Levothyroxine (LT4) monotherapy is standard treatment for hypothyroidism, yet fluctuations in circulating thyroid hormone levels may raise concerns about cardiovascular risk. This longitudinal analysis from the Study of Women's Health Across the Nation (SWAN) evaluated whether LT4 therapy was associated with incident cardiovascular disease (CVD) events in midlife women. The analysis was published in the Thyroid.

SWAN is a multisite cohort study including a diverse population of women from seven U.S. geographic regions. Women were screened for thyroid disease history and LT4 use. Participants completed up to 17 follow-up visits, during which fatal and nonfatal CVD events were adjudicated. The composite CVD outcome included myocardial infarction, stroke, heart failure, percutaneous coronary intervention, and coronary artery bypass graft surgery. A multivariable Cox proportional hazards model with time-varying exposure assessed the association between LT4 use and first CVD event. Sensitivity analysis stratified LT4 users by baseline thyrotropin (TSH) level.

Among 2,647 women, 421 (15.9%) received LT4 during follow-up. CVD events occurred in 33 (7.8%) LT4-treated women and 191 (8.6%) women without thyroid disease (p=0.616). In adjusted analysis, LT4 treatment was not significantly associated with CVD risk (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.55-1.31; p =  0.463). No significant association was observed after stratification by baseline TSH.

LT4 therapy was not associated with increased CVD risk in this cohort. Findings were consistent across TSH strata during long-term follow-up.