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.

Importance  It is clear that mental disorders in treatment settings are associated with a higher incidence of chronic physical conditions, but whether this is true of mental disorders in the community, and how generalized (across a range of physical health outcomes) these associations are, is less clear. This information has important implications for mental health care and the primary prevention of chronic physical disease.

Objective  To investigate associations of 16 temporally prior DSM-IV mental disorders with the subsequent onset or diagnosis of 10 chronic physical conditions.

Design, Setting, and Participants  Eighteen face-to-face, cross-sectional household surveys of community-dwelling adults were conducted in 17 countries (47 609 individuals; 2 032 942 person-years) from January 1, 2001, to December 31, 2011. The Composite International Diagnostic Interview was used to retrospectively assess the lifetime prevalence and age at onset of DSM-IV–identified mental disorders. Data analysis was performed from January 3, 2012, to September 30, 2015.

Main Outcomes and Measures  Lifetime history of physical conditions was ascertained via self-report of physician’s diagnosis and year of onset or diagnosis. Survival analyses estimated the associations of temporally prior first onset of mental disorders with subsequent onset or diagnosis of physical conditions.

Results  Most associations between 16 mental disorders and subsequent onset or diagnosis of 10 physical conditions were statistically significant, with odds ratios (ORs) (95% CIs) ranging from 1.2 (1.0-1.5) to 3.6 (2.0-6.6). The associations were attenuated after adjustment for mental disorder comorbidity, but mood, anxiety, substance use, and impulse control disorders remained significantly associated with onset of between 7 and all 10 of the physical conditions (ORs [95% CIs] from 1.2 [1.1-1.3] to 2.0 [1.4-2.8]). An increasing number of mental disorders experienced over the life course was significantly associated with increasing odds of onset or diagnosis of all 10 types of physical conditions, with ORs (95% CIs) for 1 mental disorder ranging from 1.3 (1.1-1.6) to 1.8 (1.4-2.2) and ORs (95% CIs) for 5 or more mental disorders ranging from 1.9 (1.4-2.7) to 4.0 (2.5-6.5). In population-attributable risk estimates, specific mental disorders were associated with 1.5% to 13.3% of physical condition onsets.

Conclusions and Relevance  These findings suggest that mental disorders of all kinds are associated with an increased risk of onset of a wide range of chronic physical conditions. Current efforts to improve the physical health of individuals with mental disorders may be too narrowly focused on the small group with the most severe mental disorders. Interventions aimed at the primary prevention of chronic physical diseases should optimally be integrated into treatment of all mental disorders in primary and secondary care from early in the disorder course.