OC45 Polycystic ovarian syndrome in adolescents: utilising discovery proteomics to identify novel non-invasive biomarkers

Abstract

Background Polycystic ovarian syndrome (PCOS) is the most common hormone disorder in females, affecting 4–20% of the population. PCOS is associated with metabolic dysfunction, pro-inflammation and mood disorders. Despite this, it is poorly understood, and diagnosis and management remain challenging in adolescents. Proteomics enables a better understanding of disease mechanisms and facilitates the identification of novel biomarkers. Aims 1. To better understand the clinical phenotype of PCOS in adolescents. 2. To undertake discovery proteomic urine profiling using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to identify novel non-invasive biomarkers of PCOS. Method In this prospective longitudinal study, females aged 12–19 years meeting NIH diagnostic criteria for PCOS were recruited from adolescent endocrine and gynaecology clinics. At baseline and annual follow-up, the following were measured: pituitary, adrenal and ovarian hormones, anti-Mullerian hormone, inflammatory and metabolic markers including an oral glucose tolerance test, psychometric questionnaires, menstrual records, pubertal assessment, anthropometric parameters and pelvic ultrasounds. We have undertaken UPLC-MS/MS and developed new methods for discovery proteomic profiling of urine samples in an attempt to identify new disease mechanisms, drug targets and potential biomarkers. Results To date, 37 participants have been recruited (median age 15.0 years, range 12.6–18.3), and 22 have completed annual follow-up. Clinical signs at presentation included acne (89%), hirsutism (78%), acanthosis nigricans (49%) and overweight/obesity (81%). Two-thirds of participants had depressive or anxiety symptoms. Only one-third were known to mental health services. Metabolic dysfunction was common; elevated body fat (88%), dyslipidaemia (24%), insulin resistance (62%), and impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (40%). AMH was elevated in one-third of participants and three-quarters had an elevated free androgen index. Elevated inflammatory markers (CRP/ESR) were present in 40% participants. Only three participants had definitive ultrasonographic evidence of PCOS. Interventions included lifestyle advice only (27%), combined oral contraceptive pill (COCP) ± anti-androgen (16%), metformin (30%) or metformin + COCP ± anti-androgen (27%). Conclusion and Future Directions Diagnosing PCOS in adolescents remains challenging; acne and irregular menstrual cycles are common and ultrasonographic diagnosis of PCOS is suboptimal. Given the high prevalence of metabolic and mental health disorders, early diagnosis and intervention are imperative. We describe the use of urinary proteomics to study metabolic pathways affected in PCOS and the potential identification of novel non-invasive biomarkers. Subsequently, we will use this hypothesis-generating data-set to create a non-invasive and clinically translatable assay to aid diagnosis and stratify management of this common adolescent condition.