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The American College of Physicians recommends menopausal hormone therapy as first-line treatment for vasomotor symptoms such as hot flashes and night sweats. The guidance lists selected SNRIs as second-line options and several other medicines as third-line treatments, while noting that evidence is limited for some patient groups and treatments.
The American College of Physicians (ACP) recommends menopausal hormone therapy as the first-line medicine for vasomotor symptoms, including hot flashes and night sweats. The new clinical guideline specifies estrogen with progestogen for women with a uterus and estrogen alone for those without one, while setting out other medicines for patients who cannot use or do not tolerate hormone therapy.
The ACP rates both first-line recommendations as strong recommendations based on high-certainty evidence. The guidance was written by Amir Qaseem, MD, PhD, MHA, and colleagues and published in Annals of Internal Medicine. It addresses pharmacologic treatment of vasomotor symptoms, rather than every aspect of menopause care.
For patients with a contraindication to hormone therapy or who cannot tolerate it, the guideline places the serotonin-norepinephrine reuptake inhibitors desvenlafaxine and venlafaxine in the second line. The ACP bases that recommendation on moderate-certainty evidence. Third-line choices include the selective serotonin reuptake inhibitors escitalopram and paroxetine, and gabapentin, supported by low-certainty evidence; it also lists the neurokinin receptor antagonists fezolinetant and elinzanetant, supported by moderate-certainty evidence.
The recommendations draw on a systematic review and meta-analysis by Susan Diem, MD, MPH, of the VA Health Care System in Minneapolis, and colleagues, also published in the journal. The researchers included 90 trials reported in 102 publications. The trials ran from 1980 to 2024, lasted at least eight weeks, and had a median treatment duration of 12 weeks. Most enrolled healthy, postmenopausal white women ages 49 to 57 who experienced several vasomotor episodes a day.
How the Treatment Order Affects Care
The guideline gives clinicians and patients a clearer order for discussing medicines when hot flashes or night sweats disrupt daily life. It puts hormone therapy at the top of the treatment pathway while naming alternatives for people who cannot take it or find it intolerable. The ACP also encourages clinicians to start conversations about menopause and provide education, according to an accompanying editorial by Stephanie Faubion, MD, MBA, and Regina Castaneda, MD, of the Mayo Clinic in Jacksonville, Florida.
The recommendation arrives after years in which concerns about potential harms contributed to reduced hormone therapy use. The ACP’s ranking reflects its assessment of evidence for symptom treatment; it does not mean every patient is a candidate. Individual medical history and contraindications remain relevant, and the guideline’s evidence base does not answer every question for higher-risk or less-studied groups.
The review found the largest reductions in symptom frequency with estrogens, with or without progestogens, oxybutynin, and NK-receptor antagonists. It also reported modest improvements in menopause-related quality of life with estrogens, NK-receptor antagonists, SNRIs, and SSRIs. These findings describe outcomes across the included studies and do not establish that every treatment will work the same way for every patient.
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Evidence Behind the New Guidance
Menopausal hormone therapy has long been used to treat vasomotor symptoms. Use fell after findings from the Women’s Health Initiative (WHI) were associated with boxed warnings and concerns about cardiovascular disease and breast cancer. More recently, the FDA removed those warnings, and reanalyses of WHI data have suggested more favorable outcomes for women closer to menopause. The supplied report does not detail the FDA action’s timing or scope.
In 2022, the Menopause Society said the balance of benefits and risks is favorable for treating vasomotor symptoms in women younger than 60 or within 10 years of menopause onset who have no contraindications. That position statement is relevant context, but it is separate from the ACP’s new guideline.
The ACP review searched Embase, Cochrane, and Medline through March 3, 2026. Only eight studies focused on perimenopausal women. Trials commonly excluded people with a history of breast cancer, endometrial hyperplasia or cancer, cardiovascular disease, stroke, or venous thromboembolism. Compounded estrogens were not evaluated. The evidence also included older trials more likely to assess high-dose estrogen and newer studies more likely to assess nonhormonal medicines.
““It is therefore noteworthy that the guideline encourages clinicians to proactively initiate conversations about menopause and provide education.””
— Faubion and Castaneda
Who the Trials Left Out
The evidence is less representative of patients with conditions that can affect whether hormone therapy is appropriate. Because many trials excluded people with breast cancer, cardiovascular disease, stroke, blood clots, or endometrial conditions, the results cannot settle treatment choices for those groups. The editorialists called for research focused on people excluded from the current evidence base, whose care should not rely only on extrapolating from healthier trial participants.
The review found insufficient evidence to determine how treatment results differ by age, race, ethnicity, or menopausal status. The supplied report also says more research is needed on newer nonhormonal medicines and in populations with contraindications to hormone therapy. Evidence for oxybutynin came from a small trial and was rated low to moderate certainty, so its effects and harms require further study. The source material does not specify how the guideline addresses every patient’s individual risk profile.
Further Research and Clinical Discussion
The guideline authors say more evidence is needed on newer nonhormonal agents and on treatment for patients who cannot use hormone therapy. Research that includes more varied patient populations, including people with medical conditions that led to trial exclusions, could help clarify how benefits and harms differ across clinical circumstances.
For now, the ACP guidance gives clinicians a treatment sequence to discuss with patients experiencing vasomotor symptoms: hormone therapy first when appropriate, selected SNRIs second when first-line treatment is contraindicated or not tolerated, and listed SSRIs, gabapentin, or NK-receptor antagonists as third-line options. The next step for an individual patient is a clinical discussion about symptoms, medical history, contraindications, preferences, and the available evidence.
Key Questions
What does the ACP recommend first for menopausal hot flashes and night sweats?
The ACP recommends menopausal hormone therapy as first-line pharmacologic treatment for vasomotor symptoms. It recommends estrogen with progestogen for women with a uterus and estrogen alone for those without one.
Which medicines are listed if hormone therapy is not suitable or tolerated?
The guideline lists desvenlafaxine or venlafaxine as second-line options for people with contraindications to or intolerance of first-line treatment. Third-line options include escitalopram, paroxetine, gabapentin, fezolinetant, and elinzanetant.
Does the guideline mean hormone therapy is right for every patient?
No. The recommendation identifies a first-line treatment based on the guideline’s evidence review, but medical history and contraindications still matter. The review included limited evidence for people with several conditions that commonly excluded them from trials.
How broad was the evidence review?
The review included 90 trials reported in 102 publications, with studies searched through March 3, 2026. Most participants were healthy, postmenopausal white women ages 49 to 57, and only eight studies focused on perimenopausal women.
Source: rss
