Sep. 25, 2000 WINSTON-SALEM, N.C. - Reduced estrogen levels due to stress may put some young women on a high-risk course for heart disease, reported researchers from Wake Forest University Baptist Medical Center today at a meeting of the North American Menopause Society.
"Our study of female monkeys indicates that stress affects estrogen levels and can lead to the development of heart disease - even before menopause," said Jay Kaplan, Ph.D., professor of comparative medicine.
Kaplan said the 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 buildup of fatty deposits in the arteries that can lead to heart attacks and strokes.
"This research demonstrates that a deficiency of estrogen before menopause places these females on a high-risk trajectory, regardless of whether they get estrogen treatment after menopause," said Kaplan. "Our data and recent trials in humans suggest that the emphasis in this country on postmenopausal estrogen treatment may be misplaced."
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 got 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.
"Applied to women, this lifetime study suggests that having an estrogen deficiency in the pre-menopausal years predicts a higher rate of heart disease after menopause, even when treated with hormone replacement therapy after menopause," said Kaplan.
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 points 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.
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