WINSTON-SALEM, N.C. - Reduced estrogen levels due to stress could put some young women on a high-risk course for heart disease, reported Jay Kaplan, Ph.D, from Wake Forest University Baptist Medical Center today at the American Psychosomatic Society Annual Meeting.

"Observations of female monkeys show that stress during the years before menopause can lead to the early development of hardened arteries," said Kaplan, professor of comparative medicine. "Applied to women, this suggests that having an estrogen deficiency in the pre-menopausal years predicts a higher rate of heart disease after menopause."

Kaplan said that women have traditionally been considered "immune" from heart disease until after menopause, when their estrogen levels dramatically drop. His research showed that stress can actually reduce estrogen levels much earlier in life and cause the early development of hardened arteries that can lead to heart attacks and strokes.

"This research demonstrates that stress can contribute to blood vessel disease, a long-standing hypothesis previously supported by little direct evidence," said Kaplan.

In the study, female monkeys were placed in groups so they would naturally establish a pecking order from dominant to subordinate. Monkeys that were socially stressed - because they were in subordinate roles in their group - produced reduced amounts of the hormone estrogen. In women, the estrogen produced before menopause helps protect against heart disease and osteoporosis.

Kaplan's results showed that the estrogen-deficient monkeys had four times more atherosclerosis than dominant monkeys that produced normal levels of estrogen. When the subordinate, or "stressed," monkeys received estrogen treatments either before or after menopause, their rates of atherosclerosis were cut in half. When they got a "double dose" of estrogen - both before and after menopause - their rates of atherosclerosis were equal to the dominant monkeys.

An ongoing study of human autopsy results supports Kaplan's findings. Results released last year showed that by age 35, one-third of women have substantial atherosclerosis in the vessels leading to their hearts.

In women, stress, anorexia nervosa and hormone imbalances can all reduce estrogen levels to the point that menstrual periods stop. But Kaplan and colleagues theorize that more moderate drops in estrogen - that don't produce symptoms - can also affect health.

"We know from monkey studies that stress can lower estrogen levels to the point that health is affected, even though the animals still have menstrual periods," he said.

In a study of 66 women having normal-length menstrual periods, estrogen levels were low enough in half of the participants to cause the bone loss that can lead to osteoporosis. Kaplan theorizes that if reduced estrogen levels can cause bone loss in women, they can also cause atherosclerosis.

In Kaplan's monkey study, estrogen was given in the form of oral contraceptives prior to menopause. After menopause, it was given as hormone replacement therapy. Monkeys were selected for the study because they closely resemble humans in behavioral and reproductive characteristics. The cynomolgus macaques, used in the study, have a 28-day menstrual cycle and the females (except stressed subordinates) have a natural resistance to heart disease compared to males. The research was funded by the National Heart, Lung and Blood Institute.

---Wake Forest University

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