Menopausal symptom management: Fezolinetant's varied doses provide effective relief for vasomotor symptoms in women - A metaanalysis of 3291 participant

Amal M. Elhusein, Hammad A. Fadlalmola, Huda H. Abedelwahed, Alawìa A. Elshaikh, Amel E. Banaga, Manal H.F. Alrahman, Nafesa H. Abdelgadim, Insaf H. Mohammed, Afaf A.A. Abdalla, Fatma A.M. Abdalla, Ebtihag M. Abd Allah, Nagwa I. Abbas, Abdullah D. Alhujaili, Egbal A. Almkiy, Eltayeb A. Idress, Eltayeb M. Awadalkareem, Selwa Y. Abdeldafie, Prema Balusamy, Rasha A. Mohamed, Rami S.M. Aloufi, Mohammed Habiballa, Mohammed A. Abdelmalik, Mohammed M. Alhejaili, Ibrahim A. Ibrahim, Huda K. Masaad


Menopause represents the physiological transition when a woman's reproductive period ends associated with a variety of symptoms, including vasomotor symptoms, such as night sweats and hot flashes. This systematic review and meta-analysis aimed to assess the effectiveness and safety of oral Fezolinetant for treating vasomotor symptoms associated with menopause. Five electronic databases were searched from their inception until May 2023. Via the Cochrane risk of bias tool, two reviewers assessed the studies' quality. The primary outcomes were a decrease in VMSs frequency and severity and safety outcomes at 4 and 12 weeks. Data were extracted and then analyzed using RevMan software. This meta-analysis included six trials with a total of 3291 women that compared Fezolinetant to a placebo in the treatment of menopausal VMSs. After 4 and 12 weeks of therapy, fezolinetant at 30 mg QD or 45 mg QD substantially decreased the frequency and severity of VMSs per 24 hours compared to placebo. Fezolinetant at 90 mg BID, 30 mg QD, or 45 mg QD did not show a significant difference in the rate of treatment-emergent adverse events (TEAEs), headache, and TEAEs leading to permanent discontinuation compared to placebo. Fezolinetant proves to be a successful and well-tolerated remedy for menopausal women suffering from VMSs. Notably, the 45 mg daily dosage over 12 weeks exhibited significant efficacy. Nonetheless, extensive future trials are necessary to ascertain its long-term safety, effectiveness, and relative potency compared to alternative VMS treatments like hormone therapy. (Afr J Reprod Health 2024; 28 [3]: 99-113)

Full Text:



McCarthy M and Raval AP. The peri-menopause in a

woman’s life: a systemic inflammatory phase that

enables later neurodegenerative disease. Vol. 17,

Journal of Neuroinflammation. BioMed Central Ltd;

Pachman DR, Jones JM and Loprinzi CL. Management of

menopause-associated vasomotor symptoms: Current

treatment options, challenges and future directions

[Internet]. International Journal of Women’s Health.

Available from:

Blümel JE, Chedraui P, Barón, G, Belzares E, Bencosme A,

Calle A, Danckers L, Espinoza MT, Flores D, Gómez

G, Hernández-Bueno JA, Izaguirre H, León-León P,

Lima S, Mezones‐Holguín E, Monterrosa Á, Mostajo

D, Navarro D, Ojeda E, Onatra W, Royer M, Soto E,

Tserotas K and Vallejo S. A large multinational study

of vasomotor symptom prevalence, duration, and

impact on quality of life in middle-aged women.

Menopause, 2011a; 18:778–785.

Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA,

Powell L, Sternfeld B and Matthews K. Longitudinal

analysis of the association between vasomotor

symptoms and race/ethnicity across the menopausal

transition: study of women's health across the nation.

Am J Public Health. 2006 Jul;96(7):1226-35. doi:

2105/AJPH.2005.066936. Epub 2006 May 30.

PMID: 16735636; PMCID: PMC1483882.

Woods NF and Mitchell ES. Symptoms during the

perimenopause: prevalence, severity, trajectory, and

significance in women’s lives. Am J Med. 2005


Umland EM and Falconieri L. Treatment options for

vasomotor symptoms in menopause: Focus on

desvenlafaxine. Vol. 4, International Journal of

Women’s Health. Dove Medical Press Ltd; 2012. p.


Mehta J, Kling JM and Manson JAE. Risks, Benefits, and

Treatment Modalities of Menopausal Hormone

Therapy: Current Concepts. Vol. 12, Frontiers in

Endocrinology. Frontiers Media S.A.; 2021.

Khan SJ, Kapoor E, Faubion SS, Kling JM. Vasomotor

Symptoms During Menopause: A Practical Guide on

Current Treatments and Future Perspectives. Vol. 15,

International Journal of Women’s Health. Dove

Medical Press Ltd; 2023. p. 273–87.

