Hormone therapy and AD risk

Does the timing of menopausal HT affect the risk of Alzheimer's disease (AD)? Several studies have suggested the timing of postmenopausal HT is critical, especially during the first 5 years after menopause when hormones appear to be somewhat neuroprotective. The Women's Health Initiative (WHI) study clearly showed that starting HT after age 65 had no effect on cognition and in fact may be harmful. Now a new study confirms that starting HT immediately after menopause may have neuroprotective benefits. In a follow-up from the Cache County study, 1768 women provided a detailed history on age at menopause and use of HT between 1995 and 2006. During this interval, 176 women developed AD. Women who used any type of HT within 5 years of menopause were at 30% less risk of AD (95% CI, 0.49-0.99), especially if they used it for 10 years or more. By contrast, woman who started HT 5 or more years after menopause did not have a decreased rate of AD. Confirming the WHI findings, rates of dementia were nearly doubled among those who began combination estrogen-progesterone compounds later in life. The authors conclude that the association of HT and the risk of AD may depend on the timing of use. HT appears to be beneficial during the critical window near menopause, but may be associated with an increased risk if initiated later in life. (Neurology 2012;79:1846-1852). An accompanying editorial suggests that AD and coronary heart disease share common risk factors. WHI data show that women assigned to HT close to menopause had a reduction in the risk of coronary heart disease, whereas women given HT later in life had increased risk. The same seems to be true for the risk of AD. Two soon-to-be published studies will provide evidence regarding hormone effects on cognition in younger postmenopausal women (Neurology 2012;79:1840-1841). The decision to initiate HT in postmenopausal women is generally based on severity of symptoms, risk of breast cancer, risk of venous thromboembolic disease, and other factors. Benefits on cognition and potential protection against AD may now need to be added to the equation.