Pumping Up Arteries: Estrogen shows beneficial effect (Estrogen replacement therapy)
Authors: Aschwanden Christie 
Published: August 2003

Hormone replacement therapy's power to cool hot flashes and bolster bone has earned it a reputation as a youth-sustaining pill for postmenopausal women. Scientists have long reasoned that it could help fight heart disease too, in part because premenopausal women have a much lower incidence of the condition than men do; during menopause, estrogen concentrations plummet and the risk for women begins to catch up to that for men. However, a long-term study on a large group released this year--the Heart and Estrogen Replacement Study (HERS)--found that hormone replacement therapy didn't reduce the risk of cardiovascular disease, casting doubt on its benefits in this realm of health care. Now, Mullick and colleagues add fuel to the debate by demonstrating that estrogen protects the vascular system even after treatment stops--at least in rats. What's more, the work lends support to a possible mechanism for the newfound cardiovascular benefits.

The researchers had previously found that estrogen protects arteries from age-associated damage. To probe whether this benefit persists after treatment, they implanted pellets that released either estrogen, progesterone, both, or nothing into 26 Sprague-Dawley rats whose ovaries had been removed so they wouldn't churn out estrogen and progesterone. A fifth group received no implant. After 12 months of hormone treatment, the researchers took out the pellets and allowed 1 month for the hormones to wash away. They then excised the carotid arteries from each rat and measured two indicators of vascular health: arterial stiffness and permeability--the ease with which a test substance seeps through the blood vessel lining. Stiff arteries are associated with high blood pressure because the rigid vessels can't expand properly, and increased permeability promotes the development of atherosclerosis by allowing lipids to more easily penetrate and accumulate in the vascular wall.

Estrogen treatment led to a 34% improvement in flexibility, measured by the arteries' ability to expand with increasing pressure. And estrogen or a combination of estrogen and progesterone blocked passage of a fluorescent test molecule called TRITC-dextran through the artery wall: Only 64% as much of the compound permeated these vessels as it did those subjected to the other treatments.

Previous results suggested that estrogen prevents vascular stiffening by limiting harm from so-called advanced glycation end products (AGEs), which arise from reactions between glucose and proteins and are thought to irrevocably alter proteins and thwart their functions. To find out whether the hormones in this study could be acting by limiting AGE-induced damage, the investigators assessed concentrations of the AGE pentosidine. Even a month after removal of the hormone pellets, concentrations of pentosidine were 50% lower in arteries from rats treated with either estrogen or a combination of estrogen and progesterone than from rats in the other groups.

Because the researchers stopped the hormone treatments 1 month before taking measurements, the data indicate that estrogen's benefits persist even after therapy ends. Results from the new study need to be confirmed in women, and estrogen-based therapy--even when used to confer well-established benefits--is controversial because it might boost the risk of breast and other cancers. But if the results hold up, they'll add weight to the notion that this type of hormone treatment blocks some of the vascular changes that come with increasing age.

--Christie Aschwanden; suggested by James M. Harper

A. E. Mullick, B. A. Walsh, K. M. Reiser, J. C. Rutledge, Chronic estradiol treatment attenuates stiffening, glycoxidation, and permeability in rat carotid arteries.
Am. J. Physiol. Heart Circ. Physiol.
281
, H2204-H2210 (2001).
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