Azizi M, Khani S, Kamali M and Elyasi F. The Efficacy and

Safety of Selective Serotonin Reuptake Inhibitors and

Serotonin-Norepinephrine Reuptake Inhibitors in the

Treatment of Menopausal Hot Flashes: A Systematic

Review of Clinical Trials. Vol. 47, Iranian Journal of

Medical Sciences. Shiraz University of Medical

Sciences; 2022. p. 173–93.

Stubbs C, Mattingly L, Crawford SA, Wickersham EA,

Brockhaus JL and Mccarthy LH. Do SSRIs and SNRIs

reduce the frequency and/or severity of hot flashes in

menopausal women HHS Public Access Summary of

the Issues. Vol. 110, J Okla State Med Assoc. 2017.

Koysombat K, McGown P, Nyunt S, Abbara A and Dhillo

WS. New advances in menopause symptom

management. Best Pract Res Clin Endocrinol Metab.


Depypere H, Lademacher C, Siddiqui E and Fraser GL.

Fezolinetant in the treatment of vasomotor symptoms

associated with menopause. Expert Opin Investig

Drugs. 2021 Jul 3;30(7):681–94.

Press Release Astellas Provides Update on Fezolinetant New

Drug Application in U.S [Internet]. Available from:

Tahara A, Takamatsu H, Ohtake A, Tanaka-Amino K and

Kaku S. Effects of neurokinin 3 receptor antagonist

fezolinetant on hot flash-like symptoms in

ovariectomized rats. Eur J Pharmacol. 2021


Modi M and Dhillo WS. Neurokinin 3 Receptor

Antagonism: A Novel Treatment for Menopausal Hot

Flushes. Neuroendocrinology. 2019;109(3):242–8.

Drewe J, Bucher KA and Zahner C. A systematic review of

non-hormonal treatments of vasomotor symptoms in

climacteric and cancer patients. Springerplus.


Sahni S, Lobo-Romero A and Smith T. Contemporary Nonhormonal Therapies for the Management of Vasomotor

Symptoms Associated with Menopause: A Literature

Review. Eur Endocrinol. 2021;17(2):133.

Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M,

Stute P, Thurston RC, English M, Franklin C, Lee M

and Neal-Perry G. Fezolinetant for treatment of

moderate-to-severe vasomotor symptoms associated

with menopause (SKYLIGHT 1): a phase 3 randomised

controlled study. Lancet. 2023 Apr

;401(10382):1091-1102. doi: 10.1016/S0140-

(23)00085-5. Epub 2023 Mar 13. PMID:

Fraser GL, Lederman S, Waldbaum A, Kroll R, Santoro N,

Lee M, Skillern L and Ramael S. A phase 2b,randomized, placebo-controlled, double-blind, doseranging study of the neurokinin 3 receptor antagonist

fezolinetant for vasomotor symptoms associated with

menopause. Menopause. 2020 Apr;27(4):382-392. doi:

1097/GME.0000000000001510. PMID: 32102086;

PMCID: PMC7147405.

Cumpston M, Li T, Page MJ, Chandler J, Welch VA,

Higgins JP and Thomas J. Updated guidance for trusted

systematic reviews: a new edition of the Cochrane

Handbook for Systematic Reviews of Interventions.

Cochrane Database Syst Rev. 2019 Oct

;10(10):ED000142. doi:

1002/14651858.ED000142. PMID: 31643080;

PMCID: PMC10284251.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC,

Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J and

Moher D. The PRISMA statement for reporting

systematic reviews and meta-analyses of studies that

evaluate health care interventions: explanation and

elaboration. J Clin Epidemiol. 2009 Oct;62(10):e1-34.

doi: 10.1016/j.jclinepi.2009.06.006. Epub 2009 Jul 23.

PMID: 19631507.

Radtke J V., Terhorst L and Cohen SM. The MenopauseSpecific Quality of Life Questionnaire. Menopause.


Sterne JAC, Savović J, Page MJ and Elbers RG, Blencowe

NS, Boutron I, Cates CJ, Cheng HY, Corbett MS,

Eldridge SM, Emberson JR, Hernán MA, Hopewell S,

Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ,

Lasserson T, Li T, McAleenan A, Reeves BC,

Shepperd S, Shrier I, Stewart LA, Tilling K, White IR,

Whiting PF and Higgins JPT. RoB 2: a revised tool for

assessing risk of bias in randomised trials. BMJ. 2019

Aug 28;366:l4898. doi: 10.1136/bmj.l4898. PMID:

Neal-Perry G, Cano A, Lederman S, Nappi RE, Santoro N,

Wolfman W, English M, Franklin C, Valluri U and

Ottery FD. Safety of Fezolinetant for Vasomotor

Symptoms Associated With Menopause: A

Randomized Controlled Trial. Obstet Gynecol. 2023

Apr 1;141(4):737-747. doi:

1097/AOG.0000000000005114. Epub 2023 Mar 9.

