Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause.

Menopause (New York, N.Y.) · January 2024 · Antonia Morga, Mayank Ajmera, Emily Gao, Oscar Patterson-Lomba, Angela Zhao, et al.

What this study found

The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS.

Open on PubMed DOI

systematic_review

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.

Core study

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 analysis

Core 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 analysis

Supporting literature

Does hormone therapy prevent cognitive decline or dementia?

WHI and subsequent analyses do not support HRT for dementia prevention when initiated in older postmenopausal women. Early-initiation cognitive studies are mixed and do not establish routine neuroprotection.

Open evidence analysis

Supporting 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 analysis

Supporting literature

How long should menopausal hormone therapy be continued?

Duration should be individualized based on symptom control, indication, and evolving risks. Many guidelines support continued use with annual reassessment rather than arbitrary stopping ages when benefits outweigh risks for that patient.

Open evidence analysis

Supporting 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 analysis

Supporting 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 analysis

Supporting 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

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