Menopausal Hormone Therapy and Cardiovascular Diseases in Women With Vasomotor Symptoms: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials
Errata to this article were published (JAMA Intern Med, 1 Nov 2025 ↗ · 1 Feb 2026 ↗)
Authors' conclusion
In this secondary analysis of 2 randomized clinical trials, among younger postmenopausal women aged 50 to 59 years, both CEE alone and CEE plus MPA reduced VMS without significantly affecting ASCVD risk. In women with VMS 70 years and older, risks for ASCVD were increased in both trials.
Study context
- Population
- Postmenopausal women aged 50 to 79 years; Atherosclerotic CVD (ASCVD) results in women with moderate or severe vasomotor symptoms (VMS)
- Participants
- 27,347 women
- Comparison
- Conjugated equine estrogens (CEE) alone or CEE plus medroxyprogesterone acetate (MPA) vs placebo
- Primary endpoint
- ASCVD (nonfatal MI, hospitalization for angina, coronary revascularization, ischemic stroke, PAD, carotid artery disease or cardiovascular disease (CVD) death)
Methodological details40 US clinical centres, subgroup analysis by age in women with VMS, Data collected November 1993 to September 2012; analysed December 2024 to May 2025
- 40 US clinical centres
- Subgroup analysis by age in women with VMS
- Data collected November 1993 to September 2012; analysed December 2024 to May 2025
Primary result
As reported in the abstract
ASCVD in women with moderate or severe VMS, by age
Each group vs placeboHazard ratio (95% CI)
CEE aloneage 50-59 years
0.85(0.53–1.35)
CEE plus MPAage 50-59 years
0.84(0.44–1.57)
CEE aloneage 60-69 years
1.31(0.90–1.90)
CEE plus MPAage 60-69 years
0.84(0.51–1.39)
CEE aloneage ≥70 years; 217 excess events per 10 000 person-years; interaction P for trend = .03
1.95(1.06–3.59)
CEE plus MPAage ≥70 years; 382 excess events per 10 000 person-years; interaction P for trend = .02
3.22(1.36–7.63)
Further findings
| Outcome | RR (95% CI) | |
|---|---|---|
| VMS reduction, CEE alone trialCEE alone vs Placebo · overall; reduced VMS by 41% across all age groups | 0.59 (0.53–0.66) | |
| VMS reduction, CEE plus MPA trial, by ageCEE plus MPA vs Placebo · age 50-59 years | 0.41 (0.35–0.48) | |
| VMS reduction, CEE plus MPA trial, by ageCEE plus MPA vs Placebo · age 60-69 years | 0.72 (0.61–0.85) | |
| VMS reduction, CEE plus MPA trial, by ageCEE plus MPA vs Placebo · age 70-79 years | 1.20 (0.91–1.59) | |
| 0.20.5125Relative risk (log scale) |
- VMS reduction, CEE plus MPA trial, by age: interaction P for trend < .001
Original publication
Menopausal Hormone Therapy and Cardiovascular Diseases in Women With Vasomotor Symptoms: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials. JAMA Intern Med. Published 1 November 2025. doi:10.
Summarised from the published abstract; every number is checked against it