What’s in a name: are menopausal ‘hot flashes’ a symptom of menopause or a manifestation of neurovascular dysregulation? Original paper

What was reviewed?

This narrative review critically examines the conventional framing of hot flashes and night sweats, collectively termed vasomotor symptoms (VMS), as mere symptoms of menopause. The authors argue for a paradigm shift, proposing that these phenomena are better understood as manifestations of underlying autonomic neurovascular dysregulation. The review synthesizes epidemiological, genetic, and mechanistic evidence to explore the etiological complexity of VMS, emphasizing associations with neurological (sleep, mood, cognition) and cardiovascular conditions. Drawing on large-scale longitudinal studies from Australia, the UK, and the US, the authors identify four consistent patterns of vasomotor disturbances and discuss their possible biological and genetic bases, independent of cultural or socioeconomic factors. The review also addresses the limitations of current research, including the lack of objective monitoring tools and standard terminology, and highlights emerging insights from genetic studies and neurobiological pathways (notably the hypothalamic KNDy neurons and neurokinin B signaling). The authors call for robust mechanistic research and advocate for the reclassification of VMS to better inform clinical practice and research strategies.

Who was reviewed?

The review considers data from diverse populations of women undergoing the menopausal transition, as reported in prominent longitudinal cohort studies such as the Australian Longitudinal Study of Women’s Health (ALSWH), the 1946 British birth cohort, and the Study of Women Across the Nation (SWAN, USA). These cohorts encompass women from multiple geographic, cultural, and socioeconomic backgrounds, allowing the review to draw generalizable conclusions about the universality of VMS patterns. The reviewed studies include women experiencing natural or surgical menopause (e.g., following bilateral oophorectomy), and incorporate genetic sub-studies examining variants related to estrogen metabolism, estrogen receptors, and neurotransmitter pathways. The focus is on midlife and older women, typically in the peri- and postmenopausal stages, and the analysis extends to those with and without VMS, as well as those with related comorbidities such as sleep disorders and cardiovascular disease.

Most important findings

The review’s central finding is that VMS, hot flashes, and night sweats are likely not merely transient symptoms of hormonal withdrawal, but rather indicators of underlying neurovascular dysregulation that may predispose women to chronic conditions of aging. Across countries, four distinct patterns of VMS (varying by onset, severity, and duration) recur, suggesting a biological underpinning rather than cultural artifacts. Notably, severe or persistent VMS are associated with increased risks for sleep disturbances (e.g., insomnia, obstructive sleep apnea), mood and cognitive disorders, and cardiovascular conditions such as endothelial dysfunction and coronary artery calcification. Genetic studies implicate variants in genes governing estrogen synthesis, metabolism, and signaling, as well as noradrenergic and serotonergic pathways, as contributors to individual susceptibility and symptom patterns. Evidence points toward disruption in hypothalamic KNDy neuron signaling and altered autonomic outflow (both sympathetic and parasympathetic) as mechanistic drivers. Pharmacological interventions targeting neurokinin B receptors, and established therapies such as menopausal hormone therapy (MHT), show variable efficacy depending on individual neurovascular profiles. The review highlights the limitations of self-reported symptom scales and the need for objective, standardized assessment tools.

Key implications

Reframing VMS as signs of autonomic neurovascular dysregulation rather than simply menopausal symptoms has pivotal clinical and research implications. It advocates for a more nuanced, mechanism-based approach to assessing and managing midlife women, particularly in stratifying risk for chronic diseases like cardiovascular disease, dementia, and osteoporosis. This perspective supports the development of personalized interventions, potentially informed by genetic and autonomic profiling, and underscores the need for investment in objective monitoring technologies and longitudinal studies.