The Estrogen Factor

The most obvious difference between heart disease rates in men and women-the coronary "grace period" women enjoy prior to menopause-may also be the source of the greatest misunderstanding. Noting the spike in heart disease rates after menopause, researchers have assumed, logically enough, that the dropoff in circulating estrogen levels was responsible.

But logic can be a most unreliable guide to human physiology. Can women indeed thank estrogen for their youthful immunity to heart disease, or is it some chemical component of the hormone that deserves credit?

The case for estrogen is compelling, but not yet complete. Nearly every study done to date-most notably, a Harvard Public Health Study indicates supplemental estrogen protects postmenopausal women against coronary heart disease, but none of these studies was the kind of randomized, controlled trial that is the scientific gold standard. Estrogen is believed to boost a
woman's levels of HDL (the so-called "good" cholesterol) and lower her levels of LDL (the "bad" cholesterol), slowing the process of atherosclerosis. It is also thought to make blood-vessel walls dilate more easily, so blockages are less common.

Among the researchers exploring the artery-friendly powers of estrogen is Frank Sacks, associate professor in the Department of Nutrition. "Estrogen increases the rate at which LDL is removed from the bloodstream," says Sacks. "Our work is focused on the basic, metabolic process by which this happens."

Previous research has found that estrogen increases the number of LDL "receptors" deployed on the surface of liver cells. These receptors, which bind specifically to LDL molecules, enable the liver to filter LDL out of the blood. Sacks has built on this work by showing that estrogen also increases the body's production of HDL, thereby preventing cholesterol buildup in arteries. "A better understanding of this process may one day lead to estrogen-based treatments for lowering high cholesterol counts,"Sacks comments.

Has evolution rigged the heart disease equation against men-endowing women with heart-healthy estrogen and men with testosterone, which has been shown to lower levels of beneficial HDL. "Heart disease was irrelevant in evolution," Sacks remarks. "Few people lived long enough to be affected by it. Testosterone helps build muscles; the fact that it could promote heart disease later in life didn't matter much." Estrogen, on the other hand, "plays a beneficial role during pregnancy by stimulating fat metabolism and helping women put on weight."

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