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A systematic Medline search using “menopause” and “hormone
replacement therapy” was performed in March 2007, which
was limited to human subjects and articles from journals in English language.
The American College of Obstetricians and Gynecologists Women’s
Health Care Physicians have published guidelines on their website
at http://www.greenjournal.org
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Menopause is defined by 12 consecutive months without menstrual
periods; it naturally occurs between 45 and 55 years of age. Women
experience variable symptoms during the perimenopausal period and
frequently seek advice from their health care provider regarding
the short- and long-term management of the changes related to menopause.
For many years, the mainstay of menopausal treatment has been estrogen
alone or in combination with progesterone. Hormone replacement therapy
was thought to be beneficial in women in preventing heart disease.
In the last decade, the approach to treatment of menopause has changed
as findings from randomized, controlled clinical trials have shown
detrimental effects of estrogen on breast cancer and no improvement
in cardiovascular outcomes. Recently, a National Institutes of Health
State of the Science Panel has recommended only short-term use of
hormone therapy (HT) for menopausal symptom relief and, as such,
used the term menopausal hormone therapy (MHT) rather than hormone replacement
therapy.1 Primary care providers should be familiar with
the available evidence regarding MHT to be able to counsel patients
in the short- and long-term use of MHT. Given the potential risk
related to HT, many patients and providers consider the use of alternative
therapy to treat menopausal symptoms.
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Observational studies reported positive effects with HT in postmenopausal
women in the prevention of chronic diseases, which resulted in the
widespread use of estrogen and progesterone.2 The largest
of these observational studies was the Nurses’ Health Study
that began in 1976 and was renewed in 1993 and 2002.3 It
enrolled over 121000 nurses initially and remains the largest and
longest-running study of women’s health. A 10-year follow-up
of postmenopausal participants, who were taking estrogen and did
not have coronary heart disease or cancer at baseline, showed a
reduction in incident coronary heart disease.3 In 1997,
the Postmenopausal Estrogen/Progestin Interventions Trial
was one of the first randomized trials to demonstrate potential
benefits of HT on surrogate markers for heart disease and osteoporosis.4 This
trial also led to the recommendation of combined estrogen and progesterone
in women with an intact uterus. Until 2001, HT was widely recommended
to prevent cardiovascular disease (CVD).
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In 1998, the Heart and Estrogen/Progestin Replacement
Study (HERS) showed an increase in coronary heart disease during
the first year of HT; among women with established heart disease, there
was no overall CVD benefit compared to placebo.5 Another
surprising result was an increase in the risk of venous thrombosis
in the HERS study.6
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The Women’s Health Initiative (WHI) randomized control
study consisted of a series of randomized clinical trials designed
to compare estrogen alone7 or combined estrogen–progesterone...