Is male contraceptive on horizon? Trials under way

Look for new developments this year when it comes to male contraception. While it may be some time before an actual product reaches the market shelves, scientists are gaining ground in the development of possible forms of birth control for men.

Schering AG of Berlin, Germany, and Organon International of Oss, the Netherlands, are conducting a double-blind, randomized Phase II trial and are enrolling 350 men in 14 centers throughout Europe. The study will evaluate six dose combinations of etonogestrel in implant form and testosterone undecanoate in injection form. At the present time, no U.S. center is included in the trial, says Schering spokeswoman Astrid Forster.

"We will expand the study concept to the United States if we get positive results and have decided to do a further trial," says Forster.

According to Schering, Phase III studies to investigate the long-term efficacy and safety of the method will follow as soon as the current Phase II study has been successfully completed. A marketable product may be available at the latest by 2009, according to the company.

The Geneva-based World Health Organization (WHO) has completed enrollment and is conducting follow-up in a Phase III trial of injectable testosterone undecanoate in China, reports Herbert Peterson, MD, coordinator of the Promoting Family Planning program in the WHO’s Department of Reproductive Health and Research. The WHO initiated a Phase II trial of testosterone undecanoate plus depot medroxy-progesterone acetate (DMPA) in Indonesia in 2002. Study results will be reported this year, says Peterson.

Look at combinations

Research first begun by the WHO indicates that testosterone is effective in suppressing sperm production.1 An excess amount of testosterone inhibits gonadotropins and causes a decrease in natural levels of testosterone in the testes and hampering the manufacture of sperm.2 The WHO’s two-year trial of weekly testosterone enanthate injections showed contraceptive efficacy comparable to those of female hormonal methods, with fertility restored two to three months following the last injection.1

Research indicates that testosterone treatment alone does not reliably suppress sperm production to the point of azoospermia in most men, so scientists have moved their focus to combinations of longer-acting testosterone derivatives and a progestin.3 Such a combination results in suppression of serum gonadotropins and sperm counts; the right mixture is now the main focus of male contraceptive research.3 Testosterone administered in combination with DMPA, norethisterone enanthate, desogestrel, or etonogestrel has shown promising efficacy.4

Australian scientists have looked at one such combination by conducting a study of 55 couples, with the men using testosterone implants and DMPA injections.5 The men underwent the hormone treatment every three or four months to switch off sperm production. Couples relied on the treatment as their only contraceptive. No pregnancies were reported during the study period.5

Who needs male options?

Who would be a suitable candidate for male contraception? Men who wish to be partners in birth control or those with partners unable to use contraception, according to information presented at "New Frontiers in Contraceptive Research," an international symposium sponsored by the Washington, DC-based Institute of Medicine.6

Men are interested in using such new forms of contraception. In a 2002 survey, three-quarters of men said they would consider trying male hormonal contraception.7 The three most popular choices for method of administration included an oral pill, a thrice-monthly injection, or a twice-yearly injection.

As with women, men’s willingness to use hormonal contraception will depend upon effectiveness, convenience of use, and side effect profile.3 Any method that is painful, expensive, inconvenient, requires extensive monitoring, or inhibits sexual function or general health will not be chosen or will be quickly discarded.8

Will women trust their partners to use a hormonal method for contraception? Findings from a multinational survey of women indicate they will. Just 2% said they would not trust their partner to use such a method.8

References

  1. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril 1996; 65:821-829.
  2. Best K. Experimental male methods inhibit sperm. Network 1998; 18:16-19, 31.
  3. McLachlan RI. Male hormonal contraception: A safe, acceptable, and reversible choice. MJA 2000; 172:254-255.
  4. Kamischke A, Nieschlag E. Progress towards hormonal male contraception. Trends Pharmacol Sci 2004; 25:49-57.
  5. Turner L, Conway AJ, Jimenez M, et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab 2003; 88:4,659-4,667.
  6. Bremner W. Male Hormonal Contraception. Presented at the New Frontiers in Contraceptive Research International Symposium. Washington, DC; July 16, 2003.
  7. 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.
  8. Glasier AF, Anakwe R, Everington D, et al. Would women trust their partners to use a male pill? Hum Reprod 2000; 15:646-669.