Does fezolinetant have an effect on sleep?

• Sleep disturbances are associated with VMS and frequent awakenings during the night due to night sweats.^6,7 Disturbed sleep increases with increasing VMS frequency and severity.⁸ 
• Fezolinetant has been found to improve sleep disturbances by addressing the underlying cause of VMS and night sweats, without inducing sleep.^5,9,10 .
• Patient-reported outcome (PRO) measures of sleep disturbance / impairment measured in trials of fezolinetant included:
  • PRO Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b): assesses sleep disturbance over the previous seven days and includes perceptions of restless sleep, satisfaction with sleep, refreshing sleep, difficulties sleeping, getting to sleep or staying asleep, amount of sleep, and sleep quality.⁷
  • PROMIS Sleep-Related Impairment - Short Form 8a (PROMIS SRI SF 8a): assesses the impact of sleep impairments over the previous seven days.⁵
  • Patient Global Impression of Change - Sleep Disturbance (PGIC SD): assesses how well participants were sleeping at that time compared with the start of the study.^9,10
  • Patient Global Impression of Severity - Sleep Disturbance (PGI-S SD): assesses the severity of any current problems while sleeping at night.^9,10
• Higher scores on each measure indicate more sleep disturbance / impairment.
• Disturbed sleep was not a prerequisite for study inclusion.^9–11

OPTION-VMS real-world, Phase 4 study preliminary results^1,2 

• In the second preliminary analysis, women prescribed fezolinetant (n = 375) demonstrated statistically significant within-group improvement in VMS bother, as measured by the MENQOL VMS domain, at Week 12 (primary outcome) and at Weeks 4 and 8 (secondary outcomes) (p < 0.001 for all).
• Fezolinetant treatment was associated with statistically significant within-group improvements in both objective actigraphy sleep (wakefulness after sleep onset [WASO], sleep efficiency, and sleep latency) endpoints (p < 0.05) and subjective sleep (PROMIS SD SF 8b total T-scores) endpoints (p < 0.001).

Figure 1. Actigraphy sleep endpoints: adjusted LS mean change (95% CI) from Baseline²

Figure 2. PROMIS SD SF 8b total T-score (fezolinetant treatment): adjusted LS mean change from Baseline²

• Although treatment types were not compared, SSRIs/SNRIs and other non-HT groups also had statistically significant within-group improvements compared to baseline in the MENQOL VMS domain and PROMIS SD SF 8b total T-scores.
• Actigraphy sleep endpoints did not show statistical significance in the SSRIs/SNRIs group; statistically significant within-group improvements in only WASO were observed in the other non-HT group (e.g., gabapentin).

Australian real-world study, ADELE-AU, preliminary results

• Improvement in sleep disturbance, via the PGI-C SD at Week 12, the primary endpoint, was associated with fezolinetant with 68.2% of participants reporting being “moderately better” or “much better”.³
• Change in sleep disturbance, PROMIS SD SF 8b, improved from baseline to Weeks 4, 8, and 12 (p < 0.001 for all).³

Figure 3. Women reporting “moderately better” or “much better” improvement in PGI-C SD at Weeks 4, 8, and 12 ³

Adapted from: Rodrigo N, Rayment E, Jang C, et al. AMS 2026.

Figure 4. Change in sleep disturbance (PROMIS SD SF 8b) at Weeks 4, 8, and 12 ³

Pooled SKYLIGHT 1 and 2 post-hoc analysis⁴

• Fezolinetant 30 mg and 45 mg improved sleep disturbance versus placebo at 12 weeks, regardless of baseline sleep status.
• At weeks 12 and 52, both doses showed correlations between VMS frequency/severity sleep disturbance.

SKYLIGHT 1 and 2 Phase 3 individual trial results

• In SKYLIGHT 1, improvements in patient-reported sleep disturbance in fezolinetant-treated participants were observed but generally did not reach statistical significance.⁹ 
• In SKYLIGHT 2, fezolinetant 45 mg significantly reduced PROMIS SD SF 8b total score from Baseline to Weeks 4 and 12 (p ≤ 0.01).¹⁰ 

Figure 5. Change in PROMIS SD SF 8b total score from Baseline to Weeks 4 and 12 in SKYLIGHT 1 and SKYLIGHT 2^9,10

Adapted from: Lederman S, Lancet 2023 and Johnson KA, J Clin Endocrinol Metab. 2023

1. Pozlep B. OPTION-VMS: First real-world fezolinetant effectiveness and safety data, including objective sleep data, in a phase 4 observational study of non-hormonal treatments for bothersome menopause-associated vasomotor symptoms [oral slide presentation]. Congress of Slovenian Gynaecologists and Obstetricians (SGC). Ljubljana, Slovenia. 2026.

2. Shapiro M, Maki PM, Larkin L, et al. Fezolinetant and real-world sleep outcomes in the phase 4 OPTION-VMS study: second preliminary analysis of patient-reported and actigraphy-derived endpoints [oral slide presentation]. International Menopause Society (IMS) 20th World Congress on Menopause. Rio de Janeiro, Brazil. 2026.

3. Rodrigo N, Rayment E, Jang C, et al. A real-world study describing sleep outcomes among women using fezolinetant in Australia (ADELE-AU): preliminary analysis [oral slide presentation]. Australasian Menopause Society (AMS) Annual Congress 2026. Sydney, AU. 2026.

4. Cano A, Perry GN, Martins K, et al. Effect of fezolinetant on sleep, health-related quality of life and work productivity. Climacteric. 2026;ahead-of-print(ahead-of-print):1-8. Available at: https://doi.org/10.1080/13697137.2026.2715238.

5. C.M. MS, Cano A, Nappi RE, et al. Effect of fezolinetant on sleep disturbance and impairment during treatment of vasomotor symptoms due to menopause. Maturitas. 2024;186107999. Available at: https://doi.org/10.1016/j.maturitas.2024.107999.

6. Thurston RC, Chang Y, Buysse DJ, et al. Hot flashes and awakenings among midlife women. SLEEP. 2019;42(9):zsz131. Available at: https://doi.org/10.1093/sleep/zsz131.

7. English M, Stoykova B, Slota C, et al. Qualitative study: burden of menopause-associated vasomotor symptoms (VMS) and validation of PROMIS Sleep Disturbance and Sleep-Related Impairment measures for assessment of VMS impact on sleep. J. Patient-Rep. Outcomes. 2021;5(1):37. Available at: https://doi.org/10.1186/s41687-021-00289-y.

8. DePree B, Shiozawa A, King D, et al. Association of menopausal vasomotor symptom severity with sleep and work impairments: a US survey. Menopause. 2023;30(9):887-897. Available at: https://doi.org/10.1097/gme.0000000000002237.

9. Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401(10382):1091-1102. Available at: https://doi.org/10.1016/s0140-6736(23)00085-5.

10. Johnson KA, Martin N, Nappi RE, et al. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J. Clin. Endocrinol. Metab. 2023;108(8):1981-1997. Available at: https://doi.org/10.1210/clinem/dgad058.

11. Schaudig K, Wang X, Bouchard C, et al. Efficacy and safety of fezolinetant for moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy: phase 3b randomised controlled trial. BMJ. 2024;387(387):e079525. Available at: https://doi.org/10.1136/bmj-2024-079525.