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- Georgakis, Marios K., et al.
(author)
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Age at menopause and duration of reproductive period in association with dementia and cognitive function : A systematic review and meta-analysis
- 2016
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 73, s. 224-243
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Research review (peer-reviewed)abstract
- 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 (12: 63.3%, p = 0.003 and 12: 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.
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2. |
- Georgakis, Marios K, et al.
(author)
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Association of Age at Menopause and Duration of Reproductive Period With Depression After Menopause : A Systematic Review and Meta-analysis
- 2016
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:2, s. 139-149
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Research review (peer-reviewed)abstract
- Importance: Estrogens have neuroprotective and antidepressive effects; however, associations between indices of reduced endogenous estrogens and risk for postmenopausal depression have not been systematically explored.Objective: To investigate the association of age at menopause and the duration of the reproductive period with the risk for depression among postmenopausal women with naturally occurring menopause.Data Sources: A search strategy for use of MEDLINE was developed (through January 1, 2015) using the key terms menopause, climacteric, reproductive period, depression, and mood disorders. References of included studies and reviews were also screened; authors were contacted to maximize synthesized evidence.Study Selection: A total of 12 323 articles, without language restriction, were screened by pairs of reviewers to identify observational studies related to the study hypothesis; 14 studies were eligible for meta-analysis.Data Extraction and Synthesis: Pairs of reviewers independently extracted information on study design and type of analysis by participants' characteristics and methods of depression ascertainment. Study quality was assessed using the Newcastle-Ottawa Scale, and fixed- or random-effects models were implemented.Main Outcomes and Measures: Pooled-effect estimates for depression, defined by psychiatric evaluation or validated instruments, by age at menopause and duration of the reproductive period.Results: The 14 studies included in the meta-analysis represented 67 714 women. An inverse association (reported as odds ratio [OR]; 95% CI of 2-year increments) with depression in postmenopausal women was shown for increasing age at menopause (0.98; 0.96-0.99 [67 434 unique participants; 13 studies]) and duration of the reproductive period (0.98; 0.96-0.99 [54 715 unique participants; 5 studies]). Menopause at age 40 or more years compared with premature menopause was associated with a 50% decreased risk for depression (3033 unique participants; 4 studies). Pooling of studies examining severe depression showed a 5% decrease in risk of severe depression with increasing (2-year increment) age at menopause (52 736 unique participants; 3 studies); sensitivity analysis of studies controlling for past depression revealed similar results for age at menopause (0.98; 0.96-1.00 [48 894 unique participants; 3 studies). No heterogeneity or publication bias was evident in the main analyses.Conclusions and Relevance: Longer exposure to endogenous estrogens, expressed as older age at menopause and longer reproductive period, is associated with a lower risk of depression in later life. Identifying women at higher risk for depression due to early menopause who could benefit from psychiatric intervention or estrogen-based therapies could be useful in the clinical setting.
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