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Thyroid autoimmunity does not delineate a cardiometabolic or androgenic phenotype in women with polycystic ovary syndrome: a pre-specified cross-sectional analysis

Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Thyroid autoimmunity (TAI) is frequently reported in women with polycystic ovary syndrome (PCOS), yet its clinical relevance for cardiometabolic and androgenic severity remains uncertain. We evaluated whether TAI identifies a metabolically or androgenically more severe PCOS phenotype using pre-specified exposure definitions and cardiometabolic endpoints. Methods: using three definitions: anti-thyroid peroxidase antibodies above the laboratory upper limit of normal (TAI_A, primary definition), anti-TPO positivity combined with thyroid-stimulating hormone >4.0 mIU/L (TAI_B), and high-titer anti-TPO >100 IU/mL (TAI_C). The primary endpoint was triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) >3.5. Secondary endpoints included non-HDL-C ≥130 mg/dL and 120-minute oral glucose tolerance test (OGTT) glucose ≥140 mg/dL. Associations were assessed using age-adjusted Firth logistic regression models in complete-case cohorts. Sensitivity analyzes included restriction to euthyroid participants, alternative TAI definitions, trimming of extreme values (1-99%), and bootstrap-based confidence intervals. Exploratory hormonal comparisons were adjusted using the Benjamini-Hochberg false discovery rate. Results: TAI_A was not significantly associated with the primary endpoint (TG/HDL >3.5) (OR 0.77, 95% CI 0.21-1.67). No significant associations were observed for secondary endpoints including non-HDL-C ≥130 mg/dL (OR 1.09, 95% CI 0.61-1.76) or impaired glucose tolerance on OGTT (OR 1.27, 95% CI 0.63-2.18). Results remained directionally consistent across alternative TAI definitions and sensitivity analyzes, including restriction to euthyroid women and trimming of extreme values. In exploratory analyzes, thyroid-stimulating hormone levels differed between TAI-positive and TAI-negative women, while no androgenic or cardiometabolic parameters remained significant after false discovery rate correction. Model diagnostics did not indicate major violations of model assumptions. Conclusion: In this large cross-sectional cohort of women with PCOS, thyroid autoimmunity was not associated with an adverse cardiometabolic or androgenic phenotype. Anti-TPO positivity alone therefore does not appear to identify a metabolically high-risk PCOS subgroup under the studied conditions. Prospective studies are needed to clarify the longitudinal implications of thyroid autoimmunity in PCOS.
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7160047319
FWCI:
Cites: 23
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