Nonhormonal method avoids side effects, researchers say
THURSDAY, Aug. 16, 2012 (HealthDay News) -- A hormone-free drug tested in male mice might someday prove viable for men who want their own birth-control pill, according to new research.
The compound stifles sperm production but not sexual activity, fertility returns once treatment stops and males can go on to father healthy offspring, the researchers say.
Strictly speaking, the new drug is not yet a male "pill," explained lead researcher Dr. James Bradner, of the Dana-Farber Cancer Institute and Harvard Medical School in Boston.
"The molecule used in this study, JQ1, is a prototype drug," Bradner said, explaining it is not intended for human use. "We have successfully administered the agent to animals by mouth, but notably in this research, JQ1 was injected into the belly of the mice and rats studied."
JQ1 works by targeting a protein called BRDT that functions in the testes and is vital for fertility. Unlike previous drugs, JQI can physically reach the cells that make sperm. Sperm cell production drops in number and surviving sperm don't work as well.
Researchers injected the rodents over an 18-month period and found they were mating as much as ever, but were completely infertile at higher does of JQ1. After treatment ended, they were again able to sire apparently healthy offspring.
"Mice can only report a few obvious symptoms," Bradner said, "but with that caveat we do not observe any developmental or behavioral effects on offspring."
The results have implications for men as well as mice.
"Humans do indeed have the BRDT gene, and human genetics suggests a similar role for BRDT in sperm production," Bradner said. "We therefore tested activity against the human BRDT protein and found that JQ1 is a highly potent inhibitor of human BRDT."
The study is published in the Aug. 17 issue of the journal Cell.
Diana Blithe, program director for contraceptive development at the U.S. National Institute of Child Health and Human Development, called the new findings "exciting."
"I'm pleased anytime I see something that is completely effective and completely reversible," Blithe said.
Males need more contraceptive options, she said.
"A lot of women are unable to take birth-control pills or use effective methods that are on the market, and if they are trying to avoid pregnancy, they need help from their partner," Blithe said. "There are an awful lot of men who feel that it's very important for them. From their point of view, they want to share in the responsibility of whether or not they're causing pregnancies to occur."
Blithe cited drawbacks of hormonal types of male birth control being studied.
"The hormonal methods work by a two-step process," she said. "The first is, you use progestin, which inhibits the hormones that cause testosterone to be produced in the testes. If you inhibit the whole cycle and reduce the testosterone in the testes to very low levels, you stop sperm production."
But this also eliminates "the ability to have erections and ejaculations and protect muscle mass and things like that," she added.
The second step is giving men a replacement dose of testosterone, enough to reverse the side effects without kicking in new sperm production.
With the new drug, Blithe said, "by being able to inhibit sperm production without impacting any levels of testosterone, you're not having any adverse effects on the animal's ability to have sexual function. Therefore, there would be no need for a replacement dose of a [male hormone]."
The researchers note that studies in animals often fail to provide similar results in humans, and this new form of birth control won't be ready for humans in the near future.
"The development of a drug-like derivative of JQ1 will require at least a few years of dedicated chemistry and biology, though we may derive early insights from cancer clinical trials of structurally similar agents," Bradner said.
Blithe agreed. "This is an indication of an incredibly promising lead from a really talented group of investigators," she said. "I think it represents one of several opportunities and targets and agents that we have identified that could work as a male contraceptive."
However, she added, "it's going to be many years before we see anything that could approach a product on the market because the level of safety for developing a contraceptive is very, very high. You're giving it to healthy people for a very long period of time ... [so] you have to have a product that's very effective and not going to cause side effects."
Visit the U.S. Centers for Disease Control and Prevention to learn more about contraception ( http://www.cdc.gov/reproductivehealth/unintendedpregnancy/contraception.htm ).
SOURCES: James Bradner, M.D., instructor in medicine, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, Boston; Diana Blithe, Ph.D., program director, contraceptive development, U.S. National Institute of Child Health and Human Development; Aug. 17, 2012, Cell