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.