Endocrine biomarkers and symptom clusters during the menopausal transition and early postmenopause

Abstract

Objective During the menopausal transition and early postmenopause participants in the Seattle Midlife Women's Health Study (SMWHS) were likely to belong to one of three symptom severity classes: severe hot flashes with moderate sleep, mood, cognitive, and pain symptoms (High-severity Hot Flash); moderate levels of all but hot flashes (Moderate Severity); and low levels of all (Low Severity). We tested models of differential effects of hypothalamic-pituitary-ovarian (HPO), hypothalamic-pituitary-adrenal (HPA), and autonomic nervous system (ANS) biomarkers on the three symptom severity classes. Methods SMWHS participants recorded symptoms monthly in diaries and provided overnight urine samples several times per year that were analyzed for estrone, follicle stimulating hormone, cortisol, testosterone, epinephrine and norepinephrine. Multilevel latent class analysis with multinomial regression was used to determine the effects of HPO, HPA, and ANS biomarkers on symptom severity class membership. Results Having lower estrogen levels and higher FSH levels were associated significantly with belonging to the High-severity Hot Flash vs the Low Severity class. Having lower epinephrine and higher norepinephrine levels increased the likelihood of belonging to the High-severity Hot Flash vs the Low Severity class. Having lower epinephrine levels was associated significantly with belonging to the Moderate Severity vs the Low severity class. Cortisol and testosterone were unrelated to symptom severity class membership. Conclusion Association of HPO biomarkers (estrogen, FSH) with the High-severity Hot Flash class was anticipated based on prior hot flash research and associations of HPA biomarkers were as expected based on earlier laboratory studies. Association of lower epinephrine levels with the Moderate Severity class suggests these symptoms may be mediated by the ANS.

Symptom clusters among MsFLASH clinical trial participants

“…Woods and colleagues found that levels of urinary estrone, FSH, epinephrine, and norepinephrine differentiated the three symptoms clusters identified in their earlier analyses. 1,2 Women in a cluster including severe hot flashes had higher overnight norepinephrine and FSH levels and lower estrone and epinephrine levels than those with low severity symptoms. 2 In addition women’s progression through the menopausal transition stages to the late menopausal transition and early postmenopause resulted in a greater likelihood of a symptom cluster with high severity hot flashes.…”

“…1 In addition, higher FSH, lower estrone, higher norepinephrine and lower epinephrine levels were associated with cluster 1. 2 …”

Menopause, symptom clusters, and the complexity of women's lives

“…For example, we found that the symptom cluster in which hot flash was the most severe and dominant symptom was related to having lower levels of urinary estrone, higher levels of follicle stimulating hormone, lower epinephrine, and higher norepinephrine levels, suggesting that this cluster of symptoms may be mediated by both ovarian steroids and the autonomic nervous system. 6 This same cluster was more likely to occur during the late menopausal transition and early postmenopause, and was associated with a variant in the 17 hydroxysteroid dehydrogenase (HSD) gene polymorphism, as well as higher levels of stress, than observed in the low-symptom-severity cluster (unpublished data).…”

Symptom Cluster Research With Biomarkers and Genetics Using Latent Class Analysis

“…For example, when using LCA for symptom clusters, LCA identifies groups of people who have a similar symptom experience. LCA has been successfully used to determine symptom cluster membership in various patient populations including myocardial infarction 15 , cancer 16,17 , and the menopause transition 18 …”