A more than three decades' hunt for safe and effective male birth control pills is now coming to an end. The experimental study on the new pill known as DMAU or dimethandrolone undecanoate is expected to revolutionize suppression of hormones responsible for sperm production.

Leading researchers from National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the funding institute for the study, showcased the groundbreaking findings on DMAU in a recent Chicago press conference.

According to the Stephanie Page, MD, PhD, professor of medicine at the University of Washington, Seattle, Washington and the senior investigator of the study, the experimental male oral contraceptive works just like the pill for women. DMAU combines activity of an androgen (testosterone) and a progestin and is taken once a day for 30 consecutive days.

One hundred men between the ages of 18 to 50 were enrolled in the study at the University of Washington Medical Center and at Harbor-UCLA Medical Center in Torrance, California. However, only 83 men were able to complete the study from start to finish. The experiment entailed giving blood samples for hormone and cholesterol testing,

"DMAU is a major step forward in the development of a "once-daily male pill'," Page said. "Many men say they would prefer a daily pill as a reversible contraceptive, rather than long-acting injections or topical gels, which are also in development."

The Male Contraceptive Experiment

Three different doses of DMAU in 100, 200, and 400 milligrams, added with castor oil and powder formulation in the capsules were tested. More than 40 subjects were randomly assigned to each dose group of 100, 200, and 400. Each dose group had five subjects who received inactive placebo, the remaining 12 to 15 men received DMAU. The men who took either the drug or placebo once a day for 28 days were given food because DMAU is effective when taken with food.

A dose of 400 mg DMAU switched off the male volunteers' testosterone and two other hormones responsible for sperm production. The study noted that the low levels of these hormones were consistent with effective male contraception in longer-term studies.

Very few subjects with low levels of testosterone in their system reported symptoms of testosterone deficiency. However, all groups taking DMAU reported weight gain and decreased good cholesterol. In general, all men were subjected and passed the safety test for their livers and kidneys.

Page emphasized that results are unprecedented and promising in the development of a prototype male pill and that longer-term studies are currently underway to confirm that DMAU taken every day blocks sperm production.

Meanwhile, Diana Lynn Blithe, PhD, NIH director of the Contraceptive Development Research Center Program and Male Contraceptive Development Program explained that the study was confronted with challenges but giant steps were so far achieved.

Blithe compared the process in the development of female and male contraceptives. The female contraceptives involved a safety test of over 20,000 menstrual cycles with around 400 women using the method in a one-year assessment. However, the road to the development of male contraceptives was far from laid on the line.

She added that risk-benefit situation in men is harder to calculate simply because they do not bear the risk of pregnancy or childbirth. So far, men are already using contraceptive methods such as vasectomy, but this said method is irreversible and cannot be completely relied on as effective.

When asked about other methods being explored, Blithe said that there are other methods of male contraceptives being studied including non-hormonal methods such as bromodomain inhibitors and a retinoic acid pathway. "Bromodomain proteins are known to regulate apoptosis, migration and evasion in cells. Also being looked into is BRDT, a testis-specific inhibitor of a bromodomain involved in spermatogenesis to reversible contraceptives, " said Blithe.

Spermatogenesis is known as the production or development of mature sperms in men.

In addition, the team is also investigating other hormonal methods of preventing spermatogenesis. Trials showed topical gel composed of progestin and testosterone fully suppressed sperm production by 90 percent among trial participants. The topical gel was used every day for three months. The effects of the gel are also reversible and can be stopped at any time should partners decide to have a child.

DMAU Pill vs. Predecessors

Since 1961, scientists have tried and tested forms of testosterone but only resulted in liver inflammation among men. These oral forms required two doses a day to be effective in the body. However, DMAU was able to overcome these limitations because it contains a long-chain fatty acid called undecanoate which slows down clearance of the hormones in the body. Thus, one pill a day is enough. In addition, DMAU is found safe, effective, and does not affect male sex drive.

In the 1950s, another compound known as BDADs was explored as a possible male contraceptive. Unfortunately, the resulting agent had serious side effects. Other trials on male contraceptives administered through injections or gels also showed risks on the liver. Compared to DMAU, the results of the month-long study are promising with no damage on the liver. Furthermore, the once-a-day DMAU pill version comes handy and is easier to take for men busy with life and career.

[researchpaper 리서치페이퍼= Kay Yeban 기자]