More than 50 percent of all menopausal women experience hot flashes, which can persist for an average of seven years. Hot flashes affect more than half of all menopausal women and can last up to seven years on average. Hormone therapy, while effective and safe when administered properly, has some risk, and not all patients are suitable candidates or willing to pursue this treatment option. Fortunately, NK3R antagonists, a new class of non-hormonal medicines, have emerged as an effective alternative to hormone treatment.

Menopause and occurrence of hot flashes

Menopause is linked with a considerable symptomatic intensity, with about two-thirds of postmenopausal women experiencing vasomotor symptoms, hot flushes, and night sweats. A hot flush is defined as a subjective experience of high heat that is accompanied by objective indicators of cutaneous vasodilation and a subsequent decline in core temperature. The improper activation of heat dissipation effectors causes this thermoregulatory response to perceived warmth. It has been proposed that this altered thermoregulatory response results from sudden changes in hormone concentrations associated with human menopause, such as estrogen insufficiency.

Old methodology of hormone-therapy

Hormone replacement treatment has traditionally been used to assist restore hormonal balance and hence alleviate hot flushes. Hormone replacement treatment, on the other hand, may not be appropriate in women who have an elevated risk of cardiovascular disease, thromboembolic illness, or a higher likelihood of specific cancer types, such as breast and endometrial cancer. As a result, its efficiency is restricted by the duration of therapy prescribed and the presence of any contraindications that exclude its usage. Alternative treatments include selective serotonin reuptake inhibitors (SSRIs), gabapentin, cognitive behavioral therapy, herbal medicines, acupuncture, and dietary and lifestyle changes.

New alternative to hormone therapy

Estrogen replacement is often not indicated, hence alternate, effective therapeutic alternatives are necessary. NKB, a hypothalamic neuropeptide, has emerged as a major regulator of the “normal” female reproductive axis. NKB is a peptide of the tachykinin family that is encoded by the TAC3 gene in humans. NKB interacts to the neurokinin 3 receptor (NK3R), which would be encoded by TACR3. Individuals with homozygous impairment mutations in either TAC3 or TACR3 have been demonstrated to suffer phenotypical hypogonadotropic hypogonadism with failure of pubertal progression. Affected people also have signs of abnormal intrauterine and perinatal stimulation of the reproductive axis. This research implies that NKB/NK3R signaling is important in the neuroendocrine regulation of human reproduction. Because activation of the NKB/NK3R signaling pathway has been known to trigger hot flushes, antagonism of this signal transduction pathway naturally arises as a possible therapeutic target to help alleviate these symptoms. As stated, central inhibition of NKB signaling in the mPOA, can block the physiological hot flush response caused by kisspeptin neuron activation in the Arc. This may be applied to a human model, where neurokinin receptor antagonism reduces the hot flush response.

Conclusion and future prospects

The existing literature supports the argument that NK3R antagonism is a great target for prospective pharmacological investigations, with encouraging findings on hot flush frequency, severity, and effect reduction. The significance of these investigations go beyond menopause and may be a viable therapeutic option for individuals experiencing hot flushes as a result of estrogen deprivation therapy in breast cancer and androgen deprivation therapy in prostate cancer. Further prospective clinical trials will offer a stronger evidence foundation for targeting the NKB/NK3R signalling pathway in the treatment of hot flush symptoms. And there is the opportunity of targeting the NKB/NK3R signalling pathway in the treatment of dysfunctional sex hormone-dependent disorders, which has to be investigated further.