The Impact of Vitamin E Intake on Cardiometabolic Outcomes of Testosterone Replacement Therapy in Men with Late-Onset Hypogonadism

Abstract

Androgen deficiency is associated with an increased risk of cardiometabolic complications, whereas vitamin E may exert protective effects against cardiovascular and metabolic diseases. This pilot prospective cohort study examined whether cardiometabolic outcomes observed during exogenous testosterone therapy differed according to vitamin E intake in men with insufficient endogenous testosterone production. Three cohorts of men with late-onset hypogonadism (LOH) (n = 29 per group), matched for age, smoking status, body mass index, and baseline testosterone concentration, were classified according to vitamin E intake as low, adequate, or high; 29 men without LOH served as controls. Men with LOH received intramuscular testosterone injections every three weeks for six months. Cardiometabolic parameters were assessed before and after treatment, including biochemical markers, carotid intima–media thickness, retinal vascular sclerotic changes, and estimated 10-year cardiovascular risk. Compared with controls, men with LOH had higher HOMA-IR, LDL cholesterol, uric acid, fibrinogen, homocysteine, high-sensitivity C-reactive protein (hsCRP), urinary albumin-to-creatinine ratio (UACR), carotid intima–media thickness, and estimated 10-year cardiovascular risk. Elevations in homocysteine, hsCRP, and UACR were more pronounced in men with low or high vitamin E intake than in those with adequate intake. Testosterone levels increased during treatment in all groups. Improvements were observed in most cardiometabolic parameters in men with adequate vitamin E intake, whereas changes were limited to HOMA-IR in those with low intake. In men with high intake, no significant changes were observed except for a decrease in HDL cholesterol. At study completion, carotid intima–media thickness and retinal vascular sclerotic changes in men with adequate vitamin E intake did not differ significantly from those in controls. Changes in assessed risk factors correlated with increases in testosterone levels and mean daily vitamin E intake. These findings suggest an association between vitamin E intake and cardiometabolic outcomes observed during testosterone therapy in men with testosterone deficiency.