ACP recommends hormone therapy first for menopausal hot flashes

Clinical takeaway: For patients seeking drug treatment for menopausal vasomotor symptoms, ACP recommends estrogen plus a progestogen for those with a uterus and estrogen alone for those without one as first-line therapy. Treatment should be individualized around contraindications, comorbidities, patient preferences, cost, and access.

The American College of Physicians (ACP) has issued new guidance for managing hot flashes and night sweats in perimenopausal and postmenopausal patients. VMS affects up to 80% of patients during perimenopause, can persist into the postmenopausal years, and may disrupt daily activities and quality of life.

ACP strongly recommends estrogen plus progestogen for patients with a uterus and estrogen monotherapy for those without a uterus, both supported by high-certainty evidence. For patients who cannot use or tolerate hormone therapy, second-line therapy includes the SNRIs desvenlafaxine or venlafaxine, followed by the SSRIs escitalopram or paroxetine, gabapentin, or the neurokinin receptor antagonists (NKRAs) elinzanetant or fezolinetant as third-line options. Treatment efficacy should be assessed after 8 to 12 weeks.

An accompanying systematic review of 90 randomized trials found that estrogen with or without a progestogen reduced VMS frequency and severity and improved quality of life. Nonhormonal agents also reduced VMS frequency, with some showing additional benefits for quality of life and sleep.

The guideline builds on earlier hormone and nonhormone therapy guidance from The Menopause Society, incorporating newer evidence on neurokinin receptor antagonists and providing a clearer treatment framework. Cost and access also factor into treatment selection; the evidence review found that estrogens with and without progestogens offered high economic value, while higher costs contributed to the placement of NKRAs as third-line therapy.

For estrogen therapy, efficacy did not vary by route, although comparative harms could not be reliably evaluated. Higher doses were more effective than lower doses for VMS, but their overall benefit-harm balance remains uncertain. The optimal duration of hormone therapy is unknown; although 3 to 5 years is common in clinical practice. Clinicians should regularly reevaluate benefits and risks to determine when to discontinue treatment.

The accompanying editorial calls the guidance a “rigorous evidence synthesis that offers a strong foundation for individualizing treatment of menopausal women and clarifies evidence gaps that remain.” It emphasizes that limited comparative harms data mean the similar efficacy observed across estrogen routes should not be interpreted as evidence of equivalent safety.

Key recommendations

• First line: Estrogen plus progestogen for patients with a uterus or estrogen monotherapy for those without a uterus. Strong recommendation; high-certainty evidence.
• Second line: SNRIs (desvenlafaxine or venlafaxine). Conditional recommendation; moderate-certainty evidence.
• Third line: Conditional recommendation, with options including:
• SSRIs (escitalopram or paroxetine): low-certainty evidence
• Gabapentinoid (gabapentin): low-certainty evidence
• Neurokinin receptor antagonists (elinzanetant or fezolinetant): moderate-certainty evidence
• Treatment selection: Use informed decision-making that considers benefits and harms, contraindications, comorbidities, patient values and preferences, financial burden, access, and treatment availability.

Source: Qaseem A, et al. (2026 Oct 6) Ann Intern Med. Pharmacologic Treatments for Females With Menopausal Vasomotor Symptoms: A Clinical Guideline From the American College of Physicians