Sex- and age-specific reference intervals for diagnostic ratios reflecting relative activity of steroidogenic enzymes and pathways in adults

PLoS One. 2021 Jul 8;16(7):e0253975. doi: 10.1371/journal.pone.0253975. eCollection 2021.

Abstract

Objective: Diagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking.

Methods: Sixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature.

Results: Most ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night.

Conclusions: Sex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Enzymes / metabolism*
  • Female
  • Humans
  • Male
  • Metabolic Networks and Pathways*
  • Metabolome
  • Middle Aged
  • Reference Values
  • Sex Characteristics*
  • Steroids / metabolism*
  • Steroids / urine
  • Young Adult

Substances

  • Enzymes
  • Steroids

Grants and funding

This work was supported by the Swiss National Science Foundation (grant number 33CM30-124087 to MB, http://p3.snf.ch/Project-124087). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.