Testosterone reference ranges in women, adolescent girls, and children: the 2024 PCOS Challenge-CDC stakeholder meeting.

CONTEXT: Testosterone measurement is fundamental to the management of many disorders in women, adolescent girls, and children, most notably androgen excess, including polycystic ovary syndrome (PCOS, aka polyendocrine metabolic ovarian syndrome [PMOS]) and congenital adrenal hyperplasia, and androgen deficiency disorders. Despite 2 decades of progress in testosterone assay standardization, pediatric and adult female reference intervals (RIs) remain highly variable across laboratories and assay systems, limiting diagnostic accuracy and clinical decision-making.

OBJECTIVE

On August 26, 2024, PCOS Challenge: The National Polycystic Ovary Syndrome Association, in collaboration with the Centers for Disease Control and Prevention (CDC) Clinical Standardization Programs, convened a stakeholder meeting.

RESULTS

Participants reviewed the historical trajectory of testosterone standardization, clinical need for sex- and age-specific RI, current RI limitations, technical challenges of measuring testosterone at female and pediatric concentrations, and a validated methodology for normalizing and combining data across existing cohorts using CDC reference measurements. Nine women's and adolescent health cohorts were identified as candidates for RI development, and an estradiol RI precedent was presented as proof of concept using the same data harmonization approach.

CONCLUSION

Recommendations across 7 domains were proposed: (1) assay standardization, (2) reference population characterization, (3) study design parameters, (4) data integration standards, (5) educational outreach, (6) global access, and (7) need for standardized RI for additional relevant biomarkers, including Anti-Müllerian Hormone and 11-oxygenated androgens. A 4-phase work plan was proposed for cohort identification, specimen re-analysis at the CDC laboratory, statistical analysis, and peer-reviewed publication of the resulting RI.