Validation of novel biomarkers for the detection of polycystic ovary syndrome in adolescents and young adult women – the PHOEBE study

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, with symptoms manifesting as early as adolescence. Current PCOS diagnosis guidelines intended for adults do not apply to adolescents/young adults. Furthermore, diagnosing PCOS in adolescents is challenging, as diagnostic/pathological features in adult women i.e., acne, irregular cycles, and polycystic ovaries, are consistent with normal pubertal physiologic changes. Recently described novel circulating biomarkers (meteorin-like protein [METRNL], fibroblast growth factor binding protein 1 [FGFBP1], and leukotriene A4 hydrolase [LTA4H]) have shown promise in diagnosing PCOS. These biomarkers were validated retrospectively in two independent cohorts comprising adolescents and adult women; however, the utility of these biomarkers to determine PCOS status has not been validated/verified prospectively in adolescents/young adults. Therefore, the objective of the PCOS in Human adolescent and yOung adult fEmales – Biomarker Evaluation (PHOEBE) study is to prospectively validate METRNL, FGFBP1, and LTA4H as single biomarkers and in combination as ratios (FGFBP1:METRNL and LTA4H:METRNL), the latter having shown improved diagnostic performance over the single biomarkers alone. Methods This prospective, single-center, non-interventional, proof-of-concept study will be conducted at the Erlangen University Hospital, Friedrich Alexander University of Erlangen–Nuremberg, Germany. The study will consist of approximately 380 female participants aged 15–25 years, who consent to all study visit activities. The study population will be divided into two groups comprising adolescents/young adults with signs and symptoms of PCOS (Group 1) and adolescents/young adults who are healthy and have no signs or symptoms of PCOS (Group 2). Serum samples will be collected and analyzed. Thereafter, statistical analysis will be applied and results will be shown using appropriate statistical methods. Discussion This will be the first time that these candidate biomarkers (METRNL, FGFBP1, and LTA4H) and two biomarker ratios (FGFBP1:METRNL and LTA4H:METRNL) are validated in a prospective cohort. These candidate blood-based biomarkers may improve PCOS diagnosis in adolescents/young adults aiding the early detection of PCOS and potentially resulting in the avoidance of adverse associated comorbidities. Trial registration Trial registration number: ClinicalTrials.gov; NCT06642831 (Registration date: 09 October 2024)