What is the new treatment for hot flashes? The rise of Neurokinin 3 (NK3) receptor antagonists
For decades, hormone replacement therapy (HRT) was the primary treatment for hot flashes. However, HRT isn't suitable for everyone, especially those with certain health risks. This led to the search for effective non-hormonal options. The most notable recent development is the approval of neurokinin 3 (NK3) receptor antagonists.
In May 2023, Veozah (fezolinetant) was approved by the FDA for treating moderate to severe hot flashes (vasomotor symptoms) caused by menopause. This was the first drug in its class approved for this use. Veozah works differently than hormone therapy, targeting a specific pathway in the brain that regulates temperature.
How Veozah works to control body temperature
Veozah targets the brain's temperature control center, the hypothalamus. In menopausal women, declining estrogen disrupts certain neurons (KNDy neurons), causing them to become overactive and trigger hot flashes. Fezolinetant blocks the NK3 receptor, preventing neurokinin B (NKB) from binding to it. This dampens the activity of the KNDy neurons, helping to restore the brain's temperature balance and reduce hot flashes. Clinical trials showed that Veozah could reduce the frequency and severity of hot flashes within a week for some patients, with significant reductions seen within 12 weeks.
Important considerations and precautions for Veozah
Veozah is a promising new option, but it carries a rare risk of serious liver injury. The FDA issued a Boxed Warning for this risk.
Liver monitoring is required for patients taking Veozah:
- A test before starting treatment.
- Monthly tests for the first three months.
- Additional tests at months 6 and 9.
If liver tests show concerning results, the medication may be stopped. Patients should report symptoms of liver problems, such as unusual fatigue or yellowing of skin/eyes, to their doctor immediately.
Common side effects include:
- Abdominal pain
- Diarrhea
- Insomnia
- Back pain
- Elevated liver transaminases
Comparison: Veozah vs. Other Hot Flash Treatments
To understand where Veozah fits in the treatment landscape, it's helpful to compare it to other options. While HRT remains the most effective, non-hormonal alternatives have varying levels of efficacy and different side effect profiles.
| Feature | Veozah (NK3 Antagonist) | Hormone Replacement Therapy (HRT) | SSRIs / SNRIs |
|---|---|---|---|
| Mechanism | Blocks neurokinin B (NKB) binding in the brain to restore thermoregulatory balance. | Replaces declining estrogen levels to reduce vasomotor symptoms. | Modulates serotonin and norepinephrine levels in the brain. |
| Efficacy | Highly effective, with significant reductions in frequency and severity shown in clinical trials. | Most effective treatment for hot flashes, typically offering a 75% reduction in frequency. | Modest to moderate relief, with a 24%-69% reduction reported in various studies. |
| Side Effects | Abdominal pain, diarrhea, insomnia, back pain; rare but serious risk of liver injury. | Can have side effects, including increased risk of breast cancer, blood clots, and cardiovascular disease for certain women. | Drowsiness, weight gain, nausea, decreased libido, and hypertension. |
| Hormonal? | No, it is a non-hormonal treatment. | Yes, contains hormones (estrogen and/or progestin). | No, it is a non-hormonal treatment. |
| Candidate For | Women with moderate to severe hot flashes, especially those who cannot take HRT. | Women without contraindications, typically under 60 and within 10 years of menopause. | Women with mild to moderate symptoms or those with co-occurring mood symptoms. |
The future of non-hormonal therapy: Elinzanetant
The development of non-hormonal options continues. Elinzanetant, which blocks both neurokinin-1 and neurokinin-3 receptors, has shown promise in trials. It may also help with menopause-related sleep issues. A New Drug Application for elinzanetant was submitted to the FDA, with a potential launch in 2025. These targeted therapies offer hope for more personalized treatments for menopausal symptoms.
Lifestyle and behavioral strategies
In addition to medication, lifestyle and behavioral changes can help manage hot flashes, either alone for mild symptoms or combined with medication for more severe cases.
- Cognitive Behavioral Therapy (CBT): Helps women manage the distress related to hot flashes.
- Clinical Hypnosis: Can reduce the frequency and severity of hot flashes.
- Dietary Adjustments: Avoiding triggers like spicy food, caffeine, hot drinks, and alcohol can help.
- Weight and Exercise: Maintaining a healthy weight and exercising regularly may improve symptoms.
Conclusion: A new era for menopause management
The approval of Veozah is a significant step in treating hot flashes, especially for women unable or unwilling to use hormonal treatments. This non-hormonal NK3 receptor antagonist targets the brain pathways responsible for temperature regulation during menopause. Despite the need for liver monitoring, Veozah is a highly effective option that can improve quality of life. With further non-hormonal options like elinzanetant in development, menopause management is moving towards more personalized and targeted approaches. Combining these medical advancements with behavioral and lifestyle strategies provides women with more comprehensive tools to manage menopause symptoms.
Outbound Link: For more details on the FDA's approval of Veozah, you can visit the official press release on the FDA website.
