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 This cross-sectional study included 1,300 women with confirmed PCOS in the source dataset. Thyroid autoimmunity was defined a priori 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 analyses 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 analyses, including restriction to euthyroid women and trimming of extreme values. In exploratory analyses, 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.

The authors have declared no competing interest.

This research received no external funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Bioethics Committee at Wroclaw Medical University (Wrocław, Poland) granted ethical approval for this study (approval No. KB-254/2021, issued on 31 March 2021). The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The analysis used anonymized clinical data collected as part of routine care, in compliance with institutional data protection regulations.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes