Male contraception: Search is on for options

When women enter your family planning clinic, you have a wide array of contraceptive options to offer them. But when men ask about prevention methods, you have three choices: hand them condoms, advise abstinence, or counsel on vasectomy.

While 2002 saw the introduction of the contraceptive patch and vaginal ring for women, no contraceptive method emerged on the commercial marketplace for men. However, researchers report that investigation of male methods is enjoying a resurgence in interest, as hormonal approaches may have acquired the critical mass needed to make the transition from academic research to pharmaceutical development.1

To expedite development of new approaches to regulating fertility, the Bethesda-based National Institutes of Health has awarded a five-year, $9.5 million grant to the Seattle-based University of Washington to establish an interdisciplinary Male Contraception Research Center. The center will be part of the Cooperative Contraceptive Research Centers Program, funded by the Contraception and Reproductive Health (CRH) Branch of the National Institute of Child Health and Human Development.

In addition, the CRH has issued a request for applications that are focused on novel approaches to male fertility regulation, and it has issued a request for proposal for clinical trial expertise in male contraception, says Diana Blithe, PhD, CRH scientific officer.

Defining the challenge

Why has it been so difficult to develop a viable male contraceptive? Consider the challenging physiological task of controlling the male reproductive system. While a woman produces one egg a month, a man produces hundreds of millions of sperm each day. Women are fertile only until menopause; men continue to produce sperm throughout their adult lives.2

Current research approaches in male contraception primarily are focusing on two mechanisms of action. One approach is aimed at suppressing the production of sperm, by hormonal or nonhormonal means, while the second avenue seeks to inhibit the fertilizing ability of sperm.2

Researchers have looked at administering doses of testosterone to achieve blood concentrations that are significantly higher than normal. This causes the male pituitary gland to slow the release of two hormones — follicle stimulating hormone (FSH) and luteinizing hormone (LH) — that produce the signals necessary for sperm development. FSH and LH act in a feedback loop to maintain normal concentrations of testosterone.3

Scientists also have looked at progestins to block testosterone production in the testes, which hinders sperm formation. Since this approach results in a drop in testosterone concentrations in the blood, researchers have administered low doses of testosterone in conjunction with the progestins.3

Results of two recent investigations indicate such approaches may be effective. One study, which looked at the use of testosterone decanoate injections and etonogestrel implants, suggests that spermatogenic suppression is achieved.4 In the other study, investigators compared levonorgestrel implants and testosterone transdermal patch to testosterone patch alone on the suppression of spermatogenesis.5 The scientists expanded their research to include use of a combination of oral levonorgestrel and testosterone patch, as well as use of levonorgestrel implants and testosterone enanthate injection. Results indicate that the implant/injection option was the most efficient in suppressing spermatogenesis to a level acceptable for contraceptive efficacy.5

New androgen eyed

The New York City-based Population Council is examining several research options in male contraception using its trademarked synthetic androgen, MENT (7 alpha-methyl-19-nortestosterone). While the synthetic steroid resembles testosterone, MENT does not enlarge the prostate, a drawback that occurs when testosterone is given exogenously. The Population Council is researching a MENT implant, transdermal gel, and patch formulation for contraception purposes.

Dose-ranging studies are under way in Germany, Chile, and the United States, using MENT alone and MENT associated with other agents to achieve a complete suppression of sperm production in male volunteers, states Regine Sitruk-Ware, MD, the council’s executive director of contraceptive development. When the appropriate dose is determined, researchers will begin a study with couples volunteering to test the method for contraception. This step will not be possible before scientists are certain of achieving 100% suppression of sperm production, she notes.

A large-scale contraceptive efficacy and safety study would not start before mid-2004; it would include 300 couples followed for one year, and it also would document recovery of fertility in a further year of follow-up, says Sitruk-Ware.

"If the results are successful, we would then have to document efficacy and safety in 1,200 couples followed over one year of therapy," she states. "Given these requirements, the method would be approved and available for general use most likely in year 2008 or 2009."

References

1. Anderson RA, Baird DT. Male contraception. Endocr Rev 2002; 23:735-762.

2. Best K. Experimental male methods inhibit sperm. Network 1998; 18:16-19, 31.

3. Christensen D. Male choice. The search for new contraceptives for men. Science News 2000; 158:222.

4. Anderson RA, Zhu H, Cheng L, et al. Investigation of a novel preparation of testosterone decanoate in men: Pharma-cokinetics and spermatogenic suppression with etonogestrel implants. Contraception 2002; 66:357-364.

5. Gonzalo IT, Swerdloff RS, Nelson AL, et al. Levonorgestrel implants (Norplant II) for male contraception clinical trials: Combination with transdermal and injectable testosterone. J Clin Endocrinol Metab 2002; 87:3,562-3,572.