Relationship between hypothalamic-pituitary-adrenal axis activity and menstrual irregularities in women with...

This study was conducted to assess hypothalamic-pituitary-adrenal axis activity, perceived stress, and metabolic markers across menstrual status categories in women with polycystic ovary syndrome (PCOS), and to test whether perceived stress is independently associated with menstrual irregularity.

In this retrospective cross-sectional study, 296 women with PCOS (2023-2024) were classified as having regular menses, oligomenorrhea, or amenorrhea. Hormonal, metabolic, and biochemical parameters were recorded, and perceived stress was measured using the 10-item Perceived Stress Scale (PSS-10). Correlations, multivariable logistic regression (amenorrhea vs. other categories), and receiver operating characteristic analyses were performed.

PSS score was correlated with homeostatic model assessment of insulin resistance (HOMA-IR) (r=0.619, p<0.001), as well as cortisol (r=0.81, p<0.001), adrenocorticotropic hormone (r=0.72, p<0.001), and high-sensitivity C-reactive protein (hs-CRP) (r=0.609, p<0.001) levels. As menstrual irregularity worsened, HOMA-IR, hs-CRP level, and PSS score increased. HOMA-IR independently predicted amenorrhea (odds ratio, 1.86; p=0.025; area under the curve [AUC], 0.554; cut-off, 4.02; sensitivity, 14%; specificity, 98%). However, after adjustment for age, body mass index, medications, luteinizing hormone/follicle-stimulating hormone level, and testosterone level, the PSS score was not independently associated with menstrual irregularity and showed low discrimination (AUC, 0.57). These findings suggest that the observed association between perceived stress and menstrual irregularity may operate indirectly via metabolic and inflammatory pathways.

In PCOS, menstrual irregularity aligns more closely with metabolic and inflammatory markers than with perceived stress itself; after adjustment, PSS-10 score is not an independent predictor.