ACP Now Recommends Hormone Therapy First for Menopausal Hot Flashes

Menopausal hormone therapy has reclaimed its position as the recommended first-line treatment for vasomotor symptoms, according to sweeping new guidelines from the American College of Physicians published in the Annals of Internal Medicine. The guidance reflects a significant reversal in clinical thinking that had been shaped for two decades by safety concerns originally raised by the Women's Health Initiative study.

The core recommendation is strong and grounded in high-certainty evidence: women with a uterus should receive combined estrogen and progestogen therapy, while women without a uterus can use estrogen alone. This distinction is important because unopposed estrogen in women with a uterus raises endometrial cancer risk, making progestogen co-administration essential.

For women who cannot tolerate or have contraindications to hormone therapy, the guidelines establish a clear hierarchy of alternatives. SNRIs — specifically desvenlafaxine and venlafaxine — are designated second-line options backed by moderate-certainty evidence. Third-line choices include SSRIs such as escitalopram and paroxetine, gabapentin, and the newer NK receptor antagonists fezolinetant and elinzanetant. Evidence strength varies, with the NK antagonists carrying moderate-certainty support compared to lower certainty for SSRIs and gabapentin.

The reversal builds on the FDA's recent removal of cardiovascular and breast cancer warnings that had driven a steep decline in hormone therapy prescribing. Re-analyses of WHI data now suggest that women under 60 and within 10 years of menopause onset face a favorable risk-benefit profile — a conclusion already reflected in the Menopause Society's 2022 position statement. Vasomotor symptoms affect the majority of women during menopause and can significantly impair sleep, mood, and quality of life, making effective treatment a meaningful healthspan issue.

Editorialists from the Mayo Clinic welcomed the guideline's push for clinicians to proactively raise menopause discussions, noting that previous undertreatment stemmed from misconceptions rather than true risk. Caveats remain: evidence is thinner for populations with absolute contraindications to hormones, and longer-term data on the newest non-hormonal agents are still accumulating.