Vascular Ageing in Conditions Associated With Early Onset Hypogonadism

INTRODUCTION: Early-onset hypogonadism may increase the risk of early vascular ageing (EVA). METHODS: Boys with conditions linked to intrauterine hypogonadism-Klinefelter syndrome (KS) and hypospadias-were recruited alongside healthy controls. Assessments included clinic blood pressure (BP), flow-mediated dilatation, carotid intima-media thickness (CIMT), and pulse wave velocity (PWV). Fasting blood tests measured testosterone, anti-Müllerian hormone, luteinising hormone, follicle-stimulating hormone, triglycerides, glucose, and cholesterol. Oxidative stress and epigenetic markers were evaluated using total antioxidant capacity (TAOC), peroxide, oxidative stress index (OSI), 8-hydroxy-2'-deoxyguanosine (8OHdG), thiobarbituric acid reactive substances (TBARS), glutathione, alpha klotho protein, histone H3 modification, telomerase, and DNA methyltransferase (DNMT) activity. RESULTS: Eleven boys per group were studied (median age 14.5 years). Systolic BP was higher in KS and hypospadias compared with controls. CIMT and pulse pressure were elevated in hypospadias versus controls. Mean arterial pressure was increased in KS. Oxidative stress markers (TBARS, TAOC, peroxide, OSI) were higher in hypospadias. 8OHdG was elevated in hypospadias versus controls but lower than in KS. DNMT activity was increased in both KS and hypospadias. No differences were observed in alpha klotho, histone H3 modification, or telomerase. CONCLUSIONS: Adolescents with early-onset hypogonadism show evidence of EVA, with associated oxidative stress and epigenetic alterations warranting further investigation.