Menopause is the cessation of menses that signifies the depletion of ovarian follicle estradiol production. Even as life spans have lengths ened, the median age at the onset of menopause has remained constant at approximately 51 years; thus, the time women spend in a hormone-deficient state is increasing. So, too, are their risks for the detrimental metabolic and physiologic consequences of estrogen depletion.
Early research focused on the benefits of estrogen replacement therapy (ERT) for the relief of vasomotor complaints in perimenopausal women. Study has now shifted to the use of hormone replacement therapy (HRT) in preventing and treating diseases that typically occur decades after menopause. The proven efficacy of ERT to ameliorate symptoms and osteoporosis risks and its potential to reduce rates of cardiovascular disease and dementia have led to recommendations that all postmenopausal women consider using HRT.
The following case studies delineate issues in the contemporary pharmacologic management of menopause based on the results of recently reported clinical trials.
Case study #1
A 50-year-old with hot flushes documented to be perimenopausal by an elevated serum follicle stimulating hormone (FSH) value is fearful of initiating ERT because of a strong family history of breast cancer. What are alternative therapies to relieve her vasomotor symptoms? Why would a synthetic estrogen receptor modulator (SERM) not be an optimal choice?
Only 20% of postmenopausal women ever use HRT. The most frequently cited reason for this underutilization is fear of breast cancer. These fears are fostered by the failure of women, the media, and even physicians to understand risk reporting.
Epidemiologic studies garner relative risk as a sum
An ongoing CE program of
The University of Mississippi School of Pharmacy and DRUG TOPICS many measure of disease frequency. The risk of breast cancer from ERT is not 20%-30%, as commonly reported. This is merely the increased risk of breast cancer in women who receive ERT relative to those who do not:. A more meaningful statistic for clinical decision-making is the excess risk of breast cancer attributable to ERT use.
The association between HRT and breast cancer was the primary focus of a meta-analysis of 51 studies involving 160,000 postmenopausal women. This study revealed that the duration of ERT use is positively correlated with an increased relative risk-a linear increased risk of breast cancer of 2.3% each year,. A recently published report confirmed that these data could be integrated with incident rates from the National Cancer Institute to yield attributable risks for women considering ERT. In a population of 50-yearold women, 2.5 will develop breast cancer in 10 years. If the relative risk of breast cancer is increased 23% by ERT use over that period, then less than one additional woman would get a breast cancer she would otherwise avoid if she were not to take estrogen (i.e., a 2.5 incident rate multiplied by a 23% relative risk yields an attributable risk of 0.58). For a 50-year-old considering ERT, an attributable risk of approximately 0.6 means a less than a one-in-100 chance of incurring an estrogen-induced breast cancer over 10 years. Stated yet another way, approximately 97% of 50-year-old women using HRT for 10 years will not bet breast cancer. When understood more clearly, ERT associated cancer risks are less alarming.
The impact of HRT on other cancers is less clear. Clinical trials reveal an increased incidence of endometrial hyperplasia in women treated with unopposed ERT. When estrogen is used with a progestin, the increased risk of this precursor to endometrial cancer is alleviated (Table 1). Epidemiologic evidence of a protective effect of HRT on colorectal cancer is conflicting. The large-scale Women's Health Initiative (WHI), a randomized, controlled trial of the concurrent use of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) in 8,000 women, should clarify the nature and degree of HRT cancer risks when it is reported in 2002. …