Menopause Experts Release Guidance on Non-Hormone Therapy for Hot Flashes

CHICAGO — A multidisciplinary group of menopause experts developed new comorbidity-specific guidance on non-hormone therapy for moderate-to-severe vasomotor symptoms.

For patients whose primary menopausal symptoms are hot flashes and night sweats, first-line neurokinin (NK)-receptor antagonists are recommended, with alternative or second-line treatment options including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, and oxybutynin, noted JoAnn Pinkerton, MD, of the University of Virginia Health System in Charlottesville, at ENDO 2026, the annual meeting of the Endocrine Society.

NK-receptor antagonists, like fezolinetant (Veozah) and elinzanetant (Lynkuet), have strong evidence for managing hot flashes, Pinkerton said, and while access is limited, it is improving.

The group opted not to recommend clonidine due to rebound hypertension, as well as most herbal and over-the-counter products, since better options are available.

Pinkerton stressed that hot flashes are common and disruptive to menopausal women, and hormone therapy is contraindicated for or declined by many patients.

“Many non-hormone options exist, but we really didn’t have any U.S. comorbidity-specific guidance,” she said. “We thought that was really lacking.”

Rachel Weinerman, MD, an ob/gyn and reproductive endocrinologist at Case Western Reserve University in Cleveland, told MedPage Today that for women who are not good candidates for hormone therapy, treatment options tend to target specific symptoms.

She noted that some of these options, like NK-receptor antagonists, are newer, and with options evolving, it can be confusing for clinicians.

“These new guidelines nicely address this need by providing first- and second-line options for each symptom. That way, women and physicians can prioritize which symptom they would like to address and find the best-targeted treatment option,” Weinerman said. For some women, a combination of therapies might be appropriate.

“As there is a general lack of knowledge about menopause among physicians, I hope these guidelines will help make it clearer for patients and their doctors how to address the symptoms of menopause in a way that prioritizes individual patient needs,” she added.

To create this consensus-based comorbidity-specific guidance and a menopause medical eligibility criteria (MenoMEC) tool, a group of 15 multidisciplinary experts, representing ob/gyn, endocrinology, primary care, and other specialties, convened a modified Delphi panel. They conducted a systematic review of U.S. guidelines from 2014 to 2024, and an online survey. To refine recommendations, agreement at or exceeding 70% was considered consensus.

Recommendations for initiating or continuing transdermal or oral hormone therapy, approved non-hormone therapy, and off-label non-hormone therapy for the treatment of vasomotor symptoms were developed with consideration of 13 comorbidities, including age, smoking, atherosclerotic cardiovascular disease/PREVENT 10-year risk scores, known cardiovascular disease, metabolic conditions, risk of breast cancer, history of breast cancer, history of gynecologic cancer, history of other cancers, gastroenterological conditions, neurological conditions, thrombosis, and autoimmune disease.

They used a 4-point scale to rate the therapy options in the presence of these comorbidities: no restrictions, advantages generally outweigh theoretical or proven risks, theoretical or proven risks usually outweigh the advantages, and unacceptable health risk.

Oral hormone therapy was deemed unacceptable for those initiating treatment at age 70 or older. As expected, Pinkerton and colleagues determined that hormone therapy was unacceptable or risky for those with various heart disease risks and conditions, for some patients with a history of gynecologic or breast cancers, and for some with metabolic or gastroenterological conditions.

As a whole, most non-hormone therapies were given the green light for patients who had contraindications to hormone therapy — with a few exceptions.

Off-label non-hormone therapy (gabapentin and oxybutynin) was deemed risky for this group, while on-label non-hormone therapy was not recommended for patients with some gastroenterological conditions, including cirrhosis and acute hepatitis.

Pinkerton said the group is planning to create an app and in-clinic reference card serving as a decision support tool modeled after the World Health Organization’s medical eligibility criteria for contraception. She noted that all treatment decisions warrant discussion with relevant clinicians and may vary based on patients’ medications and other factors.