September 2004, Vol. 10, No. 3

Biomedical Research
Potential Long-Acting Male Contraceptive Studied

Scientists know much more about the basic workings of the female reproductive system than about the male reproductive system. Thus, while for more than 40 years birth control pills and intrauterine devices have been providing highly effective, practical, and acceptable long-term contraception for women, the development of reversible, long-term male contraception has confounded researchers. Much of the work done at the Population Council’s Center for Biomedical Research is geared toward gaining a more complete understanding of male reproductive physiology and developing new male contraceptives. Recent research conducted by Council biomedical researchers and the Council’s International Committee for Contraception Research (ICCR) confirms the promise of MENT^®, the Council’s trademarked synthetic androgen, as a component of a male contraceptive method.

The ICCR, established by the Population Council in 1970, is a network of distinguished scientists and clinical investigators who conduct clinical trials to test the safety, efficacy, and acceptability of Council-developed products.

MENT
Several potential male contraceptive methods that rely on MENT (7α-methyl-19-nortestosterone) are under development at the Population Council. Council researchers identified MENT, a testosterone-like hormone, as a suitable contraceptive candidate because it suppresses the secretion of hormones that stimulate the testis and control reproductive activity. The inhibition of these hormones— including luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone— reduces sperm production. At the same time, MENT replaces testosterone to maintain primary and secondary sex characteristics. An added advantage of MENT is that it does not overstimulate the prostate, as does testosterone. It also maintains libido, an important function of testosterone. MENT is ten times as potent as testosterone. Thus, the doses required are lower than those found in commercially available testosterone preparations, making it feasible to administer the compound via long-acting subdermal implants.

The Council is investigating the contraceptive potential of MENT acetate (MENT Ac), which the body breaks down into active MENT. Thirty-five volunteers were recruited in three clinics, one each in Germany, Chile, and the Dominican Republic. These men were randomly assigned to one of three doses of MENT: one implant (12 men), two implants (11 men), and four implants (12 men). The implants were inserted on the inside of the upper arm. Two men dropped out of the study, one for personal reasons and the other because of high blood pressure. The man’s blood pressure returned to normal within one month of implant removal, after the patient quit smoking and went on a diet. “High blood pressure has not emerged as a problem in larger studies of MENT,” states Population Council scientist Irving Sivin. “We believe that the condition was unrelated to MENT and probably arose due to the patient’s smoking and eating habits.”

The treatment was initially designed to last six months. However, on the basis of early positive findings, the length of the study was extended in two clinics to nine months for the two-implant group and to 12 months for the four-implant group.

Dose-dependent response
The researchers found that the greater the number of implants a man had, the higher the level of MENT in his blood and the lower the levels of testosterone, LH, and FSH. In addition, the more implants a man had, the greater his reduction in sperm production. In eight of the 11 remaining men with four implants, sperm counts rapidly dipped to zero. This condition lasted in many subjects for several months until the implants were removed. After removal, an interval of about three months was required for sperm counts to return to normal in these men. Furthermore, participants at every dosage level reported no significant change during or after treatment in four measures of sexual performance.

“This study demonstrates that MENT Ac, when administered in a sustained-release fashion via subdermal implants, can inhibit the production of sperm over a prolonged period,” says Narender Kumar, Population Council biomedical researcher. “MENT definitely has the potential to be used as a male contraceptive.” Population Council scientists are studying the effect of combining MENT Ac implants with a synthetic progestin hormone. A number of studies have shown greater suppression of sperm production when the androgen is combined with a progestin. Long-term toxicology studies of MENT are also ongoing.

Source
von Eckardstein, Sigrid, Gabriela Noe, Vivian Brache, Eberhard Nieschlag, Horacio Croxatto, Francisco Alvarez, Alfred Moo-Young, Irving Sivin, Narender Kumar, Margaret Small, and Kalyan Sundaram. 2003. “A clinical trial of 7α-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men,” Journal of Clinical Endocrinology and Metabolism 88(11): 5232–5239. (offsite abstract)

Outside funding
The Bingham Trust, the Educational Foundation of America, the Lila Annenberg Hazen Foundation, the George Hecht Family Trust, the William and Flora Hewlett Foundation, the Andrew W. Mellon Foundation, the National Institutes of Health, the United Nations Population Fund, and the United States Agency for International Development

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See Also

• "Biomedicine/Product development," overview (full text)