JAMA Study: Hormone Therapy for Menopausal Symptoms Safe at 50-59, Raises Risks After 70 - Video

A secondary analysis of two randomized clinical trials found that conjugated equine estrogens (CEE) alone and CEE plus medroxyprogesterone acetate (MPA) reduced vasomotor symptoms (VMS) without raising ASCVD risk in postmenopausal women aged 50–59. However, in women aged 70 and older with VMS, ASCVD risks increased. Findings support HT use in women 50–59, caution for ages 60–69, and avoidance in those 70+.

Published in JAMA Internal Medicine, the investigation revisited data from the landmark Women’s Health Initiative (WHI) hormone therapy trials. Jacques E. Rossouw, MD, of the National Heart, Lung, and Blood Institute, and colleagues examined outcomes in 27,347 postmenopausal participants, aiming to clarify which women with moderate to severe VMS might safely benefit from hormone therapy (HT).

The analysis included women aged 50 to 79 years from 40 U.S. clinical centers who were followed for up to eight years. Participants received either daily conjugated equine estrogens (CEE) 0.625 mg alone, CEE combined with medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. The primary focus was the incidence of atherosclerotic cardiovascular disease (ASCVD), encompassing nonfatal heart attack, angina requiring hospitalization, coronary revascularization, ischemic stroke, peripheral arterial disease, carotid artery disease, or cardiovascular death.

The findings showed that Hormone therapy significantly relieved moderate or severe vasomotor symptoms (VMS) in women enrolled at baseline. CEE alone reduced VMS by about 41% across all age groups. The combination of CEE plus MPA showed the greatest benefit in younger women, with effectiveness declining with age. Relative risk reductions for VMS were 59% in women aged 50–59, 28% in women aged 60–69, and showed virtually no benefit in those aged 70–79. Cardiovascular outcomes demonstrated a clear age-related pattern.

These findings reinforce current guidance that favors menopausal hormone therapy for healthy, recently postmenopausal women suffering moderate to severe hot flashes or night sweats, while advising caution after age 60 and recommending against initiation after age 70. The authors note that only oral CEE and MPA were tested, and some subgroups were small, but emphasize that new large trials in this population are unlikely.

Ref: 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 Intern Med. Published online September 15, 2025. doi:10.1001/jamainternmed.2025.4510