Chronic inflammatory activity in women with normogonadotropic anovulation complicated by subclinical thyroid dysfunction: a prospective cohort study

Purpose To investigate the impact of subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) on systemic inflammatory activity in women with normogonadotropic anovulation, comparing polycystic ovary syndrome (PCOS) and hypothalamic-pituitary-ovarian dysfunction (HPOD), and to examine the correlations of inflammatory parameters with thyroid, metabolic, and ovarian indices. Methods Concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6, interleukin-1β, and interleukin-10 were prospectively measured in anovulatory women and compared between those with PCOS and HPOD, considering the influence of SCH and TAI. Multiple regression analysis was performed to evaluate the relationships among thyroid dysfunction, inflammatory parameters, and indices of both metabolic and ovarian function. Results Both SCH and TAI independently increased TNF-α concentrations across the entire cohort (p=0.005 and p=0.018) and within the PCOS arm (p=0.018 and p=0.039). TAI significantly elevated the IL-1β/IL-10 ratio in the entire cohort (p=0.009) and in PCOS arm (p=0.005), with significant interaction effects between SCH and TAI in both groups (p=0.026 and p=0.017). No significant associations were found in the HPOD arm. In the overall cohort, CRP concentrations, which positively correlated with BMI, insulin resistance indicators, and dyslipidemia, and negatively with estradiol, were significantly higher in SCH (p-values 0.001). In PCOS, interleukin-1β and TNF-α levels, positively correlated with some insulin resistance indicators and TNF-α with AMH, were also significantly elevated in both SCH and TAI. Conclusions SCH and TAI independently and synergistically promoted chronic inflammation in normogonadotropic anovulation, particularly in PCOS, through elevated TNF-α and disrupted interleukin-1β/IL-10 balance, with significant implications for metabolic health and ovarian function.