Is genetic predisposition to immune cell changes linked to premenstrual disorders and their severity?

Abstract Background Premenstrual disorders (PMD), including premenstrual syndrome (PMS) and the more severe premenstrual dysphoric disorder (PMDD), are burdensome conditions with unclear mechanisms. While inflammation is implicated, biomarker research is challenged by inconsistent findings and cyclical fluctuations. This study utilized polygenic risk scores (PRS) to investigate the association between lifelong genetic predisposition to altered immune-related cell counts and PMD risk and symptom severity. Methods This cross-sectional study included 1,730 Chinese college students from the Care of Premenstrual Emotion cohort. PRS were calculated for seven immune biomarkers: white blood cell (WBC), basophil, eosinophil, lymphocyte, monocyte, neutrophil, and C-reactive protein. Probable PMD cases and symptom severity (total, physical, affective) were assessed using a modified Calendar of Premenstrual Experiences. Generalized estimating equations estimated risk ratios (RR) and β-coefficients, adjusting for confounders. Results Overall, 424 (24.5%) participants met probable PMD criteria, including 379 (21.9%) with PMS and 45 (2.6%) with PMDD. The PRS for WBC showed a suggestive, non-significant association with diagnosis (RR, 1.08; 95% CI, 1.00–1.18; P = 0.062). No other immune PRS showed significant associations. A higher PRS for WBC was associated with physical symptom severity (β = 0.05; 95% CI, 0.00–0.10; P = 0.047). This association was stronger in women with symptom onset at menarche (β = 0.47; 95% CI, 0.15–0.78; P = 0.008). The highest quintile of PRS for WBC exhibited greater severity across all domains versus the lowest, suggesting a possible graded pattern. Item-level analyses suggested signals for limb swelling, increased appetite, and food cravings. Conclusions The PRS for WBC may be associated with premenstrual symptom severity, specifically physical domains. These findings suggest that inflammatory liability may contribute to the physical symptom burden of PMD, but replication in prospectively phenotyped cohorts with detailed gynecologic and medical comorbidity data is needed. Trial registration Not applicable.

Reproduced under CC-BY.