Postmenopausal hormone therapy not significantly linked to dementia risk

Public examination of a doctoral dissertation in the field of Neurology

Doctoral candidate: MD, MPH Bushra Imtiaz

Date and venue: 20.1.2017 at 12 noon, Canthia, CA100, Kuopio Campus

According to the doctoral thesis of Bushra Imtiaz, MD, MPH, postmenopausal hormone therapy use is not significantly associated with dementia and Alzheimer’s disease (AD). However, long term use, that is, hormone therapy use exceeding ten years, was associated with a decreased risk of AD. This may be due to differences between long-term and short-term users, or timing of hormone therapy.

Imtiaz’s thesis explored the association between hormone therapy, Alzheimer’s disease, dementia and cognition in two nation-wide case-control studies and two longitudinal cohort studies. Findings of previous studies on the use of hormone therapy after the onset of menopause have been inconsistent.

Alzheimer’s disease is more common in women – menopause may play a role

AD is the most common cause of dementia accounting for 60-80% of cases. Worldwide 2/3rd of AD cases are females. Women undergo menopause at an average age of 51 years, which due to higher life expectancy nowadays is considered a midlife event. Consequently, women spend one third of their life span in post menopause. Postmenopausal depletion of estrogen and progesterone may be one explanation for the higher dementia risk among women when compared to men.   

Estrogen receptors are widely distributed throughout human body including brain especially in those areas which are primarily affected in AD, i.e., hippocampus. According to in vitro and animal studies estrogen is a neuroprotective hormone. It may exert neuroprotection through, for example, enhancement of mitochondrial function, improvement in glucose transport and blood flow in brain. Thus, depletion of sex steroid hormones at menopause is a biologically plausible explanation for higher risk of AD among women.

The timing of hormone replacement therapy may matter

Association between hormone therapy and AD is a complex scenario as it is affected by a number of genetic (APOE ε4 status) and lifestyle-related factors such as education, physical activity, smoking, socioeconomic status and social activity. Other important factors prevailing in this association are type and stage of menopause, time since menopause with respect to start of hormone therapy along with type, duration, and formulation of hormone therapy. Studies in Imtiaz’s thesis explored the association of postmenopausal gynecological surgeries i.e. removal of ovaries, uterus or both with AD and use of hormone therapy with AD and cognition in two nationwide case-control studies and two longitudinal cohort studies.

Findings from the thesis conclude that postmenopausal removal of ovaries, uterus or both is not a significant predictor of AD irrespective of indication of surgery or hormone therapy use. Long term use of hormone therapy was associated with better performance in certain cognitive domains – global cognition and episodic memory – and lower risk of AD. However, short-term use among women under 65 years of age was related to higher risk of AD. Although the results were adjusted for several lifestyle factors and socioeconomic position, it is possible that these results are explained by the differences between long- and short-term users. Alternative possibility is that hormone therapy has cognitive benefits if started around menopause when neurons are healthy and responsive to estrogen-based hormone therapy.

The doctoral dissertation of MD, MPH Bushra Imtiaz, entitled Hormone therapy and the risk of dementia, cognitive decline, and Alzheimer’s disease will be examined at the Faculty of Health Sciences. The Opponent in the public examination be Docent Kati Juva of HUS – The Hospital District of Helsinki and Uusimaa, and the Custos will be Professor Hilkka Soininen of the University of Eastern Finland.

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