Nonhormonal therapies transform menopause care in 2025

There was a pivotal shift in menopause care in 2025, marked by significant advances in non-hormonal treatments for vasomotor symptoms (VMS), particularly hot flashes.

Central to this progress was the FDA approval of elinzanetant in October 2025, a dual neurokinin receptor antagonist that targets KNDy neurons in the hypothalamus. By interrupting the neural pathway responsible for thermoregulation, elinzanetant reduces hot flash frequency without the safety concerns associated with estrogen-based therapies. In addition to alleviating VMS, the drug may also improve sleep and mood, broadening its potential benefits for postmenopausal women.

Elinzanetant follows the 2023 approval of fezolinetant, the first medication in the neurokinin receptor antagonist class. Together, these therapies represent the first targeted, non-hormonal treatments specifically designed to address the underlying mechanism of hot flashes.

Unlike estrogen, which acts broadly throughout the body, these agents work directly on the brain pathways driving symptoms. This distinction is especially important for women who cannot use hormone therapy because of a history of hormonally sensitive cancers, thromboembolic risk, or other contraindications.

The timing of these approvals also coincides with a major regulatory shift: in 2025, the FDA revised long-standing safety warnings on menopausal hormone therapy. These warnings, originally based on older studies involving higher-risk populations and outdated formulations, had emphasized risks such as cardiovascular disease, breast cancer, and dementia. Their removal reflects a more nuanced understanding of hormone therapy safety and has helped reframe discussions around menopause treatment options.

Clinical trial data underscore the effectiveness of neurokinin antagonists. Fezolinetant demonstrated nearly a 60% reduction in hot flash frequency across diverse populations. Elinzanetant’s phase 3 OASIS trials showed even greater efficacy, with a 74% reduction in moderate to severe VMS by week 12, along with meaningful improvements in sleep and a low rate of serious adverse events.

Differences in side effect profiles may guide individualized treatment decisions. For example, elinzanetant’s tendency to promote sleep may benefit women with prominent insomnia, while fezolinetant does not share this effect.

Looking ahead, research continues to expand the therapeutic landscape. Cendifensine, currently in phase 2 trials, represents a novel approach by acting on the monoamine system—serotonin, norepinephrine, and dopamine—while also modulating KNDy activity. Early results show reductions in hot flash frequency exceeding 80% within weeks, with potential additional benefits for mood and appetite.

Collectively, these developments signal a transformative era in menopause care, offering women effective, targeted, non-hormonal options after decades of limited innovation.

No relevant disclosures.

References

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