Supplementary Material for: Physical Activity, Hormone Therapy Use, and Stroke Risk among Women in the California Teachers Study Cohort

Background: Postmenopausal hormone therapy (HT) increases the risk of stroke. Here we evaluate whether leisure time physical activity (LTPA) can change stroke risk in women using HT, leveraging data from the California Teachers Study. Methods: Female California educators without a prior history of stroke (n = 118,294) were followed from 1995 through 2015 for stroke end points. Based on statewide hospitalization data, 4,437 women had ischemic (n = 3,162; International Classification of Diseases [ICD]-9 433, 434, 436) or hemorrhagic (n = 1,275; ICD-9 430–432, excluding 432.1) stroke. LTPA and HT use were evaluated at 2 time points (baseline [1995–1996] and 10-year follow-up [2005–2006]). LTPA was assessed using American Heart Association (AHA) recommendations (>150 min/week moderate or >75 min/week strenuous physical activity). Using multivariable Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% CIs for the associations between HT use and concurrent LTPA with incident stroke. Results: Compared to women who never used HT, stroke risk was highest among women who were current HT users and did not meet AHA recommendations for LTPA at the time of their HT use: HR_baseline 1.28 (95% CI 1.13–1.44); HR_{10-year follow-up} 1.17 (95% CI 0.91–1.50). Based on the baseline questionnaire, current HT users who met AHA recommendations for LTPA in 1995–1996 still had elevated stroke risk in the 20-year follow-up (HR 1.22, 95% CI 1.08–1.37). However, among current HT users who met AHA recommendations for LTPA at the 2005–2006 follow-up questionnaire, stroke risk was not elevated (HR 1.01, 95% CI 0.80–1.29). Evaluation of the 2 time points in concert further demonstrated that meeting AHA recommendations for LTPA at the most recent follow-up time point was required to reduce HT-related stroke risk. Conclusion: Concurrent physical activity may attenuate the short-term increase in risk of stroke risk associated with HT use.