Safe, effective and reversible alternative contraceptives for men

Most men know when their family is complete, and vasectomy remains the most effective and safest form of sterilization. Around 10% of vasectomized men in the U.S desire vasectomy reversal due to the high divorce rate in this country and other life circumstances.

Now new experiments with macaque monkeys show for the first time that it may soon be possible to produce safe, effective and reversible alternative contraceptives for men.

Those experiments, described in the Nov. 12 issue of the journal Science, involved immunizing fertile male monkeys with a purified recombinant form of Eppin, a harmless protein produced in the testis and epididymis of humans and other primates.

Although they bred, none of the males fertilized female macaques until after researchers discontinued the Eppin. Then, most of the animals succeeded in reproducing again. All remained healthy.

"These results are exciting to us," said Dr. Michael G. O’Rand, professor of cell and developmental biology at the University of North Carolina at Chapel Hill School of Medicine and principal investigator. "Not only do they show that this approach, which is called immunocontraception, works, but they also should renew interest in the subject. Interest in immunocontraception fell off in recent years since scientists had not previously succeeded with it."

UNC Laboratories for Reproductive Biology co-authors of the Science report include research assistant Esther Widgren; Dr. Perumal Sivashanmugam, a former postdoctoral fellow now doing a fellowship at Duke University; Dr. Richard T. Richardson, research associate professor of cell and developmental biology; and Drs. Susan H. Hall and Frank S. French, research associate professor and professor, respectively, of pediatrics. Other authors include Drs. Cathy A. VandeVoort of the California Primate Research Center at the University of California at Davis and A. Jagannadha Rao of the Primate Research Laboratory at the Indian Institute of Science in Bangalore.

"Although several different choices and approaches are available for contraception in women, the choices for men are currently limited to condoms and vasectomy," O’Rand wrote. "Male hormonal contraceptives developed over the past several years have now advanced to clinical trials, and the outcome of these studies may determine whether the suppression of sperm production through androgen regulation can become a realistic product.

"Immunocontraception, an alternative non-hormonal method, has been studied for many years with the major emphasis on immunization of females to prevent pregnancy or fertilization. In the present study, we report the successful contraception of male nonhuman primates…. This represents a non-hormonally disruptive male immunocontraceptive for primates."

When his colleagues in India injected the male monkeys with Eppin, the animals’ immune systems created antibodies to the protein just as they would to disease organisms, O’Rand said. Those antibodies bound to the macaques’ own natural Eppin and prevented fertilization.

Seven of the nine males tested over several years developed high antibody levels, and five of the seven recovered fertility once the immunization stopped.

"We don’t understand the exact mechanism yet, but we think the immunocontraception works by preventing the sperm from freeing itself from the seminal fluid to make its way to the uterus and oviducts to fertilize the egg," he said.

Because human and other primate reproduction is so similar, the researchers know of no reason why the same thing would not happen in men, O’Rand said.

The next step will be to interest government agencies or private companies in funding further research, he said.

"Contraception in general and male contraception in particular can be controversial, and so that will be a hurdle we’ll have to address and overcome," the UNC scientist said. "Certainly, toxicology studies would be necessary. Also, private companies would have to be convinced that they would be able to make a profit on such a product.

"Our feeling right now is that this is an attainable goal and the approach has the potential to become a very important male contraceptive."

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