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Review
. 2025 Apr 23;12(2):92-132.
doi: 10.1080/23328940.2025.2484499. eCollection 2025.

Effects of menopause on temperature regulation

Marie Gombert-Labedens  1 , Kristine Vesterdorf  2 , Andrea Fuller  3 , Shane K Maloney  2   3 , Fiona C Baker  1   3
Affiliations
Review

Effects of menopause on temperature regulation

Marie Gombert-Labedens et al. Temperature (Austin). .

Abstract

Changes in thermoregulation, notably the emergence of hot flashes, occur during the menopause transition in association with reproductive hormonal changes. Hot flashes constitute the most characteristic symptom of menopause (prevalence of 50-80%), and have a substantial negative effect on quality of life. Here, we review the endocrine changes associated with menopause and the thermoregulatory system and its sensitivity to female sex hormones. We then review current knowledge on the underlying neural mechanisms of hot flashes and how the reproductive and thermoregulatory systems interact in females. We consider the kisspeptin-neurokinin B-dynorphin (KNDy) neuron complex, which becomes hyperactive when estradiol levels decrease. KNDy neurons project from the arcuate nucleus to thermoregulatory areas within the hypothalamic preoptic area, where heat loss mechanisms are triggered, including cutaneous vasodilation and sweating - characteristics of the hot flash. We describe the physiology and measurement of hot flashes and discuss the mixed research findings about thresholds for sweating in symptomatic individuals. We consider the unique situation of hot flashes that arise during sleep, and discuss the relationships between the environment, exercise, and body mass index with hot flashes. We also discuss the unique situation of surgical menopause (with oophorectomy) and cancer therapy, conditions that are associated with frequent, severe, hot flashes. We then provide an overview of treatments of hot flashes, including hormone therapy and targeted neurokinin B-antagonists, recently developed to target the neural mechanism of hot flashes. Finally, we highlight gaps in knowledge about menopausal thermoregulation and hot flashes and suggest future directions for research.

Keywords: KNDy neurons; Menopause; estradiol; hot flashes; hypothalamus; menopause transition; thermoregulation; vasomotor symptoms; women.

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Conflict of interest statement

Dr. Baker is a consultant for Bayer Consumer Care. No potential conflict of interest was reported by the other authors.

Figures

Figure 1.
Figure 1.
Summary of the STRAW criteria [12] showing the reproductive, menopausal transition, and post-menopause stages. The final menstrual period is retrospectively defined after 12 months without periods. Schematic representations of the changes reported in gonadotropin releasing hormone (GnRH) pulses [13], the reproductive endocrine system [13], and the follicular reserve [14] (middle panels). The two bottom panels highlight the hypothesized changes in KNDy neurons in the hypothalamus and narrowing of the inter-threshold zone that has been hypothesized to underlie the emergence of hot flashes across the stages of the menopausal transition and post-menopause, based on the combined work of [15–26] (although, see text for discussion about conflicting data about a narrowing of the inter-threshold zone).
Figure 2.
Figure 2.
Schematic of the relationship between KNDy neurons in the ARC and glutamatergic neurons (VGLUT2 neurons; vesicular glutamate transporter 2) in the MnPO in the central heat defense pathway, and GnRH neurons of the POA in the central reproductive pathway. During menopause, declining levels of estradiol cause hypertrophy of KNDy neurons, which become hyperactive [71,93]. Depolarization of KNDy neurons leads to the release of kisspeptin, which activates the non-KNDy Kiss1R expressing neurons in the ARC, at least in sheep [94]. These neurons release a stimulatory signal back to an, as of yet, unknown receptor on the KNDy neurons, which further stimulates the release of neuropeptides in a positive feedback circuit [80]. The release of NKB and glutamate activates the KNDy neuron network and elicits a synchronized episodic release of kisspeptin, which targets kisspeptin receptors on the soma of GnRH neurons in the MBH in humans and sheep, and the GnRH dendrons in the median eminence in rodents, initiating the pulsatile release of GnRH, with downstream release of LH and FSH, resulting in estradiol production in the ovaries in several species, including humans [66,69,71–73,78,80]. Depending on species, with a brief time lag, the cycle of events that leads to the release of GnRH is terminated by the release of DYN exerting an inhibitory action via KOR on the synchronized activity of KNDy neurons, that terminates the release of glutamate, NKB, and kisspeptin and hence ends the GnRH pulse [80,95,96]. DYN may also act directly on the GnRH soma via KOR, terminating the GnRH pulse in ruminants and rats [97]. When NKB is released in rodents, it also targets VGLUT2 neurons in the MnPO that express NK3R. Depolarization of those VGLUT2 neurons triggers the release of glutamate, which slightly depolarizes adjacent thermoregulatory neurons, thus sensitizing those neurons by bringing them closer to the threshold for an action potential [98,99]. We hypothesize that similar occurs in humans, and that those thermoregulatory neurons thus become more sensitive to afferent input from warm-sensitive neurons in the periphery and core. Triggering of the thermoregulatory neurons activates the heat defense pathway, resulting in cutaneous vasodilation and heat dissipation, i.e. The hot flash.
Figure 3.
Figure 3.
Schematic figure of the physiological changes that occur during a hot flash. Changes in variables are shown for 30 minutes leading up to, and 20 minutes after, a hot flush for abdominal body temperature [18] (although also see [180], which did not find this increase), forehead skin temperature [175], esophageal temperature [175], mean skin temperature calculated from thermistor probes on the chest, upper arm, thigh, and lower leg [18], sternal skin conductance [18], finger blood flow [175], foot skin blood flow [177], heart rate [175], heart rate variability [53], skin sympathetic nerve activity [177], and LH [181].
Figure 4.
Figure 4.
Schematic figure of the changes over the course of a day, in Tcore in symptomatic and asymptomatic individuals, and number of hot flashes reported by Freedman et al., in 1995 [24], as well as the average frequency of hot flashes across day and night periods reported by Thurston et al., in 2005 [203], and distribution of melatonin levels across 24-hours [218]. In both studies, hot flashes were detected from sternal skin conductance monitoring.
Figure 5.
Figure 5.
Physiological changes that occur across a nocturnal hot flash. This figure is based on the results of a study that examined changes in heart rate and blood pressure across hot flashes that occurred during undisturbed sleep (dark line) and hot flashes that were associated with an awakening or an arousal (light line) [179]. Eighty-six individuals contributed 542 hot flashes for analysis of heart rate and 45 individuals contributed 261 hot flashes for the analysis of blood pressure. Hot flashes associated with arousal/awakening were accompanied by an increase in both systolic and diastolic blood pressure and an increase in heart rate. Hot flashes that occurred in undisturbed sleep were accompanied by a drop in systolic blood pressure and an increase in heart rate, which was of smaller magnitude than that for a hot flash associated with an arousal.
See this image and copyright information in PMC

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