Understanding Hormone Therapy

Hormone therapy (HT), also known as hormone replacement therapy, involves giving estrogen, sometimes combined with progestin, to replace the hormones that decline after menopause. It’s mainly prescribed to relieve vasomotor symptoms such as hot flashes, night sweats, and sleep disturbance, as well as to help maintain bone health.

But over the years, questions have persisted about whether HT increases a woman’s risk of heart attack, stroke, or other cardiovascular events. Earlier studies gave mixed results, often depending on the woman’s age and how long it had been since menopause started.

What the New JAMA Study Found

A recent secondary analysis of two Women’s Health Initiative (WHI) randomized controlled trials, published in JAMA Internal Medicine in September 2025, revisited this issue with updated methods. The trials followed over 27,000 postmenopausal women for nearly two decades.

Participants were randomly assigned to receive:

• Oral conjugated equine estrogens (CEE) 0.625 mg daily, or
• CEE combined with medroxyprogesterone acetate (MPA) 2.5 mg daily,  compared with a placebo.

Researchers analyzed outcomes by age group, specifically 50 – 59, 60 – 69, and 70 – 79 years, and by whether women had vasomotor symptoms (VMS) at baseline.

Main Findings

• Among women aged 50 – 59, hormone therapy significantly improved vasomotor symptoms and did not increase overall cardiovascular risk compared to placebo.
• In contrast, among women aged 70 – 79, hormone therapy was associated with a notable rise in cardiovascular events, including heart attacks and strokes, especially among those who still had VMS.
• For women in the 60 – 69 age range, results were mixed showing a slight increase in risk, but not as pronounced as in the oldest group.

Why Age Matters

Scientists believe the timing of therapy plays a crucial role often called the “timing hypothesis.” Younger postmenopausal women (usually under 60 or within 10 years of menopause onset) generally have healthier blood vessels and less atherosclerosis. When estrogen is reintroduced early, it can actually help maintain vessel flexibility and normal lipid balance.

However, in older women particularly those who start therapy many years after menopause, estrogen may instead destabilize existing plaques or increase clotting tendencies, raising cardiovascular risk.

Benefits Beyond Symptoms

Beyond hot flashes, hormone therapy in younger women can help:

• Improve sleep and mood, when these are linked to menopausal changes
• Prevent bone loss and reduce fracture risk
• Possibly improve quality of life and sexual function when used short term under medical supervision

However, the same benefits must always be weighed against potential risks such as blood clots, stroke, and breast cancer, which can increase with longer use or higher doses.

What Doctors Now Recommend

Based on the new findings, experts suggest the following practical guidance:

• Ideal window: Start hormone therapy before age 60 or within 10 years after menopause begins, if symptoms are moderate to severe.
• Avoid late initiation: Starting hormone therapy after age 70 is generally not advised due to higher cardiovascular risk.
• Use the lowest effective dose for the shortest duration needed to control symptoms.
• Consider delivery method: Transdermal (patch or gel) estrogen may carry lower clotting risk than oral forms.
• Regular check-ups: Women on hormone therapy should have routine monitoring of blood pressure, cholesterol, and breast health.

The Bottom Line

Hormone therapy remains a safe and effective option for younger postmenopausal women struggling with symptoms that affect daily life. But it’s not for everyone, and age and heart health must guide the decision.

Women should discuss with their doctor:

• How long it’s been since menopause began
• Any personal or family history of heart disease, stroke, or cancer
• The right hormone type, dose, and form for their individual needs

The key message from the new study is clear: when started early, hormone therapy can help but when started late, it may harm.

References:

• JAMA Internal Medicine. (2025). “Age-Stratified Cardiovascular Outcomes with Menopausal Hormone Therapy: Secondary Analysis of the Women’s Health Initiative Trials.”
• National Institutes of Health, Women’s Health Initiative Program.
• North American Menopause Society (NAMS) 2023 Position Statement on Hormone Therapy.