Women might someday take a drug to avoid the bleeding that comes with the menstrual cycle, a study in rhesus macaque monkeys suggests. Beyond enabling a woman to bypass this aspect of her monthly period, such a drug could treat heavy menstrual bleeding that now makes some women anemic and sometimes requires hysterectomy, surgery to remove the uterus.
The compounds being tested operate differently from birth control pills, which provide steady doses of the hormones progesterone and estrogen and thus prevent the brain from triggering ovulation. Instead, two new substances–called ZK 137 316 and ZK 230 211–have stopped menstrual bleeding in female monkeys by blocking progesterone.
In these macaques, as in women, progesterone induces a build-up of tissue and growth of new arteries on the uterine lining, or endometrium. This thickening creates an environment suitable for implantation of a fertilized egg. If the monthly cycle nears its end without such implantation, the supply of progesterone drops. Then, the new vessels rupture and the support tissue sloughs off in menstrual flow.
A study in the August Human Reproduction finds that monkeys getting either of the two progesterone blockers have much less buildup of tissue and apparently less artery formation on the endometrium, says study coauthor
Robert M. Brenner, an endocrinologist at the Oregon Regional Primate Research Center in Beaverton.
Consequently, Brenner says, there is little or no menstrual bleeding in these rhesus macaques, a species whose 28-day monthly ovulation cycle closely resembles that of people. After being taken off the drugs, monkeys in both groups returned to having normal menstrual cycles within 15 to 41 days, Brenner and his colleagues report.
This study “is first-rate quality,” says endocrinologist David H. Abbott of the University of Wisconsin-Madison. “I see huge potential [in these drugs] for women with heavy bleeding, endometriosis, and really bad PMS,” or premenstrual syndrome, he says.
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Endometriosis, the growth of endometrial tissue in abnormal locations, is painful and can require surgery. Severe PMS can cause irritability, fluid retention, headaches, and other symptoms.
The two experimental drugs differed slightly in their effect. Monkeys getting ZK 230 211 didn’t ovulate, whereas some animals getting ZK 137 316 did. Maintaining normal ovulation might be preferable because the estrogen produced would preserve a woman’s bone strength and benefit her heart, Abbott says.
The drugs work by binding to progesterone receptors on the surface of cells.
In this way, ZK 137 316 and ZK 230 211 prevent the normal progesterone-induced cascade of biological events, Abbott says.
While these drugs may offer several potential benefits for women, they also might carry risks, he says. For example, a drug that inhibits a buildup of the uterine lining even as it permits ovulation could result in miscarriage if a fertilized egg implants in a weakened lining. “I would see this drug coming with a warning” against trying to become pregnant during its use, Abbott says.