Perimenopausal vasomotor symptoms and the cortisol awakening response

Objective: Vasomotor symptoms (VMS) are associated with a poorer cardiovascular risk profile. Although the mechanisms underlying this relationship are poorly understood, alterations of the hypothalamic-pituitary-adrenal (HPA) stress axis have been hypothesized to play a role. This study examined the within- and between-subject relationship between VMS and cortisol in a sample of healthy perimenopausal women. Methods: A total of 101 perimenopausal women, ages 45 to 55 years, were included in the study. Once a week for 12 weeks, participants completed a 24-hour hot flash diary assessing frequency and severity of VMS. They also provided two saliva samples for the measurement of the cortisol awakening response (CAR) - immediately upon waking and 30 minutes postwaking - and collected a urine sample 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 between mean VMS symptoms and mean CAR, whereas multilevel modeling was used to examine the relationship between within-person weekly changes on weekly CAR. Results: Within-subject weekly change in VMS bother, frequency, and severity were not significantly related to weekly CAR. Several significant between-subject effects of VMS on the CAR were, however, observed such that total number of hot flashes, overall VMS severity, and VMS bother, were each associated with a blunted CAR. Results remained significant despite statistically adjusting for levels of estrone-3-glucuronide, pregnanediol glucuronide, and self-reported sleep quality. Conclusion: Findings suggest that women who suffer from more severe and bothersome perimenopausal VMS exhibit alterations in HPA axis activity. Within an individual, short-term changes in VMS are, however, not associated with concurrent changes in HPA axis functioning. Further research investigating the role of the HPA axis in linking VMS and increased cardiovascular disease risk is warranted.