Hormone-blockers may yield male 'pill.' (developing gonadotropin-releasing hormone as a contraceptive)

A troubling side effect has long stymied the search for a male contraceptive drug. Shutting off testosterone, the male hormone that spurs sperm production, can shut down a man's love life as well, because men lacking the hormone often can't get or keep an erection. Now, a research team may have overcome this hurdle. By combining a novel hormoneblocker with testosterone, they completely -- and reversibly -- thwarted sperm production in a small group of volunteers, without robbing the men of their sex lives.

The researchers, led by Laurie Tom of the Harbor-UCLA Medical Center in Torrance, Calif., targeted gonadotropin-releasing hormone (GnRH), a mastercontrol hormone secreted by the brain's hypothalamus. GnRH initiates the sex-hormone production cascade in both men and women.

In men, GnRH turns on two pituitary hormones--follicle-stimulating hormone and luteinizing hormone -- responsible for priming sperm-producing cells in the testes and stimulating testosterone, which initiates sperm production.

Tom and her colleagues gave daily injections of a modified, inactive form of GnRH to eight healthy men over a period of 16 weeks. The modified GnRH "antagonist" was designed to block the men's own GnRH from binding to its receptors, thus preventing the sperm production. The researchers also gave the men testosterone injections every two weeks, which allowed them to get erections.

After 10 weeks, seven of the eight men had no sperm in their ejaculate, although their sexual abilities were otherwise normal, Tom's group reported last week in Washington, D.C., at the annual meeting of the Endocrine Society. Two weeks after the men stopped taking the shots, sperm reappeared in their ejaculate, reaching normal levels after 10 to 14 weeks. The eighth man quit the study because he developed welts at the injection sites.

Tom says her group's study shows that GnRH antagonists could lead to an effective male contraceptive drug. But, she acknowledges, "what needs to be done is to develop a long-acting form," so the drug could be taken less often or orally.

"GnRH antagonists will be the male contraceptive within the next 10 years," predict Spyros Pavlou, an endocrinologist at Vanderbilt University in Nashville. Several years ago, Pavlou tested a larger dose of the same GnRH antagonist used by Tom's group, together with a smaller dose of testosterone, but the combination did not halt sperm production in his volunteers.

Pavlou reported to the Endocrine Society that a different GnRH antagonist alone suppressed levels of the follicle-stimulating and luteinizing hormones in all of 16 men, none of whom dropped out of the study because of side effects. He plans next to test the compound on a larger number of men to demonstrate whether the suppressed hormone levels block sperm production.