Using postmenopausal estrogen-based hormone therapy for more than 10 years is associated with a decreased risk of Alzheimer’s disease, a large Finnish study has found.
The study, by the University of Eastern Finland, explored the association between postmenopausal hormone replacement therapy, Alzheimer’s disease, dementia and cognition in 2 nationwide case-control studies and 2 longitudinal cohort studies. The largest study included about 230,000 Finnish women and the follow-up time in different studies was up to 20 years.
“The protective effect of hormone therapy may depend on its timing: it may have cognitive benefits if initiated at the time of menopause when neurons are still healthy and responsive,” said Bushra Imtiaz, MD, MPH, who presented the results in her doctoral thesis.
Alzheimer’s disease is the most common cause of dementia, and 2 out of 3 Alzheimer’s cases are women. One possible explanation for women’s higher dementia risk is the postmenopausal depletion of sex steroid hormones estrogen and progesterone. Estrogen receptors are present throughout the body including brain areas primarily affected in Alzheimer’s disease. In in vitro and animal studies, estrogen has showed neuroprotective effects. However, studies on humans have yielded inconsistent results on the association between postmenopausal estrogen-based hormone replacement therapy and dementia risk.
In this study, long-term use of hormonal replacement therapy was associated with a better performance in certain cognitive domains – global cognition and episodic memory – and a lower risk of Alzheimer’s disease. Short-term use was not significantly linked to dementia risk, but in one cohort, dementia risk was higher among short-term users who had started hormone therapy in the late postmenopausal period. The results were adjusted for various lifestyle, socioeconomic and demographic variables.
“In the light of these findings, hormonal replacement therapy may have a beneficial effect on cognition if started early, around the time of menopause. The protective effect of hormonal therapy may depend on the health status of neurons at baseline and may be lost if therapy starts years after menopause,” added Dr Imtiaz.
The study also showed that the postmenopausal removal of ovaries, uterus or both did not have a significant link to the risk of Alzheimer’s disease, irrespective of the indication of surgery or hormone therapy use.
The research data was from the MEDALZ (Medication use and Alzheimer’s disease), OSTPRE (Kuopio Osteoporosis Risk Factor and Prevention Study) and CAIDE (Cardiovascular Risk Factors, Aging and Dementia) studies. The newest results were published in Neurology and Maturitas and the earlier results in the Journal of Alzheimer’s disease.
Dr Imtiaz’s doctoral thesis Hormone therapy and the risk of dementia, cognitive decline and Alzheimer's disease can be downloaded here.