Study Finds Reduced Cardiovascular Risk With Hormone Therapy Initiation

Menopausal hormone therapy (MHT) initiated during perimenopause or early postmenopause was associated with a 22% reduction in cardiovascular disease (CVD) risk among women with vasomotor symptoms (VMS), according to a target trial emulation published in JAMA Internal Medicine.¹

Of 2737 women who reported any VMS—hot flashes, night sweats, or both—755 initiated MHT during the study period, with a mean age of 53.7 years (SD, 4.6) at initiation. Over the course of follow-up, 224 fatal and nonfatal CVD events occurred, including myocardial infarction, stroke, heart failure, and revascularization. The adjusted hazard ratio (aHR) for CVD events comparing MHT initiators with noninitiators was 0.78 (95% CI, 0.62-0.98).¹

Cardiovascular Benefit Depends on Timing of Initiation

The protective association was not uniform across the cohort. Women who started MHT within 10 years of menopause onset had an aHR of 0.73 (95% CI, 0.58-0.93), and those who initiated MHT more than 10 years after menopause had an aHR of 1.53 (95% CI, 0.66-3.52)—a statistically significant interaction (P = .02). A similar pattern held using a 6-year cutoff, with an aHR of 0.71 (95% CI, 0.55-0.91) for earlier initiators versus 1.16 (95% CI, 0.66-2.05) for later initiators (P = .01).¹

This pattern echoes the long-debated "timing hypothesis" in menopause research, which holds that the vascular effects of estrogen depend heavily on whether therapy begins close to menopause, while the endothelium is still healthy, or years later, after atherosclerotic changes have progressed.²

Race and Ethnicity Modified the Association

Race and ethnicity also modified the CVD effect of MHT initiation (P = .007). The aHR was 0.51 (95% CI, 0.33-0.81) for Black women, 1.07 (95% CI, 0.77-1.49) for white women, and 0.64 (95% CI, 0.25-1.67) for women of other races and ethnicities, a category that combined Chinese, Hispanic, and Japanese participants because of small event counts.¹

The authors noted that VMS are particularly prevalent among Black women, making this subgroup finding relevant to a population that has been underrepresented in prior randomized trials of MHT, most of which enrolled older, predominantly White participants.¹

Additional analyses in the SWAN cohort found no significant increase in venous thromboembolism among MHT initiators (aHR, 1.00; 95% CI, 0.39-2.58; P = .99), but did find an increased risk of breast cancer (aHR, 1.41; 95% CI, 1.00-1.98; P = .02). Among women who initiated MHT, the median duration of use was 3 years (Q1-Q3, 1-5).¹

Pharmacist Counseling Considerations

For pharmacists fielding questions from perimenopausal patients about hormone therapy, the study's authors were explicit that their findings should not be interpreted as support for using MHT to prevent cardiovascular disease. The data are observational, and the authors cautioned that residual confounding—particularly unmeasured VMS severity, which could influence both the decision to start MHT and CVD risk—may still be biasing the results.¹

Current guidance from the North American Menopause Society similarly does not recommend hormone therapy for coronary heart disease prevention, though it acknowledges that individualized use may be considered in women younger than 60 years and within 10 years of their final menstrual period if no contraindications are present.³

Pharmacists counseling patients on MHT should continue to weigh the elevated breast cancer risk identified in this analysis alongside any potential cardiovascular signal and should reinforce that the primary, guideline-supported indication for MHT remains symptom relief—not cardiovascular risk reduction. The authors called for randomized clinical trials specifically designed to test MHT's cardiovascular effect in perimenopausal women with VMS, noting that existing trials such as the Women's Health Initiative largely excluded this population.¹

REFERENCES

1. Wang Z, Swanson SA, Brooks MM, et al. Menopausal hormone therapy and cardiovascular risk in midlife women with vasomotor symptoms. JAMA Intern Med. Published online September 8, 2026. doi:10.1001/jamainternmed.2026.2922

2. Hodis HN, Mack WJ. Menopausal hormone replacement therapy and reduction of all-cause mortality and cardiovascular disease: it's about time and timing. Cancer J. 2022;28(3):208-223. doi:10.1097/PPO.0000000000000591

3. Buzduga CM, Bobu AM, Covali R, et al. Menopausal hormone therapy and cardiovascular risk: current evidence and clinical implications. Med Sci (Basel). 2026;14(2):298. doi:10.3390/medsci14020298