Hormones Work Best for Menopause Hot Flashes

Estrogen-based therapy reduced menopausal hot flashes and night sweats most consistently, but long-term harms remain uncertain.
*Systematic review and meta-analysis of randomized trials; Level 1a.

Citation

Diem S, Landsteiner A, Langsetmo L, et al. Pharmacologic Treatments for Female Menopausal Vasomotor Symptoms. Ann Intern Med. Published October 6, 2026. doi:10.7326/ANNALS-26-00943

Background

Hot flashes and night sweats are common during and after menopause and can impair sleep and daily life. This review informed American College of Physicians guidance on drug treatment choices.

Patients

Perimenopausal or postmenopausal females with bothersome symptoms. Many trials excluded prior breast cancer, womb lining cancer or overgrowth, heart disease, stroke, or blood clots.

Intervention

Estrogen, estrogen plus progestogen, conjugated estrogen with bazedoxifene, progestogen alone, oxybutynin, gabapentin, fezolinetant or elinzanetant, venlafaxine or desvenlafaxine, escitalopram or paroxetine.

Control

Mostly placebo; few head-to-head comparisons.

Outcome

Daily symptom frequency, symptom severity (0 to 3), menopause-related quality of life, sleep quality, serious harms, and womb lining safety.

Follow-up Period

Median 12 weeks; range 8 to 374 weeks.

Results

Treatment vs placebo Daily episodes Severity
Estrogen 2.63 fewer (95% CI 2.16 to 3.10 fewer) 0.53 lower (95% CI 0.37 to 0.69 lower)
Estrogen plus progestogen 3.27 fewer (95% CI 2.72 to 3.81 fewer) 0.79 lower (95% CI 0.56 to 1.03 lower)
Estrogen plus bazedoxifene 1.77 fewer (95% CI 0.29 to 3.25 fewer) 0.65 lower (95% CI 0.26 to 1.04 lower)
Oxybutynin 4.79 fewer (95% CI 3.18 to 6.40 fewer) 0.97 lower (95% CI 0.64 to 1.30 lower)
Fezolinetant or elinzanetant 2.09 fewer (95% CI 1.55 to 2.62 fewer) Not clinically important
Gabapentin 1.31 fewer (95% CI 1.01 to 1.60 fewer) Not clinically important

Estrogen effects increased with dose, with no clear difference by route. Quality of life improved with estrogen-based therapy, fezolinetant or elinzanetant, antidepressants, and related drugs. Sleep improved mainly with nonhormonal options. Serious harms were uncommon but poorly studied. A small meaningful change was defined as 1 fewer daily episode or 0.4 severity points.

Limitations

Most trials were short, enrolled generally healthy White postmenopausal women, and were not designed to detect rare or delayed harms.

Funding

American College of Physicians; guideline-related funding.

Clinical Application

Use estrogen-based therapy for eligible patients seeking strongest symptom relief; discuss risks and consider nonhormonal options when hormones are unsuitable.