Researcher Closing In On Birth Control Pill For Men

June 18, 1997

It's often been said that love is blind.

Now a scientist is hoping that he has found a way to apply that old saying to a new method of family planning.

Joseph Hall, a biochemist at North Carolina State University in Raleigh, is unlocking the secrets of sperm, and closing in on a possible birth control pill for men.

The scientist, whose research is supported by the National Science Foundation's division of integrative biology and neuroscience, has taken the next step in his quest to develop a male contraceptive. Hall has recently developed a synthetic chemical compound that "blinds" sperm. "I've worked on this for more than ten years," he says, "and now I feel that we're getting close to identifying a beginning point for sperm-targeted contraceptive development."

Hall found that the compound, a sugary substance, inhibits 98 percent of the enzymatic activity needed for sperm maturation and fertility in male rats, without altering their hormonal balance. He's now testing the compound on bull and human sperm, with results thus far "very promising." A patent application has been filed on the sugar analog, and on two similar compounds.

"The sugar analog appears to have a short onset of action, negligible effects on the libido, and no residual effect on fertility after the dosage has been discontinued," says Hall.

His analog works by inhibiting the activity of the 'B' form of the N-acetyl-beta-D-hexosaminidase enzyme, which is secreted and inserted into sperm cells after they leave the testis, where they are created. They then move into a long, tubelike organ called the epididymis. The analog gives sperm cells the ability to recognize, bind with and penetrate egg membranes, resulting in fertilization. The enzyme's two variant forms, 'A' and 'B,' perform the same physiological function. But the main difference, explains Hall, is that while both forms are found in all other cells, sperm cells contain only the 'B' type.

"The 'B' variant gives sperm its 'eyes,' so to speak," he says. "When you inhibit it, you essentially create blind sperm that cannot recognize eggs. But because you're not inhibiting the 'A' variant, you're not preventing the enzyme from performing its necessary physiological function in the rest of the body."

In addition to in vitro (test tube) experiments on rat sperm, which show that the analog inhibits 98 percent of the enzymatic activity required for egg recognition, Hall also has demonstrated that his analog blocks fertilization by about 90 percent when given to rats orally, or in vivo.

"However, we do not fully understand if the same mechanism that occurs in vitro also occurs in vivo, since we have not yet performed experiments to determine how the compound is metabolized," he explains.

Additional work will be needed before scientists can know for sure whether the analog is safe and effective on humans, but Hall's recent discoveries take researchers one step closer to a male contraceptive.

Most research, up to this point, has focused on chemical or endocrinologic manipulation of sperm in the testis, he says, which studies have shown can cause hormonal imbalances and other undesirable side effects. "By targeting sperm after it has reached the epididymis, we don't have to mess with male hormones at all."

Hall is a father of six. Early in their marriage, when Hall and his wife discussed contraception as a young couple, there were relatively few options available. His wife challenged him to develop a safe, effective male birth control pill. If current results are any indication, he's well on his way to meet the goal.
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National Science Foundation

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