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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


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.


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).


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


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...

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