TOPLINE
Menopausal hormone therapy (MHT) initiation in perimenopausal and recently postmenopausal women with vasomotor symptoms was associated with a reduction in the risk for cardiovascular disease (CVD).
METHODOLOGY
- Researchers emulated a sequence of target trials — using data from a longitudinal study of the menopause transition, with data collected from 1996 to 2017 — to assess the effect of initiating MHT during perimenopause or early postmenopause on the risk for CVD in women with any vasomotor symptoms.
- A total of 2737 women aged 42 years or older who reported hot flashes and/or night sweats over the past 2 weeks, were CVD-free, and had no prior MHT use were included.
- Among them, 755 women (mean age, 53.7 years; 23.9% Black individuals; 59.9% White individuals) initiated MHT — systemic oral or transdermal estrogen with or without progestogens, including oral contraceptives — with a mean follow-up duration of 9.6 years. Noninitiators had a mean follow-up duration of 11.8 years.
- The primary outcome was a composite of fatal and nonfatal CVD events (myocardial infarction, stroke, congestive heart failure, and revascularization), with 224 events reported during follow-up.
- The study assessed whether the timing of MHT initiation relative to menopause and race and ethnicity modified the effect of MHT on the risk for CVD.
TAKEAWAY
- MHT initiation was associated with a reduced risk for composite CVD events compared with noninitiation (adjusted hazard ratio [aHR], 0.78; 95% CI, 0.62-0.98).
- Women who initiated MHT within 10 years after menopause onset had a lower risk for CVD than those who did not initiate MHT (aHR, 0.73; 95% CI, 0.58-0.93).
- MHT initiation was associated with a lower risk for CVD among Black women (aHR, 0.51; 95% CI, 0.33-0.81), whereas no clear effects were observed among White women or women of other races.
IN PRACTICE
"Although we observed lower CVD risk among women initiating MHT less than 10 years from the FMP [final menstrual period], our findings do not support the use of MHT for CVD prevention," the authors wrote. "[O]ur study is uniquely positioned to provide additional evidence for perimenopausal and recently postmenopausal women with VMS [vasomotor symptoms] who are considering MHT and concerned about CVD risk."
"[The study] establishes a timely foundation and provides strong observational evidence that the effect on CVD risk of hormone therapy initiation among perimenopausal and recently postmenopausal women with VMS varies by time since menopause and race and ethnicity. However, [the study] also highlights that the definitive trials needed to guide clinical decision-making and advance the health of millions of women have yet to be conducted," experts wrote in an invited commentary.
SOURCE
The study was led by Ziyuan Wang, PhD, of the University of Pittsburgh School of Public Health in Pittsburgh. It was published online on September 8, 2026, in JAMA Internal Medicine.
LIMITATIONS
Residual confounding may still affect the findings, even after accounting for many factors. All CVD events were not adjudicated. Those who used the treatment only briefly might be misclassified as noninitiators, and losing early cases among initiators could affect the results.
DISCLOSURES
The SWAN study was supported by grants from the National Institutes of Health (NIH), Department of Health and Human Services through the National Institute on Aging (NIA), National Institute of Nursing Research, the NIH Office of Research on Women's Health, and the SWAN Repository. Some authors reported receiving grants from the NIA, NIH, or University of Pittsburgh during the conduct of the study. Several authors reported receiving grants or personal, advisory, or consulting fees from various organizations or companies unrelated to this work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.