How does Veozah (estrogen or selective estrogen receptor modulators (SERMs)) treat vasomotor symptoms?

Veozah (Fezolinetant) for Vasomotor Symptoms Treatment

Veozah (fezolinetant) treats vasomotor symptoms of menopause through a novel non-hormonal mechanism as a neurokinin 3 (NK3) receptor antagonist that targets the disrupted thermoregulation underlying hot flashes and night sweats. Unlike estrogen or SERMs, Veozah works by modulating neural activity within the thermoregulatory center by crossing the blood-brain barrier, providing relief from vasomotor symptoms without hormonal effects. 1

Mechanism of Action

• Veozah functions as a neurokinin 3 receptor antagonist that targets the root cause of vasomotor symptoms by addressing disrupted thermoregulation 1
• It crosses the blood-brain barrier to modulate neural activity in the thermoregulatory center, providing direct relief from hot flashes and night sweats 1
• Unlike traditional hormone therapy which replaces estrogen, Veozah offers a non-hormonal approach for women who cannot or prefer not to use hormonal treatments 2

Efficacy and Clinical Evidence

• Clinical trials (SKYLIGHT 1™, SKYLIGHT 2™, and SKYLIGHT 4™) have established Veozah's efficacy and safety profile for moderate to severe vasomotor symptoms 1
• The recommended dosage is one 45 mg tablet daily, which demonstrates proportional pharmacokinetics with generally mild side effects 1
• Veozah represents a significant advancement as the first FDA-approved non-hormonal treatment specifically designed for vasomotor symptoms 2

Comparison with Traditional Treatments

• Hormone therapy with estrogen remains the most effective treatment for vasomotor symptoms, reducing frequency by approximately 75%, but carries risks including stroke, venous thromboembolism, and breast cancer (with combined therapy) 3
• SERMs like raloxifene and bazedoxifene prevent postmenopausal osteoporosis but have not been associated with reductions in vasomotor symptoms 4
• Other non-hormonal approaches like SSRIs/SNRIs (citalopram, desvenlafaxine, escitalopram, paroxetine, venlafaxine) and gabapentin reduce vasomotor symptoms by approximately 40-65% 3

Clinical Considerations and Caveats

• Veozah offers an important alternative for women who cannot take estrogen due to contraindications or personal preference 2
• Regular monitoring is recommended during Veozah treatment due to potential side effects, though these are generally mild 1
• Veozah's oral availability makes it a convenient and accessible option for women seeking relief from vasomotor symptoms 1
• Unlike hormone therapy which has multiple effects throughout the body, Veozah specifically targets the neurological pathway involved in hot flashes 1

Treatment Algorithm for Vasomotor Symptoms

1. First-line therapy for most women with bothersome vasomotor symptoms remains hormonal therapy with estrogen (with or without progestogen) 3
2. For women who cannot take estrogen or prefer non-hormonal options, Veozah represents a specific targeted therapy for vasomotor symptoms 2
3. Other non-hormonal options include SSRIs/SNRIs and gabapentin, which have moderate efficacy but different side effect profiles 5
4. Non-pharmacologic approaches like cognitive behavioral therapy may help reduce the perceived burden of hot flashes 5
5. Lifestyle modifications (weight loss if overweight, smoking cessation, limiting alcohol if it triggers symptoms) may provide additional benefit 5

Veozah represents an important advancement in treating vasomotor symptoms through a mechanism that directly targets the neurological pathway involved in thermoregulation rather than replacing hormones or modulating estrogen receptors.