Progress reported on male contraceptives

While women have several options when it comes to birth control, men are limited to condoms and vasectomies. Researchers around the globe are focusing efforts to expand those choices, including hormonal injections, gels, and implants.

More than 100 investigators took part recently in the second "Future of Male Contraception" conference. The conference was sponsored by the National Institute of Child Health and Human Development (NICHD), CONRAD, the World Health Organization, and the University of Washington.

Since the last conference, there is a resurgence of energy emanating from the new male contraceptive research centers funded by the NICHD, says Elaine Lissner, director of the Male Contraception Information Project. Such funding from government and nonprofit sectors is imperative to male contraceptive research, because pharmaceutical companies have earmarked little funding for such investigation, she says. "I wouldn't so much say that the field has grown in the past three years; rather, I would say it has been rejuvenated, at a time when science research is being cut left and right, and the foundation has been laid for continued progress in the coming years," says Lissner.

Investigators are looking at several options when it comes to male contraception. Some of the avenues now under research include:

The Intra Vas Device (IVD), a vasectomy alternative under development by Shepherd Medical Company in Minneapolis. The IVD method relies on soft, hollow silicone plugs that are implanted in each vas deferens. Each plug is anchored to the vas wall with a tiny suture. The device can be inserted by any no-scalpel vasectomy provider and does not require extensive additional training. Preliminary results from a recent study show that after six months, 92% of the study participants had no sperm or almost no sperm.1 The next step will be to find funding for long-term studies of effectiveness and fertility return.

BMS189453, a retinoic acid receptor antagonist. Columbia University scientists are looking at an investigative drug that had been abandoned in previous research due to its interference with vitamin A receptors in the testes. Initial tests in mice by the Columbia research team indicate the drug works with no other health effects.2 Toxicology data in rats and rabbits, which were performed at much higher doses during the drug's initial development, indicate there should be no adverse side effects in humans. Further research will need to be performed to prove this line of inquiry, say the Columbia researchers.

Testosterone gel and depot medroxyprogesterone acetate (DMPA). Researchers from the University of Washington are examining a hormone regimen based on two products already available on the market: testosterone gel, marketed for men with low testosterone, plus DMPA, a contraceptive injection used in women. To perform the study, men received a DMPA injection once every three months and applied the testosterone gel on a daily basis. While the therapy achieved successful suppression of spermatogenesis, participants in the study had varied responses to the treatment. Six of 44 men dropped out of the study; the remaining were divided in opinion. Half said they were satisfied or very satisfied, one-third were dissatisfied or very dissatisfied, and the rest were undecided or had mixed feelings.3

What is the next step in research? The researchers are proposing an all-gel approach by using a testosterone gel along with a nestorone gel, reports John Amory, MD, MPH, associate professor of medicine in the Division of General Internal Medicine at the University of Washington.

Oral administration of testosterone enanthate (TE). University of Washington researchers are looking at coadministration with dutasteride to increase the efficacy of oral TE. Results of one study indicate a significant suppression of follicle stimulating hormone (FSH), but poor luteinizing hormone (LH) suppression.4 Researchers are considering nano-milled oral testosterone preparations for a male hormonal contraceptive.

Will men use it?

Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, is not overly excited about the news in the area of male contraception. His opinion? The two best — or close to best — contraceptives ever developed have been available since 1900: vasectomy and condoms. Vasectomy, after several negative semen analyses, approaches 100% effectiveness, but in only four nations in the world (New Zealand, the United Kingdom, the Netherlands, and Bhutan) do more men have vasectomies than there are women who obtain tubal sterilizations, says Hatcher.

"Condoms, a method that is 90% effective against HIV transmission, are used by well under 20% of couples at risk for transmitting HIV," Hatcher points out. "We've had excellent methods of birth control for men, and men simply do not step up to the plate and use them."

Results from an online survey of 1,930 men and women show that some men may be ready to change their ways if a new method is presented.4 The survey included responses gathered September 2006 to September 2007 during visits to the web site www.MaleContraceptives.org. Three-quarters of the respondents identified themselves as male, with 25% as female. Most respondents were of reproductive age (97%) and lived in the United States, Canada, or the United Kingdom.

Most male respondents said they would use a new male contraceptive. Two-thirds of men indicated enthusiasm about using any new male contraceptive, while one-third were interested in a particular contraceptive. More than half (61%) of the men said they would like to see a systemic nonhormonal drug as their first or second choice of mechanism.

Current contraceptive options are not appealing to many of the men: 43% of male respondents reported they would not be willing to have a vasectomy even if they did not want children. One-third of the men said their motivation for wanting new contraceptive options comes from a desire to share the burden of family planning with their partner.4

"We've seen today that the pipeline is full — everything from new targets to actual human trials," says Kirsten Thompson, director of the International Male Contraception Coalition. The demand is there, she maintains. "Hundreds of men have voiced their opinion on our web site and in surveys, so it's just a question of whether policy-makers act on that demand," Thompson says.

References

  1. Boelter C, Cline K, Stein DG, et al. Preliminary results of a clinical evaluation of the Intra Vas Device. Presented at the Future of Male Contraception conference. Seattle; September 2007.
  2. Chung SSW, Reczek PR, Wolgemuth DJ. Retinoic receptor alpha inhibitor as a contraceptive: RAR antagonists testicular toxins or new and novel male contraceptives? Presented at the Future of Male Contraception conference. Seattle; September 2007.
  3. Page ST, Amory JK, Kalhorn TF, et al. Testosterone gel plus depot medroxyprogesterone acetate is effective for male contraception but residual intratesticular androgens do not explain treatment failure. Presented at the Future of Male Contraception conference. Seattle; September 2007.
  4. Amory JK, Kalhorn TF, Page ST. Pharmacokinetics and pharmacodynamics of oral testosterone enanthate in oil plus dutasteride for four weeks in normal men: Implications for male hormonal contraception. Presented at the Future of Male Contraception conference. Seattle; September 2007.