Non-Hormonal Drugs Show Promise For Menopausal Sleep Disturbance
A new meta-analysis finds NK-receptor antagonists, non-hormonal medications for hot flashes, significantly improve sleep disturbances in menopausal women within four weeks.
New non-hormonal treatments for menopausal sleep disturbance show promising results in a recent meta-analysis. The review of seven clinical trials found that two medications, fezolinetant and elinzanetant, significantly improved sleep for women with moderate-to-severe vasomotor symptoms as early as four weeks.
The analysis pooled data from 3,184 women with an average age of 54.5. It included seven placebo-controlled trials: OASIS I, II, and III; SWITCH-1; DAYLIGHT; SKYLIGHT I and II (pooled); and Depypere 2019. Participants had a mean body mass index of 27.7. In the trials, 949 women took fezolinetant, 864 took elinzanetant, and 1,371 received a placebo.
The primary outcome was change on the PROMIS SD-SF-8b scale, where a lower score indicates less sleep disturbance. Sleep improvement was measured at 4 weeks and sustained through 24 weeks. Elinzanetant showed greater efficacy than fezolinetant at both the 4-week and 12-week marks.
| Medication | 4-Week Efficacy (SMD) | 12-Week Efficacy (SMD) |
|---|---|---|
| Fezolinetant | -3.94 (95% CI -5.71 to -2.16) | Data not separately specified in brief |
| Elinzanetant | -5.24 (95% CI -6.99 to -3.49) | -4.52 (95% CI -6.34 to -2.70) |
The research was conducted by Maria Julia Lemos of Kurah Women's Health Institute in Brazil and JoAnn E. Manson of Harvard Medical School. It was presented at the Menopause Society annual meeting and co-published in the journal Menopause. The study search covered PubMed, Embase, and Cochrane databases from inception to May 2026. All included trials had a low risk of bias.
How These Treatments Work
The medications target brain pathways involved in thermoregulation to reduce vasomotor symptoms that disrupt sleep. They are neurokinin (NK)-receptor antagonists. Fezolinetant, sold as Veozah, is an NK3 receptor antagonist. Elinzanetant, known as Lynkuet, is a dual NK1/NK3 receptor antagonist. They work on the brain's thermoregulation center to reduce hot flashes and night sweats.
Menopausal hormone therapy remains the preferred treatment for these symptoms. Some women, however, have medical contraindications or simply prefer non-hormonal options. Between 50 and 92 percent of women in menopause experience hot flushes and night sweats. Sleep problems affect 16 to 66 percent of women reporting menopause-related disruption.
Key Findings and Limitations
Early sleep benefits were observed within one month, which is significant as poor sleep is often the most bothersome vasomotor symptom. Five of the seven trials used the PROMIS SD-SF-8b questionnaire. This tool assesses sleep quality, restfulness, and difficulty falling or staying asleep over the past seven days. Two trials used different questionnaires and were analyzed separately.
Researchers noted several limitations. These include the relatively few trials available, reliance on patient-reported outcomes, and high heterogeneity in patient characteristics, regimens, and follow-up. The analysis could not isolate sleep benefits from broader vasomotor symptom relief. Head-to-head trials directly comparing fezolinetant and elinzanetant are still needed. Long-term data beyond 24 weeks is also limited.
More than one-third of women worldwide approaching or having reached menopause report depressive symptoms. The World Health Organization estimates more than one billion women will be living through menopause or postmenopause by 2030. Existing guidelines recommend systemic menopausal hormone therapy for women with hot flushes and related sleep problems, provided they have no medical contraindications.
Treatment should be discussed with a healthcare provider. This discussion must consider factors like age, time since menopause began, medical history, and risks of conditions including blood clots, stroke, and breast cancer. For suitable candidates, guidelines recommend considering hormone therapy before age 60 or within 10 years of natural menopause onset. Women who still have a uterus generally need estrogen combined with a progestogen to protect the womb lining.
Joint and muscle discomfort affects an estimated 65.4 percent of menopausal women. Vaginal dryness impacts about 44.8 percent of postmenopausal women. Symptom prevalence varies globally; hot flushes were reported by 65.9 percent of women in lower-income countries and 49.7 percent in high-income countries. The median age at menopause also varies, with one study in rural western Kenya finding it to be 48.3 years. Symptoms can significantly impact daily life, with a study of health workers in Kenya linking them to absenteeism and reduced workplace productivity.
For women exploring alternatives, the new meta-analysis provides evidence for discussing the suitability of non-hormonal NK-receptor antagonists with a healthcare provider.
