Perimenopause is a Critical Time for Health

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Research in monkeys suggests that the perimenopause – the five to 10 years before a woman’s menopause – is a critical time for preventing heart disease and osteoporosis.

“Research in animals suggests that the five years before menopause are when bone is lost and when heart vessel disease begins to accelerate,” according to Jay Kaplan, Ph.D., from Wake Forest University Baptist Medical Center, who spoke today at the annual meeting of the American College of Veterinary Pathologists in Boston. “Waiting until menopause is not the time to start thinking about prevention.”

Kaplan, a professor of comparative medicine, was invited to summarize his extensive research on how hormone levels affect health. His work has focused primarily on how stress during the younger years can interfere with ovulation and reduce estrogen levels, which can set the stage for heart disease later in life.

"But, this isn’t just a problem in younger women,” he said. “At perimenopause, all women are affected by variably changing and ultimately declining estrogen levels. Perimenopause is a time of increased vulnerability to chronic disease.”

Women have traditionally been considered immune from heart disease until after menopause, when their estrogen levels dramatically drop. However, Kaplan’s research has shown that in monkeys, the process starts much earlier. He found that stress in the younger years can reduce estrogen levels and lead to the buildup of fatty deposits in the blood vessels (atherosclerosis) that can lead to heart attacks and strokes.

“Our research adds to the growing body of evidence that cardiovascular health after menopause is influenced by hormone levels many years earlier,” said Kaplan. “Our monkey studies showed that a deficiency of estrogen before menopause places these females on a high-risk trajectory, even if they got estrogen treatment after menopause.”

For women in perimenopause who intend to take hormone therapy, Kaplan said the research suggests that perimenopause may be the best time to start.

“The results emphasize that primary prevention of heart disease should start pre-menopausally,” he said.

Kaplan’s animal studies found that treating the estrogen-deficient monkeys with estrogen before menopause markedly slowed the growth of Atherosclerosis. Kaplan said the findings were consistent with the hypothesis that estrogen inhibits the development of vessel disease, but may be ineffective if the disease already exists.

“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.

Kaplan said that some physicians advocate women taking oral contraceptives right up until menopause, and then beginning hormone therapy. He said animal research suggests that oral contraceptives can be effective in heart disease protection.

However, the Women’s Health Initiative, the largest study to date to test the effectiveness of hormone therapy in women, found that treatment with combination therapy (estrogen and progestin) increased risk of breast cancer, heart attacks and stroke. As a result of the study, many doctors advise that women not take hormone therapy to prevent heart disease.

But critics of that study say it didn’t involve enough younger women to see if taking the drugs earlier can be effective for prevention. A theory that there is a “window of opportunity” for hormone therapy to be effective for prevention is being tested in a five-year study of peri-menopausal women ages 45 to 54. Funded by the Kronos Longevity Research Institute, the study is evaluating an oral tablet containing estrogen, a skin patch delivering estrogen and a placebo.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. The system comprises 1,187 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of “America’s Best Hospitals” by U.S. News & World Report.

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