Avoid hormone therapy after age 70
In women with hot flashes and night sweats, starting menopausal hormone therapy at age 70 or older increased artery-related heart and stroke disease, despite symptom relief in younger women.
*Secondary analysis of randomized trials; Level 1b (OCEBM).

Citation

Rossouw JE, Aragaki AK, Manson JE, et al. Menopausal hormone therapy and cardiovascular diseases in women with vasomotor symptoms: a secondary analysis of the Women’s Health Initiative randomized clinical trials. JAMA Internal Medicine. 2025;185(11):1330-1339. doi:10.1001/jamainternmed.2025.4510

Background

Menopausal hormone therapy relieves hot flashes and night sweats, but many clinicians worry about heart and stroke risks, especially in older patients. This analysis examined whether these risks differ by age among women who had moderate or severe symptoms at baseline.

Patients

Postmenopausal women aged 50 to 79 years from 40 US centers (n=27,347). Excluded if they could not complete a 3-month washout from prior hormone therapy.

Intervention

Oral conjugated equine estrogens (0.625 mg/day) in women with hysterectomy, or the same estrogen plus medroxyprogesterone acetate (2.5 mg/day) in women with an intact uterus.

Control

Placebo.

Outcome

Primary: artery-related cardiovascular disease (composite of heart attack, angina admission, coronary procedures, ischemic stroke, peripheral artery disease, carotid artery disease, or cardiovascular death). Also assessed symptom improvement at 1 year.

Follow-up Period

Median 7.2 years (estrogen-alone trial) and 5.6 years (estrogen-plus-progestin trial).

Results

Finding (women with moderate/severe symptoms) Effect size Absolute harm
Age 70–79: estrogen alone vs placebo (primary outcome) Hazard ratio 1.95 (95% CI, 1.06–3.59) +217 events per 10,000 person-years (number needed to harm ≈46/year)
Age 70–79: estrogen + progestin vs placebo (primary outcome) Hazard ratio 3.22 (95% CI, 1.36–7.63) +382 events per 10,000 person-years (number needed to harm ≈26/year)
Analyses were intention-to-treat.

Limitations

This was a subgroup-focused secondary analysis; some estimates were imprecise, and multiple comparisons raise the chance of false-positive findings. Only fixed-dose oral regimens were studied, so results may not apply to other formulations or routes.

Funding

US National Heart, Lung, and Blood Institute; pills donated by Wyeth Ayerst.

Clinical Application

Use menopausal hormone therapy for bothersome symptoms mainly at ages 50–59; be cautious at 60–69; avoid starting it at 70+ due to higher cardiovascular harm.