Sci. Aging Knowl. Environ., 13 October 2004
Progestin siblings exert opposite effects on monkey hearts
Like fraternal twins, two versions of the same hormone behave quite differently. New research in monkeys shows that the progestin most commonly used in hormone replacement therapies in the United States contributes to heart damage, whereas a version more commonly found in European countries does not. The results highlight how little researchers know about these drugs and their effect on women's physiology.
Most hormone replacement therapies (HRT) for women undergoing menopause alternate two compounds: estrogen, the hormone that regulates egg maturation, and progesterone, the hormone that sustains pregnancies. Studies that examine HRT's ability to protect women from postmenopausal symptoms such as thinning bones and heart disease use different combinations of synthetic estrogen and synthetic progesterone, also called progestin. However, several versions of progestin with slightly different chemical structures are on the market. The largest U.S. study, the Women's Health Initiative, chose the progestin typically prescribed by American doctors, MPA (sold under the brand name Prempro), and found that the therapy increased the risk of heart attacks and strokes. As a result, many doctors and patients have discontinued HRT. But some experts have noted that the study probed only one hormone concoction, and other formulations might avoid the harmful side effects (see "Weathering the HRT Storm"). All progestins simulate the portion of the menstrual cycle that supports pregnancy, but the different versions exert different effects on other physiological activities. Williams and colleagues decided to compare MPA to another progestin, NETA (sold under the brand name Femhrt), in monkeys that were surgically propelled into menopause. Past studies that compared progestins side by side often varied the type of estrogen as well, obscuring the effects of the various progestin formulations. To avoid this problem, the researchers treated all animals with the same estrogen, estradiol.
The team removed the ovaries from monkeys whose diet promotes hardening of the arteries. This surgery mimics menopause because the animals no longer produce estrogen. After 2 months, the researchers put each animal on one of three regimes. Fifteen monkeys received no hormones, 12 got estradiol and MPA, and 12 received estradiol and NETA. After 1 year, the researchers simulated a heart attack in the primates by briefly obstructing the artery that delivers blood to the heart muscle. Four hours later, they assessed tissue injury. Animals that received no supplementary hormones suffered damage to 20% of the muscle. The attack mangled 32% of the muscle in the MPA group, but only 2% in the NETA group.
"The result tells us we're dealing with drugs that have different actions," says reproductive endocrinologist Wulf Utian of Rapid Medical Research Inc. in Cleveland, Ohio. "Progestin is not progestin is not progestin." The study indicates that researchers need to closely analyze the hormones and how they influence women's physiology. Clarifying the behavior of the different members of the progestin family might help scientists better coordinate hormonal activities for women's benefit.
October 13, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150