."

Williams says that experiments are ultimately needed to determine the reversibility of this option. But he notes that despite the preliminary state of the research, some biotech firms are already onboard.

Male Contraception: Not So Close

While many men may also be eagerly anticipating a male form of the birth control pill, contraceptive injections or the patch in the near future, their wait may be a bit longer.

"Marketing studies showed that at least half of men were interested in the male method of contraception," says Dr. Christina Wang, professor of medicine at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

Despite men's apparent willingness to try a new way not to get their partners pregnant, speculation among two key NIH research groups (one of which is headed by Wang) reveals that these alternative forms of male contraception may not be available in the near future after all.

"Pharmaceutical companies have not had as much interest in male contraception as fields such as oncology and cardiology," says Wang. "Because of mergers and low profitability, pharmaceutical companies have decided rather to focus on female health.

"It all comes back to the pharmaceutical industry; it all depends on the funding."

Dr. John Armory, who heads the other NIH research group at the center for research and reproduction and contraception at the University of Washington School of Medicine in Seattle agrees, adding that paltry returns on investment often encourage pharmaceuticals to focus on other pursuits.

Wang, however, remains optimistic, citing a recently completed Chinese clinical trial that tested the effects of male chemical contraceptives in 1,000 men over two years, as well as a similar trial in Europe that included 350 men over an entire year.

The verdict? Wang says the drawbacks, at least for the time being, appear mild -- acne, oily skin and weight gain.

However, she says, long-term drawbacks are not yet known. And Armory adds another notable side effect -- "a reduction in testicular volume."

He is quick to add, however, that testicular volume reduction does not mean a reduction in penile size.

"Men haven't complained because reduction in testicular size is reversible," he adds.

Wang says that if (and it's a big "if") industry funding appears, she believes that male contraception will start with an injectable form, then an implant and then a pill -- possibly within the next five years.

Meanwhile, while waiting for funding to support the male contraceptive market and watching the development of genetic contraception, what are we to do?

Eli Coleman, professor and director of the chair in sexual health at the University of Minnesota Medical School in Minneapolis, believes that nonhormonal methods for women would be very welcome.

"Side effects from hormonal methods -- including lowered libido -- are often troubling to many women and couples," she says, adding that she currently favors improved condoms, spermicides and microbicides.

But Coleman cautions against contraceptives that do not offer protection beyond pregnancy, such as against HIV.

"Let us not forget that condoms offer the best protection against pregnancy and sexually transmitted diseases," she says.