Hormonal-based male contraceptive moves ahead

Clinical trials expected to start this year

Clinical trials for a male contraceptive that is a combination of progesterone and testosterone are expected to begin this year.

The study is being conducted by the Bethesda, MD-based National Institute of Child Health and Human Development of the National Institutes of Health, reports Diana Blithe, PhD, program director. The research will be conducted at two clinical sites: one headed by Christina Wang, MD, at Harbor-University of California, Los Angeles Medical Center in Torrance, and the other headed by William Bremner, MD, PhD, at the University of Washington in Seattle. The test product is a combination of two gels, testosterone gel and Nestorone gel, with the latter to be prepared and supplied by the New York City-based Population Council.

While surveys show men are very interested in having a male contraceptive and might prefer an oral contraceptive, the problem is that hormonal-based contraceptives can cause unpleasant side effects, experts say.1

Male contraceptive researchers note that the same side effects have posed problems for female contraceptives as well. Researcher Deborah O’Brien, PhD, associate professor at the University of North Carolina School of Medicine in Chapel Hill, says, "The concerns some of us have are the same as for hormonal contraceptives for women. They’re systemic and so are likely to have side effects elsewhere, and that’s true with any hormonal contraception."

For example, if a hormonal contraceptive shuts down on testosterone production, there likely will be feminization side effects, which are not very desirable and acceptable to men, says Michael Rosenberg, MD, MPH, clinical professor of obstetrics/gynecology and epidemiology at the University of North Carolina-Chapel Hill and president of Health Decisions in Chapel Hill..

"The real issue is the ability to do the testing on these contraceptives well enough and quickly enough to refine the products and take them through the testing stage pretty quickly," he says.

They will take a lot of refinement and require balancing, he notes. "Look at female contraceptives and how hormonal balance has been handled," Rosenberg notes.

The advantage to hormonal contraceptive approaches is that these types are the furthest along in the male contraceptive pipeline, says Blithe.

Hormonal contraceptives were the first to make it to clinical trials, including etonogestrel in implant form and testosterone undecanoate in injection form, which have had Phase II trials in Europe. And a Phase III trial of injectable testosterone undecanoate was conducted by the Geneva-based World Health Organization last year in China.

Most hormonal approaches impact testosterone production in the testes to reduce sperm production and then provide serum testosterone to prevent feminization, so other body functions will be normal, but the man will not produce sperm, Blithe says.

NIH conference featured latest research

The Future of Male Contraception conference, sponsored by NIH, and held Sept. 29-Oct. 2, 2004, featured a variety of lectures and poster abstracts about hormonal approaches. For example, one new study tested 22 healthy young men who received eight weeks of combined testosterone and levonorgestrel treatment to augment gonadotropin and intratesticular androgen withdrawal with the goal of providing greater spermatogenic suppression.2

The treatment significantly decreased intratesticular androgens from baseline.2

Other new research discovered that nonsteroidal selective androgen receptor modulators provide a potential alternative for testosterone replacement therapies, including hormonal male contraception.3

"There are very intriguing sets of research done so far," Rosenberg says. "The problem is being able to provide contraception without impairing other things that are important, like secondary sex characteristics and like passing the blood-testes barrier. You want a drug to act in the testes, but not anywhere else."

Since male contraceptives are so early in development, it’s difficult to say what ultimately will work best, but it appears that safety issues will be the biggest hurdles, Rosenberg says.

"The ability of a male contraceptive to increase a person’s desire and not diminish his performance and eliminate worry about pregnancy would be very desirable," he says. "There’s a real parallel with the development of female contraceptives. It’s been in refining the safety."

References

1. Weston GC, Schlipalius ML, Bhuinneain MN, et al. Will Australian men use male hormonal contraception? A survey of a postpartum population. Med J Aust 2002; 176:208-210.

2. Matthiesson KL, Stanton PG, Amory JK, et al. Effects of testosterone and levonorgestrel combined with a 5-alpha reductase inhibitor or long-acting GnRH-antagonist on serum and intratesticular reproductive hormone profiles. Presented at the Future of Male Contraception conference. Seattle; Sept. 29-Oct. 2, 2004.

3. Chen J, Hwang DJ, Miller DD, et al. An orally bioavailable selective androgen receptor modulator (SARM) for hormonal male contraception. Presented at the Future of Male Contraception conference. Seattle; Sept. 29-Oct. 2, 2004.