Fezolinetant is a new medication gaining attention for its effectiveness in managing moderate to severe vasomotor symptoms, commonly known as hot flashes and night sweats. Vasomotor symptoms are among the most distressing symptoms of menopause, and they are most likely the first thing women mention in my menopause consultation. They result from the body's response to decreased estrogen levels and can significantly impact the quality of life.
How does it work?
Fezolinetant acts in the hypothalamus, the part of your brain that regulates almost anything, including body temperature. It is sometimes referred to as the body’s thermostat, processing the signals from heat receptors and generating responses like warming the body by shivering or cooling it down by sweating.
In normal circumstances, oestrogen supports thermoregulation through mechanisms that help maintain a stable internal body temperature in response to environmental changes and metabolic demands. Specifically, it prevents the temperature-regulating centre from producing too much heat. Together with progesterone, it plays a crucial role in temperature changes throughout the menstrual cycle and is highly important for fertility.
During menopause, however, the sharp decline in oestrogen levels disrupts the standard feedback mechanisms in the hypothalamus, leading to an unstable thermoregulatory set point.
The temperature regulatory centre becomes more sensitive to small fluctuations in internal and external temperatures, resulting in hot flashes and night sweats.
Now, I have come to realise, something that is widely underestimated even in the scientific community: I believe that changes in hormone levels, rather than their static concentrations, play a critical role in physiological responses.
That is why the sudden drop in oestrogens is more impactful than the absolute low levels of estrogen that follow during menopause.
This, at least, partially explains why men have no vasomotor symptoms while having deficient oestrogen levels. This is why women, after surgical menopause, often experience more severe symptoms. And why symptoms reappear after stopping Hormone Replacement Therapy (HRT), supporting a slow weaning off. This is why menopausal symptoms usually diminish over time.
So, how does Fezolinetant work? It blocks neurokinin B, a peptide involved in the temperature-regulating process that happens in the hypothalamus. It stops the overreaction to minor fluctuations and reduces hot flash frequency and severity.
How much?
Fezolinetant is typically taken orally, one tablet of 45 mg per day. It should be taken at the same time of the day to maintain consistent blood levels.
Adverse reactions?
Side effects such as nausea, headache, and fatigue are not common. If they occur, they are generally mild to moderate and often decrease as the body adjusts to the medication. No difference was found compared to the placebo group.
When NOT to take
If you have a known allergy to Fezolinetant or its components, you may have to try it first to determine whether you have an allergy.
Also, do not take it if you have severe kidney disease or severe liver impairment.
Fezolinetant should be avoided if you have severe uncontrolled hypertension, a history of myocardial infarction, severe coronary artery disease, unstable angina, severe heart failure, and certain arrhythmias due to the potential risks of getting worse. These patients require careful cardiovascular management, and a healthcare provider should thoroughly evaluate the introduction of new medications to ensure safety and efficacy.
According to the latest available research, the precautionary approach to prescribing Fezolinetant in patients with certain cardiovascular conditions is primarily based on general clinical considerations rather than direct evidence from studies linking Fezolinetant to adverse cardiovascular outcomes.
Interactions with other medications
Fezolinetant can interact with other medications, potentially altering their effects.
Some antibiotics (f.e. Ciprofloxacin) and antidepressants (f.e. Fluvoxamine and
Duloxetine) increase Fezolinetant levels in the blood, raising the risk of side effects.
Some antiepileptic drugs (f.e. Carbamazepine and Phenobarbital), as well as smoking, decrease Fezolinetant levels, reducing its effectiveness.
Hormone replacement therapy (HRT) should be closely monitored when used together.
Always inform your healthcare provider about your current medications and supplements to avoid potential interactions.
A note on Fezolinetant and breast cancer
Current evidence suggests that Fezolinetant does not increase the risk of breast cancer, making it a safe option for women concerned about this risk. However, long-term studies are still needed to understand its safety profile fully. Women with a history of breast cancer or those at high risk should discuss all treatment options with an expert on menopause treatment.
The statement given by the drug company on treating women with a history of breast cancer says: Because Fezolinetant was not studied in patients with breast cancer experiencing menopause-like symptoms and only studied in menopausal women, future research should be conducted to evaluate the safety and efficacy.
A note on that from an expert.
It's a real shame that the women who need it most, the women who have had breast cancer and tend to have more severe symptoms during their treatment, are being made insecure.
The statement given by the company does not mean that fezolinetant cannot be prescribed in these cases, as it is not contraindicated. However, these women need to be made aware that it has not been studied enough and that they are being left to accept a risk, albeit probably an extremely small one, to achieve a significantly better quality of life.
Conclusion
Fezolinetant is a promising option for managing vasomotor symptoms associated with menopause, offering a non-hormonal alternative.
Keep in mind it only treats a symptom, which I do agree is very important, and it seems to do this very well, but doesn’t change the total impact of menopausal oestrogen deficiency.
It is a fascinating new drug, and I look forward to seeing what long-term experience shows.
Dr. Paul Raas
9 June 2024
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