PMID: 36897180; PMCID: PMC10026946.

Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M,

Stute P, Thurston RC, English M, Franklin C, Lee M

and Neal-Perry G. Fezolinetant for treatment of

moderate-to-severe vasomotor symptoms associated

with menopause (SKYLIGHT 1): a phase 3 randomized

controlled study. Lancet. 2023 Apr

;401(10382):1091-1102. doi: 10.1016/S0140-

(23)00085-5. Epub 2023 Mar 13. PMID:

Johnson KA, Martin N, Nappi RE, Neal-Perry G, Shapiro M,

Stute P, Thurston RC, Wolfman W, English M,

Franklin C, Lee M and Santoro N. Efficacy and Safety

of Fezolinetant in Moderate to Severe Vasomotor

Symptoms Associated with Menopause: A Phase 3

RCT. J Clin Endocrinol Metab. 2023 Jul

;108(8):1981-1997. doi: 10.1210/clinem/dgad058.

PMID: 36734148; PMCID: PMC10348473.

Depypere H, Timmerman D, Donders G, Sieprath P, Ramael

S, Combalbert J, Hoveyda HR and Fraser GL.

Treatment of Menopausal Vasomotor Symptoms with

Fezolinetant, a Neurokinin 3 Receptor Antagonist: A

Phase 2a Trial. J Clin Endocrinol Metab. 2019 Dec

;104(12):5893-5905. doi: 10.1210/jc.2019-00677.

PMID: 31415087.

Prague JK, Abbara A, Comninos AN, Jayasena CN, Higham

CE, Adaway J, Keevil BG, Veldhuis JD and Dhillo WS.

Neurokinin 3 Receptor Antagonists Do Not Increase

FSH or Estradiol Secretion in Menopausal Women. J

Endocr Soc. 2019 Nov 14;4(2):bvz009. doi:

1210/jendso/bvz009. PMID: 32318647; PMCID:


Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena

CN, Nash Z, Doyle C, Papadopoulou DA, Bloom SR,

Mohideen P, Panay N, Hunter MS, Veldhuis JD,

Webber LC, Huson L and Dhillo WS. Neurokinin 3

receptor antagonism as a novel treatment for

menopausal hot flushes: a phase 2, randomized, doubleblind, placebo-controlled trial. Lancet. 2017 May

;389(10081):1809-1820. doi: 10.1016/S0140-

(17)30823-1. Epub 2017 Apr 3. PMID: 28385352;

PMCID: PMC5439024.

Skorupskaite K and Anderson RA. Hypothalamic neurokinin

signalling and its application in reproductive medicine.

Pharmacol Ther. 2022 Feb;230:107960.

McCarthy MA, Dischino D, Maguire C, Leon S, Talbi R,

Cheung E, Schteingart CD, Rivière PJM, Reed SD,

Steiner RA and Victor M Navarro. Inhibiting Kiss1

Neurons With Kappa Opioid Receptor Agonists to

Treat Polycystic Ovary Syndrome and Vasomotor

Symptoms. J Clin Endocrinol Metab. 2022 Jan


Menown SJ and Tello JA. Neurokinin 3 Receptor

Antagonists Compared With Serotonin Norepinephrine

Reuptake Inhibitors for Non-Hormonal Treatment of

Menopausal Hot Flushes: A Systematic Qualitative

Review. Adv Ther. 2021 Oct 12;38(10):5025–45.

Modi M and Dhillo WS. Neurokinin 3 Receptor

Antagonism: A Novel Treatment for Menopausal Hot

Flushes. Neuroendocrinology. 2019;109(3):242–8.

Fournier A, Mesrine S, Dossus L, Boutron-Ruault MC,

Clavel-Chapelon F and Chabbert-Buffet N. Risk of

breast cancer after stopping menopausal hormone

therapy in the E3N cohort. Breast Cancer Res Treat.

Jun 30;145(2):535–43.

Shams T, Firwana B, Habib F, Alshahrani A, AlNouh B,

Murad MH and Ferwana M. "SSRIs for hot flashes: a

systematic review and meta-analysis of randomized

trials." Journal of general internal medicine 29 (2014):


Higgins A. Antidepressant-associated sexual dysfunction:

impact, effects, and treatment. Drug Healthc Patient

Saf. 2010 Sep;141.


  • There are currently no refbacks.