Finally, 'The Pill' for men?

Researchers working together from around the country have identified a compound originally intended to treat cancer that may well become the first male contraceptive agent.

The compound, known as JQ1, makes male mice reversibly infertile without hampering sex drive, altering hormones, or inhibiting future production of healthy offspring, according to a study appearing in the journal Cell.

One of the biggest challenges to developing a male “pill,” according to experts, has been finding an agent that crosses the blood:testis barrier and reaches the area where sperm are produced. A small-molecule inhibitor, JQ1 does so by targeting a testis-specific protein called bromodomain (BRDT).

When male mice are given JQ1, according to the study’s authors, they produce fewer sperm, and those they do produce have reduced motility. In fact, the researchers reported that after 6 weeks of daily injections with the agent, mice sperm counts were down nearly 90%. And only 5% of the remaining sperm were properly motile, compared with 85% in the control mice. After 3 months of treatment, none of the male mice could reproduce, even though mating behavior appeared normal.

All of the males could once again produce offspring between 1 and 3 months after stopping the treatment without any adverse consequences on testosterone or other hormone levels, sexual behavior, sperm count/motility, or the ability to produce healthy offspring. None of the male mice had noticeable side effects, and offspring appeared normal.

The compound was originally developed to target a protein called BRD4, which regulates cell division and is involved in a type of aggressive skin cancer. In fact, the agent is also showing promise in treatment of leukemia, multiple myeloma, and lung cancer.

The compound isn’t ready for testing in humans, but because human and mouse BRDT proteins are so similar, the researchers fully expect that their discovery will one day result in an effective male contraceptive.

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