Abstract Body: Introduction: Frequent and/or persistent vasomotor symptoms (VMS) are associated with cardiovascular disease (CVD) risk. Although menopausal hormone therapy (HT) is the standard treatment for VMS, no clinical trial data exist to assess its effects on CVD risk in women with VMS. This study uses observational data to emulate a target trial of HT initiation on CVD risks among women with VMS and to understand how the timing of HT initiation relative to menopause modifies this risk.

Methods: SWAN is an ongoing longitudinal study of the menopause transition into early old age. Between SWAN’s visit 0 (1997) and visit 16 (2017), HT use (systemic estrogen with/without progestogens, including oral contraceptives for non-contraceptive use) since prior visits was self-reported and verified from pill bottles and coded according to the Iowa Drug Information Service system. VMS, assessed at each visit, was defined as the self-reported presence of hot flashes or night sweats over the past 2 weeks. CVD events (myocardial infarction, stroke, heart failure, and revascularization) were self-reported; a subset of CVD events was adjudicated via medical records. We emulated a series of sequential trials among women with VMS and no history of HT, with eligibility assessed at SWAN visits 0-15. Adjusting for baseline confounders (listed in Figure) in pooled logistic regression models, we estimated the effect of initiating vs. not initiating HT on CVD events among women with VMS.

Results: Among 2737 women who reported VMS (46% White, 34% Black, 8% Japanese, 7% Chinese, 4% Hispanic), 1181 initiated HT at some point during the SWAN follow-up at a mean±SD age of 55±5 years. Over 20 years of follow-up, 152 CVD events occurred (44% adjudicated). The adjusted hazard ratio of CVD for HT initiation vs. non-initiation was 0.73 (95% CI: 0.52-1.02), Figure. Stratified by HT initiation relative to the time since onset of menopause, the adjusted hazard ratio was 0.60 (0.36-0.99) and 1.03 (0.33, 3.20) among women initiating HT ≤ 10 years versus > 10 years of the onset of menopause, respectively (interaction p value=0.48).

Conclusions: HT initiation contributed an estimated 27% reduction in CVD risk, but wide confidence intervals included the null. The magnitude of the estimated protective effect was greater among women who initiated HT ≤10 years postmenopause. Given potential residual confounding and confidence intervals that included 1, our results should be interpreted cautiously.