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Advantages of HRT in perimenopause

December 14th 2005

Recent research in monkeys at the Wake Forest University
Baptist Medical Center in North Carolina suggests that the perimenopause, the
stage when the function of the ovaries is changing, is a critical time for
preventing heart disease and osteoporosis. This was revealed by Professor Jay
Kaplan of the hospital's school of medicine when he addressed the annual meeting
of the American College of Veterinary Pathologists in Boston
"Research in animals suggests that the five years before menopause are
when bone is lost and when heart vessel disease begins to accelerate," he
said, "and waiting until menopause is not the time to start thinking about
prevention."
Kaplan, a professor of comparative medicine, was invited to summarise 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
oestrogen 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
oestrogen levels. It is a time of increased vulnerability to chronic disease."

It has been widely believed that women are almost immune from heart disease
until after menopause, when their oestrogen 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 oestrogen levels and lead
to the build up 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 oestrogen before
menopause places these females on a high-risk trajectory, even if they got
oestrogen treatment after menopause."


For women in perimenopause who intend to take hormone therapy, Kaplan said
the research suggests that this may be the best time to start. "The results
emphasise that primary prevention of heart disease should start pre-menopausally," he
said.

Kaplan's animal studies found that treating the oestrogen-deficient monkeys
with oestrogen before menopause markedly slowed the growth of atherosclerosis.
Kaplan said the findings were consistent with the hypothesis that oestrogen
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 oestrogen
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 doctors 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 (oestrogen and progestogen) increased risk of breast cancer, heart
attacks and stroke. As a result of the study, many doctors advise that women
do 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.


It has been believed for some time now that if oestrogen is started early
enough in the perimenopause, it could yet be proven to be beneficial for both
the heart as well as the bones. The surprising results of risks of HRT shown
in the WHI trial can be explained by the fact that many women in this trial
were starting HRT several years after the menopause when damage to blood vessels
may have already occurred. Of course this latest information from animal studies
cannot be directly applied to women but results of the trial of HRT in perimenopausal
women are eagerly awaited. Meanwhile, women can be reassured that use of HRT
in the early menopausal and perimenopausal years, when it is most often used
for controlling menopausal symptoms, is very unlikely to be harmful for the
heart and may in fact be beneficial.

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