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The Science Behind Hot Flushes

Guest post by Dr Ornella Cappellari

Hot flushes are one of the worst symptoms for women experiencing the menopause. They are unpredictable and overwhelming and they can last quite a long time. As we know, hot flush symptoms negatively impact our quality of life and are one of the major reasons why women seek medical intervention and decide to go for HRT. Up to now, hot flushes are thought to be an inappropriate recruitment of thermoregulatory heat effector responses to a perceived warmth, (in other words a mistake in temperature perception) therefore there is vasodilation and a subsequent drop in core body temperature. Hot flushes often coincide with luteinizing hormone (LH) release. LH release happens when circulating estrogen levels are low. 

Neurons in one specific region of our brain (hypothalamus) express kisspeptin1 and neurokinin B two proteins which are negatively regulated by sex hormones. There is growing evidence now that Kiss1 expressing neurons are linked to LH release in the absence of estrogen. These neurons could be the direct cause of hot flushes. If true, it will be much easier to develop a specific therapy.

A short report in Cell has just been published in which Dr. Padilla and colleagues performed a series of experiments on rodents to establish whether those neurons are involved in hot flushes in menopausal women. Their experiments, in which female rodents were induced to a menopausal state, found that Kiss1 protein has a pulsatile activity pattern with a fixed period that is correlated with peaks of LH release. After all the experiments, they concluded that this pulsatile activity, even if it seems to be related with hot flushes origin, is not enough to explain them.

Hot flushes seem to be caused by numerous sensory and interoceptive cues, for example higher ambient temperature, consumption of spicy food, anxiety, altitude and acute physiological stressors. From this study, scientists conclude that hot flushes occur when excitatory external cues converge to Kiss1 neurons in an episode of endogenous activity. From their experiments, they are able to conclude that transient activation of Kiss1 is sufficient to elicit a hot flush like response. More experiments need to be done, but if this pathway is revealed to be the one responsible for hot flushes, this will pave the route for new therapies, more specific and effective. This is a very important piece of research as it gives an insight into the origin of hot flushes and offers hope to that a specific therapy can be found in the near future.

REFERENCE

Cell Rep.2018 Jul 10;24(2):271-277. doi: 10.1016/j.celrep.2018.06.037.

A Neural Circuit Underlying the Generation of Hot Flushes.

Padilla SL1, Johnson CW2,Barker FD1, Patterson MA1, Palmiter RD3.