Menopausal Hot Flashes: A Concise Review Original paper

What was reviewed?

This comprehensive review article synthesizes current knowledge on menopausal hot flashes (HFs), focusing on epidemiology, pathophysiology, risk factors, and a stepwise approach to management. The review covers a spectrum of treatment options, including hormonal, nonhormonal, and alternative therapies, and highlights recent research on neuropeptides and genetic factors. Special emphasis is placed on the neuroendocrine mechanisms underlying HFs, such as the roles of estrogen deficiency, serotonin, norepinephrine, and the kisspeptin-neurokinin B-dynorphin (KNDy) neuronal system, alongside the potential involvement of calcitonin gene-related peptide (CGRP). The review integrates findings from epidemiological studies, clinical trials, and mechanistic research, providing clinicians with an updated framework for understanding and managing HFs.

Who was reviewed?

The article synthesizes findings from numerous population-based studies, meta-analyses, clinical trials, and basic science investigations involving peri- and postmenopausal women worldwide. The review draws on data from diverse geographic populations, including Indian, Turkish, Australian, European, North American, South American, and Asian cohorts, to frame the global prevalence and heterogeneity of HFs. Evidence is also incorporated from genetic association studies, neuroendocrine research in both human and animal models, and clinical trials assessing pharmacologic and nonpharmacologic treatments. Special consideration is given to subgroups such as women with breast cancer and those with specific contraindications to hormone replacement therapy.

Most important findings

Hot flashes affect approximately 85% of menopausal women, with duration and severity varying widely by geography, genetics, and lifestyle. Obesity, African descent, lower socioeconomic status, premenstrual syndrome, sedentary lifestyle, and smoking are consistently associated risk factors. Genetic variants, particularly in the tachykinin receptor 3 (NK3R) gene, have emerged as key contributors to vasomotor symptom susceptibility, offering potential targets for personalized therapy. The pathophysiology of HFs centers on hypothalamic thermoregulatory dysfunction, with estrogen deficiency, altered serotonin and norepinephrine signaling, and activation of the KNDy neuronal system (notably neurokinin B) all implicated. The review highlights the role of CGRP, a potent vasodilator, in mediating peripheral symptoms of HFs, underlining the complex neuropeptide interplay. Standard management prioritizes hormonal replacement therapy (HRT) for moderate-to-severe HFs, with selective serotonin and norepinephrine reuptake inhibitors (SSRIs/SNRIs) as effective nonhormonal alternatives. Gabapentin and other agents are reserved for specific scenarios or refractory cases. Novel therapies under investigation include neurokinin 3 receptor antagonists and stellate ganglion block. While alternative therapies (such as acupuncture and plant-based treatments) show promise in small studies, robust evidence remains limited.

Key implications

The review underscores the multifactorial, neuroendocrine basis of menopausal hot flashes, highlighting opportunities for targeted interventions beyond conventional HRT. The emerging roles of neuropeptides such as neurokinin B and CGRP, as well as genetic susceptibility loci, provide fertile ground for future research and development of individualized therapies. Clinicians are advised to adopt a stepwise, patient-centered approach to management, balancing symptom severity, comorbidities, and patient preferences. The integration of nonhormonal and alternative therapies may further expand treatment options, especially for women with contraindications to HRT. For microbiome researchers and clinicians, the article’s neuroendocrine focus suggests indirect but important avenues for exploring gut-brain axis and microbial modulation of neuropeptide pathways in menopausal symptomatology.