A new alternative to hormones for managing menopausal hot flashes?

Dr Brigitte Raccah-Tebeka, gynecolo-endocrinologist, and Pr Geneviève Plu-Bureau, gynecologist and epidemiologist in Paris, both ambassadors for Agir pour le Cœur des Femmes, bring you the latest news on an alternative treatment to hormones for menopausal hot flushes.

Hot flushes and night sweats affect the daily lives and quality of life of many women during the menopause, sometimes beginning up to 80% a few years beforehand, according to the latest studies. The most effective treatment is hormonal menopause therapy, thanks to the estrogens it contains. Some women, however, do not wish to use hormones, and other patients cannot use hormone therapy because of their medical history. Contraindications to estrogens include cardiovascular events (such as myocardial infarction or ischemic stroke) and certain thromboembolic events.
Numerous alternatives, both medicinal (certain antidepressants, clonidine, pregabalin, etc.) and non-medicinal (acupuncture, yoga, behavioral therapy, etc.), have been tested, but their efficacy remains inferior to that of hormone therapy.
In recent years, the physiology of hot flushes has been better identified, involving specific neurons (kisspeptin/ neurokinin B/ dynorphin (KNDy)) in the hypothalamic thermoregulation center at the heart of the brain. These neurons are stimulated by the neuropeptide neurokinin B, which acts on neurokinin 3 receptors inhibited by estrogen. With the onset of menopause, estrogen decreases and activation of the neurokinin 3 receptor remains unchecked, leading to hypertrophy of the KNDy neurons, which in turn alters the thermoregulatory center and encourages flushing.
New molecules blocking these neurons have been developed with the aim of improving the management of flushing.
For example, fezolinetant was tested in post-menopausal women aged 40 to 65 with at least 7 moderate to severe flushes per day. Compared with placebo, this molecule significantly reduced hot flushes from the first week of treatment, over the 52 weeks of the study. Efficacy related to both the frequency and intensity of hot flushes. Side effects appeared to be infrequent, and did not lead to premature discontinuation of treatment.
The development of this new molecule has just received European marketing authorization, with commercialization scheduled for early 2025. It promises to offer a new therapeutic solution for menopausal women who are unwilling or unable to use hormonal menopause treatments.

For more information:
Johnson KA, Martin N, Nappi RE, Neal-Perry G, Shapiro M, Stute P, Thurston RC, Wolfman W, English M, Franklin C, Lee M, Santoro N. Efficacy and Safety of Fezolinetant in Moderate-to-Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocrinol Metab. 2023 Feb 3:dgad058. doi: 10.1210/clinem/dgad058. Epub ahead of print. PMID: 36734148.

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