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The typical “mature woman” is aged 40 years or older and has completed childbearing. During their late 40s, most women enter menopausal transition. Detailed in Chapter 21, this period of physiologic change due to ovarian senescence and estrogen decline is usually completed between ages 51 and 56. Menopause marks a defining point in this transition and is defined as the point in time of permanent menstruation cessation due to loss of ovarian function. Clinically, the menopause refers to a point in time that follows 1 year after cessation of menstruation.

With ovarian senescence, declining hormone estrogen levels have specific effects. Some lead to physical symptoms, such as vasomotor symptoms and vaginal dryness, whereas others are metabolic and structural changes. These include bone loss, skin thinning, fatty replacement of the breast, lipoprotein changes, and genitourinary atrophy. As a result, postmenopausal women have unique issues associated with aging and estrogen loss that may negatively affect their individual health.

For many years, menopause was seen as a “deficiency disease” of estrogen, progesterone, and testosterone. For this reason, hormone replacement therapy has been used in one form or another for more than 100 years. The history surrounding this treatment is discussed here, as are current recommendations for the treatment of menopausal symptoms.


Clinicians ideally provide evidence-based medicine, and seldom is a single study relied on solely to guide practice (Lobo, 2008). Thus, providers should understand the weaknesses and strengths of clinical trials to accurately counsel their patients. As one example, hormone treatment (HT) was widely prescribed to menopausal women, in good faith, based on initial observational studies. The general medical consensus was that HT, in addition to its prevention and treatment of osteoporosis, could protect against cardiovascular disease, stroke, and dementia. Subsequently, prospective, randomized controlled trials (RCTs) challenged the validity of these earlier observational studies. However, in this evaluation, clinicians must appreciate the type of population studied, the ages and risk factors of participating women, and the hormone regimens tested.

Early Estrogen Administration Trends

Estrogen treatment (ET) for menopausal symptom relief gained popularity in the 1960s and 1970s. Proponents promoted ET for its “preservation of youth” and prevention of chronic disease. By the mid-1970s, more than 30 million prescriptions were written for estrogen each year, and half of all menopausal women were using ET for a median of 5 years. Premarin (conjugated equine estrogen) was the fifth most prescribed drug in the marketplace.

In 1975, a study revealed a connection between endometrial cancer and ET. Investigators found a 4.5 times greater risk of this cancer in those using estrogen (Smith, 1975). As a result, the Food and Drug Administration (FDA) ordered labeling changes to state this higher risk. Progestins were then added in the 1980s to therapy regimens to significantly ...

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