Male contraceptive options in the pipeline
For years, the much talked-about male contraceptive pill has remained tantalizingly out of reach. What if the first contraceptive method to reach the commercial market relied on a nonhormonal approach instead?
Two such methods of male contraception are in clinical trials: RISUG (Reversible Inhibition of Sperm Under Guidance) and the Intra Vas Device (IVD). Both result in long-term infertility and have the potential advantage of being reversible.1
The Food and Drug Administration (FDA) has given the green light for a 90-man study of the IVD, now under development by Shepherd Medical Co. in Minneapolis. The feasibility study, which will be conducted in Seattle and St. Paul, MN, will examine the effectiveness of the IVD at blocking sperm, therefore causing reproductive sterilization, reports Janelle Antil, company clinical affairs manager. The National Institutes of Health in 2005 awarded Shepherd Medical Co. a $1.4 million grant to conduct human clinical trials on the device.
The IVD method relies on soft, hollow silicone plugs that are implanted in each vas deferens. Research in primates reported azoospermia in monkeys by the second to fourth ejaculation, with normal sperm counts returned by the second to fourth ejaculation following device removal.2 A small trial of the method in 30 men resulted in complete blockage or immotile sperm in 27 of the 30 men, with the remaining three men exhibiting very low motile sperm counts.3
Insertion is a simple procedure that requires only a few minutes to place each IVD, says Antil. 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.4
RISUG trial under way
The RISUG method relies on the injection of a polymer gel, composed of powdered styrene maleic anhydride combined with dimethyl sulfoxide, into the vas deferens. The gel coats the inside walls of the vas deferens and kills sperm. If restoration of fertility is desired, the polymer is flushed out of the vas with an injection of dimethyl sulfoxide.
In a Phase II clinical trial in 12 men, azoospermia was found as early as five days after injection; a subsequent trial reported comparable rates.5,6 Results from Phase I and Phase II clinical trials suggest that RISUG may be safe and effective as a contraceptive.5,7
Researchers in India are resuming trials of RISUG, following a four-year delay while initial concerns about side effects and insufficiency of genotoxicity data were addressed, states Elaine Lissner, director of the San Francisco-based Male Contraception Information Project (MCIP), a nonprofit organization designed to raise public awareness of pertinent research on the subject.
In 2002, when enrollment in the Indian study was halted, more than 140 men were using RISUG, states Lissner. Researchers subsequently conducted additional genotoxicity studies in India and the United States, and expert panels concluded that the major side effect — several weeks of nonpainful scrotal swelling in about one-third of the subjects — was not enough to stop the study.8
The developers of RISUG are arranging a collaboration with U.S. researchers, says Lissner. To gain FDA approval, American researchers would have to begin with animal tests, with testing in men several years away, she observes.
Many men and women in surveys, focus groups, and interviews say they want to share the responsibility for contraception.1 Those looking at RISUG in the United States should not be discouraged, says Lissner. "We already know that RISUG works, which is half the battle in drug development," she states. Men in studies in India have been using it for more than a decade, she says. "Now we just have to finish our homework."
- Upadhyay UD. New contraceptive choices. Population Reports. Series M, No. 19. Baltimore: Johns Hopkins Bloomberg School of Public Health, The INFO Project; April 2005.
- Zaneveld LJ, Burns JW, Beyler S, et al. Development of a potentially reversible vas deferens occlusion device and evaluation in primates. Fertil Steril 1988; 49:527-533.
- Zaneveld LJ, De Castro MP, Faria G, et al. "The soft hollow plug ("SHUG"): A potentially reversible vas deferens blocking device." In: Griffin PD, Rajalakshmi M, eds. Male Contraception: Present and Future. New Delhi: New Age International; 1998, p. 402.
- Burton J, Sievert C, Socha J, et al. Development and evaluation of the Intra Vas Device (IVD) — Poster. Paper presented at The Future of Male Contraception conference Seattle; September 2004.
- Guha SK, Singh G, Ansari S, et al. Phase II clinical trial of a vas deferens injectable contraceptive for the male. Contraception 1997; 56:245-250.
- Guha SK, Singh G, Srivastava A, et al. Two-year clinical efficacy trial with dose variations of a vas deferens injectable contraceptive for the male. Contraception 1998; 58:165-174.
- Guha SK, Singh G, Anand S, et al. Phase I clinical trial of an injectable contraceptive for the male. Contraception 1993; 48:367-375.
- Male Contraception Information Project. New male contraceptive clears hurdle. Press release. March 30, 2006.
- For more information on Shepherd Medical Co., send e-mail to IVDinfo@ShepherdMedical.com.
- The Male Contraception Information Project (MCIP) is a nonprofit organization with focus in three areas: raising public awareness of promising nonhormonal male contraceptives, advocating increased and expedited government research, and serving as a media resource for the subject. It works in conjunction with the Male Contraceptive Coalition, whose objectives are to speed the development of new male contraceptives through increased legislative and institutional support, raise funds for applied male contraception research and development, and provide public education on the research community's work. For more information on MCIP, visit its web site, www.NewMaleContraception.org. For more information on the coalition, visit its web site, www.malecontraceptives.org.