Prior reproductive and non-reproductive depression, and depressive symptoms in menopausal transition
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Importance
The menopausal transition is associated with an increased risk of depression. Prior depression is a well-established risk factor, but studies do not distinguish between prior reproductive and non-reproductive depression.
Objective
To compare the associations of reproductive (i.e., premenstrual mood disorder and perinatal depression) and non-reproductive (i.e., not related to hormonal transitions) histories of depression with depressive symptoms during the menopausal transition.
Design
Cross-sectional analysis of questionnaire data from the Multidisciplinary Menopausal Outpatient Care Project (MOPP) collected between February 2023 and October 2025.
Setting
Menopause outpatient clinics Amsterdam, the Netherlands, including a specialized multidisciplinary menopause clinic.
Participants
In total 364 individuals were approached; 244 enrolled at baseline. After exclusions for age <40 (n=3), premature ovarian insufficiency (n=2), premenopausal status (n=1), age >58 with final menstruation >10 years earlier (n=12), bipolar disorder (n=5), and missing survey data (n=41), 180 participants were included.
Exposures
Premenstrual mood disorder measured with Premenstrual Symptom Screening Tool, perinatal depression with Edinburgh Postnatal Depression Scale Lifetime version, and reported prior non-reproductive depression in medical records.
Main outcome and measures
Depressive symptom severity measured with Inventory of Depressive Symptomatology-Self Rated. We used univariable and multivariable linear regressions; multivariable models accounted for overlap between exposures.
Results
Among 180 participants (median age 51; 61% perimenopausal and 39% postmenopausal), premenstrual mood disorder showed the strongest association with depressive symptom severity (B = 9.0, 95% CI 5.1–12.9, p < 0.001), followed by perinatal depression (B = 7.8, 95% CI 3.4–12.1, p < 0.001) and prior non-reproductive depression (B = 4.7, 95% CI 0.7–8.7, p = 0.021). In multivariable analysis, only premenstrual mood disorder (B = 7.2, 95% CI 2.4–12.1, p = 0.0037) and perinatal depression (B = 5.7, 95% CI 1.2–10.1, p = 0.013) remained associated with depressive symptom severity.
Conclusions and Relevance
Prior reproductive depression, but not prior non-reproductive depression, was associated with greater depressive symptom severity during the menopausal transition. A history of premenstrual mood disorder and/or perinatal depression may therefore help identify individuals at increased vulnerability to depressive symptoms during this period. Future studies should replicate these findings in population-based samples.
Key points
Question
Are histories of prior reproductive depression (i.e., premenstrual mood disorder or perinatal depression) and non-reproductive depression (i.e., not related to hormonal transitions) differentially associated with depressive symptoms during the menopausal transition?
Findings
In this cross-sectional study of 180 perimenopausal and postmenopausal patients attending menopause outpatient clinics, prior reproductive depression, but not prior non-reproductive depression, was associated with greater depressive symptom severity during the menopausal transition.
Meaning
A history of reproductive depression may help identify individuals at increased risk for depressive symptoms during the menopausal transition.
