ACP Guideline Recommends Hormonal Therapy as First-Line Treatment for Menopausal Vasomotor Symptoms

In a guideline published in Annals of Internal Medicine, the American College of Physicians (ACP) recommends hormonal therapy as first-line treatment for perimenopausal and postmenopausal females seeking treatment of menopausal vasomotor symptoms (VMS).

VMS, generally defined as hot flashes and night sweats, are the most common symptoms during perimenopause, affecting up to 80% of females, according to the guideline. The ACP Clinical Guidelines Committee developed the recommendations from systematic reviews of effectiveness, harms, patient values and preferences, and economic evidence.

ACP recommends that clinicians initiate estrogen in combination with progestogen in females with a uterus or estrogen monotherapy in females without a uterus (strong recommendation; high-certainty evidence). The committee cited evidence that benefits exceeded harms and cost-effectiveness analyses showing high value. Compared with placebo, both regimens reduced VMS severity and frequency (moderate- to high-certainty evidence).

For females who have contraindications to or do not tolerate first-line therapy, ACP suggests the serotonin–norepinephrine reuptake inhibitors desvenlafaxine or venlafaxine as second-line treatment (conditional recommendation; moderate-certainty evidence). As third-line options, ACP suggests the selective serotonin reuptake inhibitors escitalopram or paroxetine, gabapentin, or the neurokinin receptor antagonists elinzanetant or fezolinetant (conditional recommendation). The committee ranked neurokinin receptor antagonists third line, despite benefits exceeding harms, because fezolinetant was judged low value and elinzanetant has a higher wholesale acquisition cost than fezolinetant.

Most eligible trials were short (median, 12 weeks) and small, limiting assessment of rare harms, the guideline notes. Longer-term nonrandomized studies associate estrogen-containing treatment with increased stroke and venous thromboembolism risk and combined estrogen-progestogen treatment with higher breast cancer risk. ACP states that treatment selection should use informed decision-making that addresses benefits, harms, contraindications, comorbid conditions, values and preferences, financial burden, and access. ACP President Jan K. Carney, MD, MPH, said in a news release that many females "silently suffer" from VMS without receiving effective treatment.

Sources: Qaseem A, Mackey K, Yost J, et al.; Clinical Guidelines Committee of the American College of Physicians. Pharmacologic treatments for females with menopausal vasomotor symptoms: a clinical guideline from the American College of Physicians. Ann Intern Med. Published online October 6, 2026. doi:10.7326/ANNALS-26-01205

American College of Physicians. ACP recommends hormonal therapy as a first-line treatment for menopausal vasomotor symptoms. News release. American College of Physicians; October 5, 2026. Accessed October 7, 2026.