PMOS Linked to 4-Fold Atherosclerotic Heart Disease Risk in 2.5 Million US Women

Women with polyendocrine metabolic ovarian syndrome (PMOS) (the condition renamed from polycystic ovary syndrome (PCOS) earlier this year) carried more than 4 times the adjusted risk of atherosclerotic cardiovascular disease (ASCVD) as matched peers. Interestingly, traditional risk factors explain only about a third of the excess, according to a nationwide claims analysis of nearly 2.5 million women published in The Lancet Obstetrics, Gynaecology & Women's Health.¹ 

The findings put quantitative weight behind a designation the field has already adopted. The 2026 ACC/AHA prevention guideline lists the condition among the risk-enhancing factors that should push clinicians toward more aggressive lipid-lowering when calculated risk is ambiguous, as previously covered by the American Journal of Managed Care^® (AJMC^®).²

What the Optum Claims Analysis Measured

Researchers drew on Optum's de-identified Clinformatics Data Mart, covering commercial and Medicare Advantage claims from 2000 to 2022. They identified 413,450 women aged 18 to 50 years with PMOS, captured either by diagnostic codes for the condition or by codes for the combination of irregular menses and hirsutism, and matched them 1:5 by age and month of diagnosis to 2,067,250 women without it. Anyone with a prior ASCVD event was excluded, and both groups required at least 183 days of continuous enrollment before the index date. The mean follow-up was 3.7 years in the PMOS group and 3.5 years in the reference group.

Composite ASCVD incidence reached 4.52 per 1000 person-years in the PMOS group vs 0.78 in the reference group, an adjusted hazard ratio (aHR) of 4.40 (95% CI, 4.23-4.58). Individual components moved in the same direction: coronary artery disease (aHR, 4.41), cerebrovascular disease (aHR, 4.33), and peripheral artery disease (aHR, 4.98). Acute events showed somewhat lower but still substantial elevations, including myocardial infarction (aHR, 3.45) and ischemic stroke (aHR, 3.50). By 10 years, adjusted absolute risk of composite ASCVD reached 12.16% in the PMOS group against 4.21% among matched controls.

Why Traditional Risk Factors Don't Explain the Gap

The PMOS cohort entered the study measurably sicker. At baseline, 20.7% had obesity compared with 8.2% of the reference group; 7.3% had type 2 diabetes vs 2.3%; and 12.5% had hypertension vs 6.6%. Metformin use diverged most sharply, at 17.9% vs 1.1%.

Mediation analyses tested whether that burden accounted for the outcome gap. Individually, incident hypertension, type 2 diabetes, hyperlipidemia, and obesity each mediated between 10.0% and 15.6% of the association; combined, they mediated 36.3% (95% CI, 34.8%-37.9%), leaving roughly two-thirds unexplained. The authors flagged these results as exploratory, noting that causal mediation analysis rests on strong assumptions about unmeasured confounding.

Sensitivity analyses were held with age-adjusted models producing an aHR of 4.67. Removing combined hormonal contraception and metformin from the model gave 4.52, and excluding participants with missing race or education data gave 4.48. A calculated e-value of 8.27 indicates an unmeasured confounder would need a hazard ratio above 8 with both exposure and outcome to explain away the association.

Senior author Anuja Dokras, MD, MHCI, PhD, who directs Penn's PMOS Center, said the results make it "imperative for clinicians to closely track and evaluate cardiovascular health" in these patients.³

What the PCOS-to-PMOS Rename Means for Case Finding

Identification remains the bottleneck. The authors noted that prevalence predicted by diagnostic coding has historically run below expected rates, which is why they broadened their case definition and observed that any residual misclassification would bias results toward the null, making their estimates conservative.¹ World Health Organization figures indicate that around 70% of affected women do not know they have the condition.³

The renaming compounds the near-term coding question. As AJMC® reported in May, the global consortium behind the change laid out a 3-year transition that includes updates to electronic health records and International Classification of Diseases systems, with the international guideline expected to adopt the terminology in 2028.⁴ Claims-based risk stratification will need to span both labels through that window.

What This Means for Payers and Prevention

For plans, the combination is unusual, as it is a common condition with a young and largely commercially insured population and events that begin accruing well before conventional screening thresholds. Existing international guidance already recommends cardiovascular risk assessment at the diagnosis visit, but the authors point to patient surveys reporting delayed diagnosis and dissatisfaction with counseling on long-term comorbidities.

The authors called for longitudinal work following this premenopausal cohort through menopause and for studies of whether PMOS phenotypes and interventions, including anti-androgens, metformin, glucagon-like peptide-1 receptor agonists, and combined hormonal contraception, modify the association. 

References

1. Alur-Gupta S, DiTosto JD, Lewey J, et al. Atherosclerotic cardiovascular disease risk in polyendocrine metabolic ovarian syndrome: a nationwide, US, claims-based, retrospective, longitudinal, cohort study. Lancet Obstet Gynaecol Womens Health. Published online July 20, 2026. doi:10.1016/S3050-5038(26)00090-7
2. Michos ED. Risk enhancers, calcium scoring, and the full picture of cardiovascular prevention. AJMC. April 28, 2026. Accessed July 20, 2026. https://www.ajmc.com/view/risk-enhancers-calcium-scoring-and-the-full-picture-of-cardiovascular-prevention
3. PMOS, formerly PCOS, raises risk of atherosclerotic cardiovascular disease, heart attacks, strokes. News release. Perelman School of Medicine at the University of Pennsylvania; July 20, 2026. Accessed July 20, 2026. https://www.pennmedicine.org/news
4. Hohmann E. PCOS renamed PMOS in landmark shift reflecting metabolic and endocrine features. AJMC. May 13, 2026. Accessed July 20, 2026. https://www.ajmc.com/view/pcos-renamed-pmos-in-landmark-shift-reflecting-metabolic-and-endocrine-features