Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study

Abstract

AbstractBackground and purposeParkinson disease (PD) presents relevant sex‐related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human‐based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical–pathological features in male PD patients.MethodsA cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α‐synuclein, amyloid‐β‐42, amyloid‐β‐40, total tau, and phosphorylated‐181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3‐T magnetic resonance imaging for further correlations. A control group of 56 age‐matched individuals was enrolled for comparative analyses.ResultsMale PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society–Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α‐synuclein and right globus pallidus volume. FSH and LH had age‐dependent correlations with cognitive impairment and CSF amyloid‐β‐42/amyloid‐β‐40 ratio.ConclusionsThe study suggested that sex hormones could differentially contribute to clinical–pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age‐dependent phenomena of amyloidopathy and cognitive decline.