SUN-157 - Are Ssris Associated with Higher Cardiovascular and Metabolic Risk in PCOS? Determining the Five-Year Outcomes in A National US EHR Cohort

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women and is associated with increased risk of cardiovascular and metabolic disease. Psychiatric comorbidity is also common in PCOS, yet the cardiovascular and metabolic safety of SSRIs, endorsed by guidelines as first-line therapy for depression and anxiety, remains poorly characterized. To address this evidence gap, we determined whether SSRI initiation after a PCOS diagnosis is associated with increased 5-year cardiovascular and metabolic risk factors.
We conducted a retrospective cohort study using the TriNetx US Collaborative Network, a clinical informatics platform, to compare outcomes for patients with PCOS based on patient electronic health records from 70+ US health systems. Inclusion criteria included women aged 18–45 diagnosed with PCOS, identified by ICD-10 codes, who initiated SSRIs and had at least 3 recorded SSRI prescriptions within 1 year of diagnosis (n=8,303). We compared them to PCOS patients with no recorded SSRI exposure (n=226,157). The index date was the first SSRI prescription after PCOS diagnosis, matched to an index date in control subjects. Patients with significant baseline comorbidities were excluded. Propensity score matching on age, race, mental disorders, substance use, prediabetes, spironolactone use, and contraceptive use produced matched cohorts (n=8,061 per cohort) with no statistically significant baseline differences. Cardiovascular and metabolic outcomes were assessed 5 years post-index. Compared with matched PCOS patients without SSRIs, SSRI-exposed patients had higher 5-year risk of (1) type 2 diabetes (RR=1.536; 95% CI: 1.315 and 1.794, p < .001), (2) metabolic syndrome and insulin resistance (RR= 1.495; 95% CI: 1.344 and 1.662, p < .001), (3) overweight or obesity (RR= 1.461; 95% CI: 1.361 and 1.569, p < .001), (4) hypertriglyceridemia (triglycerides ≥150 mg/dL) (RR= 1.853; 95% CI: 1.674 and 2.051, p < .001), and (5) hypertension (RR= 1.284; 95% CI: 1.205 and 1.369, p < .001).
These findings suggest SSRI use in women with PCOS was associated with increased 5-year risks for adverse cardiovascular and metabolic outcomes, underscoring the need for risk–benefit discussions when selecting psychiatric medications and metabolic monitoring in this high-risk population.

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