Objective: The study aim was to determine the relation between menopausal hormone therapy and Alzheimer’s disease, dementia, and Parkinson’s disease in human subjects.

Background: We performed a time-response meta-analysis evaluating the influence of menopausal HT on Alzheimer’s disease, Parkinson’s disease and all-cause dementia development.

Method: A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between them in menopausal women were reported in 28 studies.

Results: Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer’s disease (OR 1.08, 95 %CI 1.03–1.14, I2 : 69 %). This relationship was more pronounced in patients receiving the combined estrogen progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer’s disease was also identified (Coef1 = 0.0477, p1 < 0.001; Coef2 = -0.0932, p2 < 0.001). Similarly, pooled analysis revealed a significant association between hormone therapy and all-cause dementia (OR 1.16, 95 % CI 1.02–1.31, I2 : 19 %). Interestingly, no comparable relationship was uncovered between
hormone therapy as a whole and Parkinson’s disease (OR 1.14, 95 % CI 0.95–1.38, I2 : 65 %); however, sub-group  analysis revealed a significant relationship between the disease and progestogen (OR 3.41, 95 % CI 1.23–9.46) or combined estrogen-progestogen formulation use (OR 1.49, 95 % CI 1.34–1.65). Indeed, this association was also
found to be driven by duration of exposure (Coef1 = 0.0626, p1 = 0.04).

Conclusion: This study reveals a signifificant direct relationship between the use of certain hormonal therapies and Alzheimer’s disease, all-cause dementia, and Parkinson’s disease in menopausal women. However, the association appears to shift in direct after five years in the context of Alzheimer’s disease, adding further weight to the critical window or timing hypothesis of neurodegeneration and neuroprotection.

References: [1] M.G. Erkkinen, M.O. Kim, M.D. Geschwind, Clinical neurology and epidemiology of the major neurodegenerative diseases, Cold Spring Harb. Perspect. Biol. 10 (4) (2018). [2] K. Andersen, L.J. Launer, M.E. Dewey, L. Letenneur, A. Ott, J.R. Copeland, et al., Gender differences in the incidence of AD and vascular dementia: the EURODEM studies. EURODEM Incidence Research Group, Neurology 53 (9) (1999) 1992–1997. [3] R.M. Kutlešić, J. Popović, M. Stefanović, P. Vukomanović, A. Andrić, J. Milošević, Menopausal hormone therapy: benefits and different forms, Med. Pregl. 69 (7-8) (2016) 247–254.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/postmenopausal-hormone-therapy-and-alzheimers-disease-dementia-and-parkinsons-disease-a-systematic-review-and-time-response-meta-analysis/