Age at menopause and duration of reproductive period in association with dementia and cognitive function: A systematic review and meta-analysis

Marios K. Georgakis, Eleni I. Kalogirou, Andreas Antonios Diamantaras, Stella S. Daskalopoulou, Cynthia A. Munro, Constantine G. Lyketsos, Alkistis Skalkidou, Eleni Th Petridou

Research output: Contribution to journalArticlepeer-review


Introduction The preponderance of dementia among postmenopausal women compared with same-age men and the female sex hormones neuroprotective properties support a tentative role of their deficiency in the dementia pathogenesis. Methods Pairs of independent reviewers screened 12,323 publications derived from a search strategy for MEDLINE to identify articles investigating the association of age at menopause/reproductive period with (i) dementia and (ii) cognitive function; a snowball of eligible articles and reviews was conducted and authors were contacted for additional information. Random-effect models were used for the meta-analysis. Results Age at menopause (13 studies; 19,449 participants) and reproductive period (4 studies; 9916 participants) in the highest categories were not associated with odds of dementia (effect size [ES]: 0.97 [0.78–1.21]) and Alzheimer's disease (ES: 1.06 [0.71–1.58]). Significant heterogeneity was however noted in both analyses (I2: 63.3%, p = 0.003 and I2: 72.6%, p = 0.01, respectively). Subgroup analyses by outcome assessment, study design, level of adjustment and study quality did not materially change the findings. In 9/13 studies assessing cognitive function, advanced age at menopause/longer reproductive period was significantly associated with better cognitive performance/lower decline. Due to statistical differences, no meta-analysis was possible for cognitive function. Conclusions Existing evidence does not support an association between indices of prolonged exposure to female hormones and lower dementia risk. There are indications, however, for better cognitive performance and delayed cognitive decline, supporting a link between female hormone deficiency and cognitive aging. Current literature limitations, indicated by the heterogeneous study-set, point towards research priorities in this clinically relevant area.

Original languageEnglish (US)
Pages (from-to)224-243
Number of pages20
StatePublished - Nov 1 2016


  • Cognition
  • Cognitive impairment
  • Dementia
  • Female hormones
  • Menopause
  • Postmenopausal women

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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