Vasomotor symptoms, cortisol awakening response in perimenopause


Women who were in the top third of hot flash severity showed a 67% increase in cortisol, whereas those in the bottom third of hot flash severity showed only a 30% increase.

Women who reported more frequent and severe hot flashes had a smaller increase in the stress hormone cortisol after waking up, according to a prospective study in the journal Menopause.1

“Research has observed a relationship between more severe hot flashes and an increased risk for cardiovascular disease, but the mechanisms underlying that relationship are unknown,” said principal investigator Jennifer Gordon, PhD, an associate professor of psychology at the University of Regina in Saskatchewan, Canada.

“Alterations in the stress axis, or hypothalamic-pituitary-adrenal (HPA) axis, have been proposed to be an underlying mechanism. Thus, this study aimed to look at the connection between hot flashes and activation of the HPA axis.”

A total of 101 perimenopausal women, ages 45 to 55 years, from Regina, completed a 24-hour hot flash diary assessing frequency and severity of vasomotor symptoms (VMS), once a week for 12 weeks.

Participants also provided two saliva samples weekly for the measurement of the cortisol awakening response (CAR): immediately upon waking and 30 minutes postwaking. A urine sample was also collected weekly for the measurement of a urinary metabolite of estradiol and progesterone: estrone-3-glucuronide and pregnanediol glucuronide, respectively.

General linear models examined the between-subject relationship of mean VMS symptoms and mean CAR, whereas multilevel modeling was used to examine the relationship between within-person weekly changes on weekly CAR.

Although within-subject weekly change in VMS bother, frequency, and severity were not significantly related to weekly CAR, there were several significant changes in between-subject effects of VMS on the CAR. As a result, the total number of hot flashes, overall VMS severity and VMS bothersome were each significantly associated with a blunted CAR.

Outcomes remained significant, despite statistically adjusting for levels of estrone-3-glucuronide, pregnanediol glucuronide, and self-reported sleep quality.

“Because research examining the relationship between hot flashes and cortisol has been mixed so far—some found a relationship, some did not—I really did not know what to expect,” Dr. Gordon told Contemporary OB/GYN. “Our study has the advantage of measuring hot flashes and cortisol a total of 12 times, which might have allowed us to see a relationship where other studies have not.”

The increase in cortisol that occurs when a person wakes up is considered adaptive, according to Dr. Gordon, noting that it is a healthy response and believed to be the body's way of preparing for the day.

“But a smaller increase in cortisol has been linked to an increased risk for cardiovascular disease,” she said. “So the fact that women with more hot flashes have a smaller increase in cortisol in the morning supports the idea that dysregulation of the HPA axis may play a role in linking hot flashes with an increased risk for cardiovascular disease.”

Study results also indicate that treating hot flashes may have benefits for women's cardiovascular health.

However, because the study was observational, “more research is needed to determine whether hot flashes cause a change in the activation of the HPA axis or whether it is the other way around,” Dr. Gordon said.


Dr. Gordon reports no relevant financial disclosures.


  1. Sauer T, Tottenham LS, Ethier A, et al. Perimenopausal vasomotor symptoms and the cortisol awakening response. Menopause. Published online June 22, 2020. doi:10.1097/GME.0000000000001588
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