A Literature Overview of Age- and Tanner Stage-Specific Reference Intervals for Sex Hormones for Children Aged 0-18 Years.

This study aims to provide a comprehensive overview of age- and Tanner stage-specific reference intervals (RIs) for testosterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) in children and adolescents and to highlight the importance of age- and Tanner stage-specific RIs for clinical practice. A literature review was performed to identify studies reporting RIs on testosterone and estradiol quantified using GC-MS/MS or LC-MS/MS and LH, FSH, and SHBG quantified using immunoassays in healthy individuals aged 0-18 years, categorized by age and/or Tanner stage. Sample sizes were evaluated according to the Clinical Laboratory Standards Institute (CLSI) guideline CLSI EP28-A3c, with ≥120 samples per group being acceptable, 39-119 samples being poor, and ≤38 samples being unacceptable. Analytical methods and statistical approaches were carefully documented. Fourteen studies were included for testosterone, seven for estradiol, thirteen for LH and FSH, and nine for SHBG. The results revealed considerable variability in the availability and quality of RIs, with many studies lacking adequate sample size or appropriate partitioning. Testosterone, estradiol, LH, and FSH RIs demonstrated significant changes during mini-puberty and puberty, with clear sex-specific patterns. SHBG RIs fluctuated throughout childhood and adolescence. This literature review demonstrates that RIs for HPG axis hormones show significant changes during mini-puberty and puberty, although data using appropriate analytical methods, using sufficient sample sizes, and reporting on age categories, Tanner stage, and menstrual cycle phase are scarce. Robust age- and Tanner stage-specific RIs are essential to improve diagnostic accuracy and individualized care in children and adolescents.