Nonhormonal Therapies Transform Hot Flash Treatment in Menopause | HCPLive

In 2025, major shifts to the landscape of non-hormonal therapies available for treating vasomotor symptoms (VMS) in postmenopausal women were reported, the most recent being the FDA approval of elinzanetant (Lynkuet) in this population on October 24, 2025.1

Elinzanetant, a neurokinin receptor antagonist, represents a method of treatment which, according to JoAnn V. Pinkerton, MD, division director of midlife health at UVA Health, has begun to reshape the VMS landscape.2 Thermoregulatory instability during menopause has been linked to overactivity in certain hypothalamic neurons caused by declining estrogen levels.

Risks associated with hormonal therapies have previously been reported to patients through boxed warnings on the products’ labeling.4 In the Women’s Health Initiative (WHI) trials, increased risks of stroke and breast cancer were reported in patients receiving menopausal hormonal therapy (MHT).

This revelation led to class-wide boxed warnings being added to MHT starting in 2003. However, the FDA noted that WHI participants had an increased age relative to the general population receiving therapy for hot flash relief, increasing their baseline risks.4

Compared to the mean age of 51 years in patients starting MHT, dementia findings in the WHI were based on women aged 65 to 79 years. The primary version of hormone therapy has also changed since this data was published, from oral conjugated equine estrogens plus medroxyprogesterone acetate to versions with transdermal estradiol, which reduces venous thrombosis risk.4Based on this information, the FDA announced actions to revise safety labelling for MHT on November 10, 2025. These changes included:4

• Removing warnings about cardiovascular disease, breast cancer, and dementia
• Removing most references to endometrial cancer
• Removing recommendations to use the lowest dose for the shortest duration

Currently, warnings about breast cancer risk remain for labeling outside of boxed warnings for systemic therapy. Further research is needed to understand the link between MHT and breast cancer.4

“It's important to note that we need more data to make up for the dearth of research in this domain and until we better understand the full impact of MHT on breast cancer risk, women with a personal history of breast cancer remain ineligible for MHT,” said Nora Lansen, MD, chief medical officer at Elektra Health.4

Clinical Evidence Supporting Fezolinetant

During the period of boxed warnings for hormonal options, multiple nonhormonal treatments rose in the vasomotor symptom landscape. At the 2023 ACOG Annual Clinical & Scientific Meeting, Genevieve Neal-Perry, MD, PhD, professor at the University of North Carolina at Chapel Hill, presented data regarding the safety and efficacy of fezolinetant.3

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Nonhormonal Therapies Transform Hot Flash Treatment in Menopause | HCPLive