Elinzanetant improves sleep disturbances independent of improvements in vasomotor symptoms, according to data presented at The Menopause Society 2025 Annual Meeting.

Elinzanetant is a nonhormonal drug that the US Food and Drug Administration approved October 24 to treat hot flashes and night sweats. Data from 1898 women enrolled in the four randomized controlled OASIS trials showed that elinzanetant reduced the frequency and severity of vasomotor symptoms not only in postmenopausal middle-aged women but also, in one trial, in women aged 18-70 who had HR+ breast cancer, were receiving endocrine therapy, and were experiencing at least 35 moderate-to-severe vasomotor symptoms per week. 

"These findings highlight the potential for elinzanetant to improve sleep through mechanisms beyond vasomotor symptom alleviation and support the notion that sleep disturbances in menopause are not solely caused by vasomotor symptoms," Pauline Maki, PhD, told attendees. "Further research is warranted to elucidate the pathways through which elinzanetant exerts its direct effects on sleep." 

Maki, a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois in Chicago, presented pooled data from 1345 women enrolled across three phase 3 trials and one phase 2 trial that compared 120 mg of elinzanetant to placebo over 12 weeks. Two of the phase 3 trials, OASIS-1 and OASIS-2, included postmenopausal women who reported at least 50 vasomotor symptoms per week. OASIS-3 included postmenopausal women who reported any bothersome vasomotor symptoms, regardless of frequency. While none of these trials required participants to report sleep disturbances, the phase 2 NIRVANA trial included postmenopausal women with at least 20 vasomotor symptoms per week as well as sleep disturbances. 

Combining participants across the four trials, 668 women received 120 mg of elinzanetant and 677 women received placebo. All women documented their vasomotor symptoms twice a day and completed the PROMIS SD-SF-8b sleep assessment at baseline and weeks 1, 2, 3, 4, 8, and 12. Researchers used a longitudinal causal mediation analysis to understand the total treatment effect and the effect on sleep independent of reduction in nighttime vasomotor symptoms.

At baseline, women reported an average of 4.8 moderate-to-severe vasomotor symptoms at night and their sleep score averaged 59.6. Overall, women receiving elinzanetant experienced a 4.9-point improvement in their sleep scores compared to those receiving placebo. When taking into account changes due to vasomotor symptoms, however, researchers calculated that 2.25 of those points were due to improvements in symptoms while 2.67 points occurred directly because of elinzanetant separate from improvements in night sweats.

Overall, researchers calculated that 54.3% of the improvement in sleep disturbances was directly due to elinzanetant even without vasomotor symptom improvements. 

"It's very exciting to have another option for people who either don't want to be on hormone therapy or have a contraindication to being on hormone therapy," Monica Christmas, MD, an associate professor of obstetrics and gynecology and director of the Menopause Program at the University of Chicago Medicine, told Medscape Medical News. Christmas, who is also associate medical director for The Menopause Society, was not involved in any of the elinzanetant clinical trials, and said the recent approval of the drug was "huge" in providing women with more choices. 

"One of the nice things about this is that sleep was improved even outside of correcting for vasomotor symptoms," Christmas said. She found the safety profile of elinzanetant reassuring as well. 

Another important thing about this, Christmas said, "is that they didn't show in their safety data that there were the same hepatic concerns" as those seen with fezolinetant, the only other approved nonhormonal drug in the same class as elinzanetant. Both drugs are neurokinin-targeted therapies, with fezolinetant targeting the NK-3 receptor and elinzanetant targeting the NK-3 and NK-1 receptors in the brain.

With fezolinetant, you have to check a woman's liver function at baseline, then every month for the first 3 months, and then every 3 months for the rest of the year, Christmas explained. "With elinzanetant, because they didn't show the same liver concerns, the recommendation is just to check liver function at baseline and at 3 months," she added. Mild elevations in alanine aminotransferase or aspartate aminotransferase are not necessarily contraindications, Christmas noted. If there are no changes at 3 months, there is no indication for further testing.

Adding to the safety profile, "this one was also studied in women with a history of breast cancer," unlike fezolinetant, Christmas added.

The research was funded by Bayer. Maki has received personal fees from Astellas, Bayer, and Pfizer, and holds equity in Respin, Midi Health, and Estrigenix. Christmas has given lectures for FertilityIQ and had no other disclosures. 

Tara Haelle is a science/health journalist based in Dallas.