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Progress Toward a Male Contraceptive

An effective contraceptive for men would make a welcome new family planning option. Researchers report that male rats given an experimental new treatment became infertile within four weeks, and that the effect was reversible. The accomplishment might lead researchers to a safe and effective contraceptive for men.

During sperm development, sperm precursor cells adhere to specific cells in the testes as they develop into sperm. A research team led by Dr. C. Yan Cheng of the Population Council's Center for Biomedical Research set out to develop a male contraceptive by trying to disrupt this connection. Their work was supported by grants from NIH’s ×îÐÂÂ鶹ÊÓƵ Institute of Child Health and Human Development (NICHD) and the Consortium for Industrial Collaboration in Contraceptive Research.

The team previously identified a molecule called Adjudin that, when given orally to rats, led to the loss of their sperm precursor cells. Unfortunately, giving Adjudin orally also caused serious side effects, such as liver damage and muscle atrophy, in some of the animals. The team thus set out to see if they could develop a way to target the compound to the testes. They used a molecule called follicle-stimulating hormone (FSH), which is a hormone made by the pituitary gland that stimulates the testes to make sperm. The researchers modified FSH to remove its hormonal activity. They then chemically linked Adjudin to the modified FSH to target it to the testes.

In the October 29, 2006, online edition of Nature Medicine, the researchers show that virtually all the rats’ spermatids, the cells that develop into sperm, were gone by four weeks after injection with the targeted treatment. In mating experiments, all the rats receiving the treatment were infertile within four to six weeks after treatment. Half of the rats regained their fertility by 12 weeks. By 20 weeks, fertility was restored in all the rats, showing that the treatment was fully reversible. Other organs such as the kidney, liver and small intestine weren’t affected by the targeted treatment.

The dose of this treatment needed to make rats infertile was considerably lower than the doses used with Adjudin alone. Also making the compound safer is that it’s delivered specifically to the testis, bypassing other organs. However, while this research is a promising proof of concept, there are still serious technical hurdles to overcome before it could potentially be developed into a commercial product. The researchers are now working to lower the cost of making the compound and to develop better ways to deliver it.

NICHD-funded researchers are also pursuing other strategies to develop a male contraceptive. They hope one of them will eventually lead to a safe, effective, reversible contraceptive for men.