Do genetics and stress factors affect how severe premenstrual symptoms are?

Background: Premenstrual disorders (PMDs) affect approximately one in three women of reproductive age and have a substantial impact on daily functioning and mental health. Given the challenges observed in diagnosis and clinical management, understanding whether genetic predisposition and readily assessable factors jointly mark greater symptom burden may help inform future risk-stratified monitoring and assessment. Methods: After excluding 424 participants with missing data, we conducted a cross-sectional study of 1528 female college students from the Care of Premenstrual Emotion (COPE) cohort in China. Premenstrual symptoms and probable PMD cases were assessed with the Calendar of Premenstrual Experiences. Four psychosocial and behavioural factors, including alcohol consumption, psychological resilience, adverse childhood experiences (ACEs), and body mass index (BMI), were recorded through electronic questionnaires. The polygenic risk score (PRS) of depression was derived from trans-ancestry genome-wide association study (GWAS) summary statistics. The associations and interactions of the PRS for depression and psychosocial and behavioural factors with premenstrual symptoms and probable PMD cases were examined. Results: The average age of the participants was 20.1 ± 1.59 years. Positive associations were observed between the depression PRS, alcohol consumption, low psychological resilience, ACEs, and premenstrual symptoms; additionally, positive associations between low psychological resilience, ACEs, and probable PMDs were observed. The psychosocial and behavioural factor score was associated with more severe premenstrual symptoms (β = 0.49, 95% CI: 0.35-0.62, P < 0.001) and higher odds of probable PMDs (OR = 1.97, 95% CI: 1.42-2.73, P < 0.001). Specifically, compared with participants with low depression PRS and no adverse psychosocial-behavioural factors, participants with high depression PRS and alcohol consumption (β = 0.32, 95% CI: 0.14-0.51, P = 0.001), low psychological resilience (β = 0.54, 95% CI: 0.33-0.75, P < 0.001) or ACEs (β = 0.26, 95% CI: 0.08-0.43, P = 0.003) exhibited more severe premenstrual symptoms; moreover, participants with high depression PRS and ≥ 2 psychosocial-behavioural factor scores demonstrated the greatest burden of premenstrual symptoms (β = 0.59, 95% CI: 0.37-0.81, P < 0.001) and higher odds of probable PMDs (OR = 1.79, 95% CI: 1.05-3.11, P = 0.035). Conclusions: If confirmed in prospective studies, a combined profile of genetic predisposition and psychosocial and behavioural factors may help identify young women who warrant closer evaluation for PMDs, and may inform future prevention-oriented studies focused on actionable exposures.

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