CDC and PCOS Challenge outline work plan for standardized female and pediatric testosterone reference intervals
Investigators convened a stakeholder meeting with the CDC Clinical Standardization Programs and the PCOS Challenge to address the persistent variability in testosterone reference intervals for women, adolescent girls, and children. The group reviewed technical measurement challenges at low concentrations, evaluated a data harmonization methodology, and identified nine candidate cohorts for reference interval development. The meeting produced recommendations across seven domains, including assay standardization, reference population characterization, and global access, alongside a four-phase work plan for specimen re-analysis and peer-reviewed publication. Standardized reference intervals are critical for improving diagnostic accuracy in androgen excess and deficiency disorders, directly impacting laboratory reporting and clinical decision-making.
The original study
Testosterone Reference Ranges in Women, Adolescent Girls, and Children: The 2024 PCOS Challenge-CDC Stakeholder Meeting.
- Authors
- Ottey S, Pokuah F, Cree M, Sherif K, Vesper HW, Lyle AN, et al.
- Journal
- The Journal of clinical endocrinology and metabolism
- Type
- Journal Article
- PMID
- 42444555
Original abstract
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 two 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: 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 (CSP), 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. CONCLUSIONS: Recommendations across seven 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.