Hormone Therapy and Dementia Risk: A Critical Window?

Several observational studies have demonstrated a reduced risk for dementia in women who use hormone therapy (HT). However, well-designed interventional trials of estrogen–progesterone combinations have revealed an increased risk for dementia, cancer, and vascular events associated with HT use. This prospective cohort study was designed to further investigate the critical window theory that estrogen is beneficial only immediately before and immediately after menopause and may have deleterious effects in later life. More than 5000 women without dementia at baseline had been screened between ages 40 and 55 and reported whether they used HT (i.e., midlife use). Thirty years later, the authors identified participants' HT use (i.e., later-life use) from pharmacy databases. Starting when the cohort reached a median age of 80, the authors identified dementia from ICD-9 coding of diagnoses by neurologists, neuropsychologists, and internists; dementia assessment lasted 7.5 years.

During dementia assessment, 27% of the cohort received a diagnosis of dementia. Women who reported taking HT at midlife but had no evidence of later-life HT use had a significantly decreased risk for dementia diagnosis (adjusted hazard ratio, 0.74). In contrast, those who did not report midlife HT use but had evidence of later-life use had a significant increase in risk (AHR, 1.48). Women who had used HT in both midlife and later life had similar risks to those of women who had no evidence of HT use.