The American College of Physicians (ACP) has released a new clinical guideline recommending estrogen, alone or combined with progestogen, as the first-line treatment for women experiencing hot flashes and night sweats during and after menopause.

In the guideline, published online in Annals of Internal Medicine, the ACP provides a practical treatment sequence from estrogen in combination with progestogen for women with a uterus or estrogen monotherapy for women without a uterus as first-line treatment for menopausal vasomotor symptoms (VMSs), based on a high level of evidence outlined in an accompanying evidence review. Second-line recommendations include desvenlafaxine or venlafaxine, and third-line recommendations include escitalopram or paroxetine, gabapentin, elinzanetant or fezolinetant, with evidence ranging from low to moderate certainty.

The new guideline mainly aligns with previous recommendations from the American College of Obstetricians & Gynecologists and from the Menopause Society.

The American College of Obstetricians & Gynecologists published a practice bulletin in 2014, affirmed in 2024, that supports the use of estrogen to manage VMSs. The bulletin also noted that selective serotonin reuptake inhibitors ( SSRIs ), selective serotonin and norepinephrine reuptake inhibitors (SNRIs), clonidine, and gabapentin can be used to relieve VMSs as alternatives to hormone therapy. The Menopause Society published a position statement with similar support for hormone therapy for VMSs in 2022.

VMSs can last for years, with a major impact on health and quality of life, said Amir Qaseem, MD, PhD, MHA, chief science officer at ACP in Philadelphia, and an author of the paper. Although VMSs can affect up to 80% of women and may persist after menopause, patients experiencing VMSs may not raise the topic with their physicians, and may remain untreated or undertreated despite many evidence-based options available, Qaseem said. “Ask your female patients in their forties about menopausal vasomotor symptoms, provide education regarding what to expect, and treatment options; it is an important first step,” Qaseem noted.

Limitations and Considerations

The ACP guideline is distinctive in its emphasis on informed decision-making, with discussion not only of potential benefits, harms, contraindications, and comorbid conditions but also a patient’s values and preferences, financial burden, and access to and availability of treatments, Regina Castaneda, MD, a postdoctoral fellow at the Mayo Clinic, and Stephanie S. Faubion, MD, MBA, professor and chair in the Department of Medicine at the Mayo Clinic, Jacksonville, Florida, and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote in an accompanying editorial.

“Developed for clinicians, anchored in outcomes prioritized by patients, and accompanied by explicit assessments of certainty of evidence, the guideline offers a valuable framework for translating evidence into individualized treatment decisions,” they said. However, “[a]lthough the guideline is primarily focused on the management of VMS, other clinical considerations appropriately influence treatment,” the authors noted. “For instance, a patient with concurrent depression may reasonably favor a selective serotonin reuptake inhibitor despite its third-line designation, whereas the skeletal benefits of estrogen therapy may favor its use in women with osteoporosis,” they explained.

Evolving Options

As the treatment of VMS s of menopause is initiated not only by ob/gyns but also by other primary care practitioners, it is especially important to provide uniform and tiered guidelines allowing step-by-step management of the condition, said Aleksandr M. Fuks, MD, FACOG, professor and chair in the Department of Ob/Gyn at the Quillen College of Medicine, East Tennessee State University, Johnson City.

Fuks, who was not involved in developing the guideline, said, “I believe the recommendations are consistent with what many clinicians experienced in menopause care are already doing following the recommendations of the Menopause Society: estrogen/estrogen-progestin therapy being defined as the most effective treatment and recognizing SSRIs/SNRIs, gabapentin, and fezolinetant among evidence-based nonhormonal approaches.”

However, the ACP guideline is distinctive in its formal Grading of Recommendations, Assessment, Development and Evaluation-based hierarchy of treatment recommendations combined with explicit consideration of economic evidence and patient values, Fuks noted. The guideline moves beyond asking simply whether a treatment works to considering whether its benefits, harms, cost, availability, and financial burden make sense for an individual patient, he said.

The challenge is in the individualization of treatment, as patients experiencing VMSs differ substantially in age, time since menopause, symptom severity, cardiovascular and oncologic risk, concurrent medications, and preferences, said Fuks. For those interested in the newer neurokinin receptor antagonists, insurance coverage and prior authorization requirements may limit access, but generic SSRIs, SNRIs, and gabapentin are generally more accessible, he said.

Research Gaps and Next Steps

Longer-term randomized trials are needed to inform practice, said Fuks. Most of the trials included in the guideline analysis were relatively short, with a median of about 12 weeks, he noted. “This makes them poorly suited to identifying uncommon but clinically important outcomes such as breast cancer, endometrial cancer, cardiovascular events, stroke, and venous thromboembolism. Longer follow-up is especially important because many patients use these therapies for years,” he said.

Data from head-to-head comparative effectiveness trials, including comparisons among different estrogen doses and formulations and between hormonal and nonhormonal therapies, are significantly lacking, Fuks added.

“Future research should also focus on the optimal age for initiating therapy, whether there should be an upper age limit, optimal treatment duration, and the long-term safety of different estrogen formulations and routes,” said Fuks. “The guideline also identifies a need for better evidence stratified by age, race, ethnicity, menopausal stage, and baseline risk for serious adverse outcomes, as well as need for comparative economic analysis of different modalities, focusing on benefits as a function of acceptable burden, risk, and cost,” he said.

Disclosures for the authors and the editorial are available in the original study and editorial publications. Fuks had no financial conflicts to disclose.