Steroid reference intervals in women: influence of menopause, age and metabolism

Eur J Endocrinol. 2021 Mar;184(3):395-407. doi: 10.1530/EJE-20-1147.

Abstract

Objective: To investigate the impact of age, obesity and metabolic parameters on 13 circulating steroids in reproductive and menopausal age. To define reference intervals (RIs).

Design: Cross-sectional.

Methods: Three hundred and twenty five drug-free, healthy and eumenorrheic women were selected from the general population. Independent relationships of LC-MS/MS-determined steroid levels with age, BMI and metabolic parameters were estimated. Reference sub-cohorts were defined for calculating upper and lower limits in reproductive age, menstrual phases and menopause, and these were compared with limits in dysmetabolic sub-cohorts.

Results: Lower androgens, pro-androgens and estrogens, but higher cortisol and metabolites were found in menopausal compared to reproductive age women. Androgens and precursors decreased during reproductive age (P < 0.001-P = 0.002) but not after menopause. 17OH-progesterone decreased with BMI (P = 0.006) and glucocorticoids with waist circumference (P < 0.001P = 0.002) in reproductive age, but increased with triglycerides (P=0.011P=0.038) after menopause. Inverse associations of dihydrotestosterone with BMI (P=0.004) and HDL-cholesterol (P=0.010), estrone with total cholesterol (P=0.033) and estradiol with triglycerides (P=0.011) were found in reproductive age. After menopause, estrone increased with waist circumference (P<0.001) and decreased with insulin resistance (P=0.012). Ovarian steroid RIs were estimated in menstrual phases and menopause. Age- and reproductive status-specific RIs were generated for androgens, precursors and corticosteroids. Lower limits for reproductive age cortisol (P=0.020) and menopausal 11-deoxycortisol (P=0.003) in dysmetabolic sub-cohorts were reduced and increased, respectively, compared to reference limits.

Conclusions: Obesity and dysmetabolism differently influence circulating steroids in reproductive and menopausal status. Age, menstrual and menopausal status-specific RIs were provided by LC-MS/MS for a broad steroid panel.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / metabolism
  • Blood Chemical Analysis / methods
  • Blood Chemical Analysis / standards*
  • Chromatography, Liquid / standards
  • Cross-Sectional Studies
  • Diagnostic Techniques, Endocrine / standards
  • Energy Metabolism / physiology*
  • Female
  • Gonadal Steroid Hormones / analysis
  • Gonadal Steroid Hormones / blood*
  • Gonadal Steroid Hormones / standards
  • Humans
  • Menopause / blood*
  • Menopause / metabolism
  • Middle Aged
  • Reference Values
  • Sex Factors
  • Tandem Mass Spectrometry / standards
  • Young Adult

Substances

  • Gonadal Steroid Hormones