Research · PMID 40253593
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
A profile of safety and efficacy of fezolinetant for the treatment of menopausal vasomotor symptoms.
Expert review of clinical pharmacology · May 2025 · Laura Cucinella, Chiara Cassani, Sara Tedeschi, Stefano Memoli, Ellis Martini, et al.
What this study found
INTRODUCTION: Fezolinetant is a first-in-class non-hormonal pharmacological treatment recently approved for moderate-to-severe vasomotor symptoms (VMS) associated with menopause. Its mechanism of action selectively targets the pathophysiology of VMS at hypothalamic level, antagonizing binding of neurokinin B, overexpressed in estrogen deprived menopausal women, to the neurokinin 3 receptor (NK3R) in the thermoregulatory center.
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Primary study
Is fezolinetant effective for menopausal hot flashes?
Fezolinetant, a neurokinin-3 receptor antagonist, reduced moderate-to-severe vasomotor symptoms in randomized trials of postmenopausal women. It offers a non-hormonal option when estrogen is contraindicated or declined.
Open evidence analysisSupporting literature
What therapies are most effective for vasomotor symptoms in perimenopause?
Systemic hormone therapy remains the most effective treatment for moderate-to-severe vasomotor symptoms across the menopause transition. When estrogen is declined or contraindicated, evidence-supported non-hormonal options—including fezolinetant and selected SSRIs/SNRIs—reduce symptoms, though with generally smaller effect than estrogen.
Open evidence analysisSupporting literature
Does hormone therapy improve sleep disturbance in menopause?
Menopausal hormone therapy can improve sleep when vasomotor symptoms are a major driver of disruption. Benefits for primary insomnia without hot flashes are less consistent across trials.
Open evidence analysisSupporting literature
Does hormone therapy help depression or anxiety during perimenopause?
Some trials suggest estrogen-based therapy may help depressive symptoms during the menopause transition, particularly when vasomotor symptoms coexist. It is not a substitute for standard treatment of major depressive disorder.
Open evidence analysisSupporting literature
Is menopause associated with cognitive changes or brain fog?
Many women report subjective cognitive difficulty during perimenopause, often linked to sleep disruption and vasomotor symptoms. Objective cognitive testing shows subtle changes in some cohorts, but HRT is not established as a treatment for brain fog alone.
Open evidence analysisSupporting literature
Does menopause cause weight gain and can hormone therapy help?
Menopause is associated with central adiposity and lean mass loss independent of aging alone. Hormone therapy is not a weight-loss treatment but may attenuate some menopause-related body composition shifts in selected women.
Open evidence analysis