Researchers Closer to Contraceptive for Men : Synthetic Drug Found to Block 2 Hormones Tied to Testosterone and Sperm Production

In the first such study using humans, a team of Nashville researchers working toward the development of a male contraceptive has found a way to decrease the production of testosterone, the principle male hormone, a physician said Thursday.

The research team from Vanderbilt University injected men with a synthetic drug that indirectly blocked the release of two hormones from the pituitary gland that control the functions of the testicles, including the production of sperm and testosterone, said Dr. Spyros N. Pavlou, assistant professor of medicine.

While previous studies with animals have been successful, “this is the first proof it works in man,” Pavlou said in an interview at the international meeting of the Endocrine Society at the Anaheim Convention Center.

Endocrinologists study hormones and other secretions and their effects on the body’s organs.

Shut Off the Testes

The synthetic drug resulted in such a drop in testosterone it effectively “shut off the testes” during the short-term study on nine men, Pavlou said. If the drug eventually were to be used as a contraceptive, it would have to be followed by an offsetting dose of testosterone to restore sexual desire and function.

In addition, he said, it appears that when the drug is stopped, normal testosterone production resumes. “It is a 100% reversal,” Pavlou said.

Testosterone and sperm are produced after a chain of hormonal reactions, which begins with the release of a hormone called “luteinizing hormone releasing hormone” (LHRH) in the brain. LHRH controls the release of two hormones from the pituitary gland.

The hormones, called gonadotropins, travel through the bloodstream to the testicles. There, they regulate the functions of the testes, which manufacture testosterone and sperm, Pavlou explained.

The synthetic drug cancels the effect of the LHRH, effectively preventing the LHRH from carrying their message to to the testes, Pavlou said.

Three Injections

The male volunteers were given three injections, all at least seven days apart. After each injection they were tested for testosterone and gonadatropin levels, which dramatically declined, Pavlou said.

No sperm counts were taken in the volunteers because it takes one to three months for sperm production to be affected, he said. However, the researchers suspect that if the drug is given for longer periods of time, “it will shut off the sperm,” he said. Longer-term studies are planned, he said.

The effect of the injections shut down the volunteers’ sexual functions, “but for two days in the hospital, people didn’t complain,” Pavlou said.

The only disagreeable side effect suffered by the men in the study was a bee sting-like irritation where the drug was injected, he said.

Daily Injections

The researchers also are looking at different ways to administer the LHRH antagonist because daily injections, they realize, are not feasible. One method might be with a nasal spray, with the agent being absorbed through the mucous membranes, he said. Another method might be an injection, good for three months, of time-release beads of the substance. The dose of testosterone could also be given the same way, he said.

In another contraceptive-related study presented at the convention, a group of Australian scientists announced that they have measured levels of inhibin, an elusive reproductive hormone that indirectly controls both egg and sperm production, in human blood.

Hypothetically, inhibin, when given to animals or humans, will shut off the pituitary gland’s production of hormones that stimulate the ovaries to produce eggs and the testes to manufacture sperm, said David de Kretser, a professor at Monash University, Melbourne. It has a “potential” as a future male contraceptive but that is many years away, he said.

“The biggest problem is to get sufficient quantities of it,” just for research, de Kretser said in an interview.

Cannot Be Isolated

Inhibin, a natural hormone, is produced only in trace amounts in the body and cannot be isolated in sufficient quantity for commercial applications, according to the team of researchers from Prince Henry’s Hospital, Monash University and St. Vincent’s Institute of Medical Research, all in Melbourne. Their ability to measure inhibin in human blood is a step toward learning more about the hormone, de Kretser said.