Approximately 11,000 women without a uterus participated in a separate WHI study and were randomized either to estrogen alone or placebo. After an average follow-up of 7 years, there was no increased risk of heart disease or breast cancer in estrogen users. Outcomes were similar to those seen in the estrogen plus progestin arm of WHI with respect to venous thromboembolism, stroke, and osteoporotic fractures; there was no effect on colorectal cancer (52) (see Table 34.5 for a summary of WHI findings).
Studies confirmed that the increased risk of CHD in WHI occurs principally in older women and those who are a number of years beyond menopause (Table 34.6). In a secondary analysis of data from the combined WHI trials, no increased risk of CHD was seen in women between the ages 50 to 59 or in those within 10 years of menopause (53). Although stroke was increased with hormone therapy, regardless of age or years since menopause, the absolute excess risk of stroke in the younger women was minimal. These data do not support a
Table 34.5 Summary of Women’s Health Initiative Study Results
Risks per 10,000 Woman-Years Attributable to Estrogen Plus Progestin a
Risks per 10,000 Woman-Years Attributable to Estrogen Alone (Hysterectomized Women)b
WHIMS, Women’s Health Initiative Memory Study. a From Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–333; and Shumaker S, Legault C, Rapp S, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. JAMA 2003;289:2651–2662. bFrom Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. JAMA 2004;291:1701–1712.
Table 34.6 Absolute Excess Risk of Coronary Heart Disease and Mortality
Absolute excess risk of coronary heart disease and mortality (cases per 10,000 woman-years) by age and years since menopause in the combined trials (estrogen + progestin and estrogen alone) of the WHI. (Rossouw J, Prentice R, Manson J, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465–1477). aP = .03 compared with age 50–59 years or less than 10 years since menopause. bGlobal index is a composite of coronary heart disease, stroke, pulmonary embolism, breast cancer, colorectal cancer, endometrial cancer, hip fracture, and mortality. From Martin K, Manson J. Approach to the patient with menopausal symptoms. J Clin Endocrinol Metab 2008;93:4567–4575. Copyright 2008, The Endocrine Society.
role for hormone therapy in the prevention of heart disease, but they do provide reassurance regarding the safety of hormone therapy use for bothersome hot ﬂashes and night sweats in otherwise healthy women at the time of the menopausal transition.