Background: Polycystic ovarian syndrome (PCOS) is the most common hormone disorder in adolescent and young adult females, affecting 420% of the population. PCOS is associated with metabolic dysfunction, pro-inflammatory processes and mood disorders. Despite this, it is poorly understood in younger adolescents, and diagnosis and management remain challenging.
Objectives: To better understand the clinical phenotype of PCOS in adolescents. Subsequently, we will undertake proteomic and metabolomic (omic) profiling of urine to identify novel non-invasive biomarkers of PCOS.
Method: In this prospective longitudinal study, females aged 1219 years meeting NIH diagnostic criteria for PCOS were recruited from adolescent endocrine and gynaecology clinics (July 2016November 2017). At baseline and annual follow-up, pituitary, adrenal and ovarian hormones were analysed by radioimmunoassay and mass spectrometry. Anti-müllerian hormone, inflammatory and metabolic markers were measured including an oral glucose tolerance test. Psychometric questionnaires, menstrual records, pubertal assessment, anthropometric parameters and trans-abdominal pelvic ultrasounds were undertaken. Urine samples were obtained for shotgun omic profiling using Electrospray-Ionisation Quadrupole-Time-of-Flight Mass Spectrometry.
Results: To date, 37 participants have been recruited (median age 15.0 years, range 12.618.3 years), and 17 have completed their 12 month follow-up. Clinical signs at presentation included acne (89%), hirsutism (78%), acanthosis nigricans (49%), obesity (57%; BMI Z score >2) and overweight (24%; BMI Z score >1). Two-thirds of participants had symptoms of depression or anxiety but only one-third were known to mental health services. Metabolic dysfunction was common at baseline; 88% of participants had an elevated body fat percentage, 24% had hypercholesterolaemia or hypertriglyceridaemia, 29% had impaired fasting glucose or impaired glucose tolerance, one had undiagnosed type 2 diabetes and 62% had insulin resistance. AMH was elevated in one-third of participants (median AMH 34.1 pmol/l, range 5.0116.0 pmol/l) and three-quarters had an elevated free androgen index. Elevated inflammatory markers (CRP/ESR) were present in 40% participants. Only three participants had ultrasonographic evidence of PCOS and a further quarter had equivocal results.
Conclusion and future directions: Diagnosing PCOS in adolescents remains challenging as acne and irregular menstrual cycles are common, and ultrasonographic diagnosis of PCOS is suboptimal. However, prevalence of mental health disorders and metabolic disease is high. Therefore, accurate diagnosis and early intervention are imperative. Whilst promising biomarkers, including AMH have been noted, our omic analysis aims to identify a wider range of novel non-invasive biomarkers. Subsequently, we aim to create a clinically translatable assay to aid diagnosis and management of this common adolescent condition.
27 Sep 2018 - 29 Sep 2018