Introduction: Oral testosterone was found to reduce plasma levels of HDL cholesterol. No previous study has examined the effect of fibrates, known to increase HDL cholesterol, in patients with low testosterone levels requiring testosterone replacement. AimsThe study included three age-, weight-, and lipid-matched groups of older men with atherogenic dyslipidemia and late-onset hypogonadism, treated with oral testosterone undecanoate (120mg daily, n=15), micronized fenofibrate (200mg daily, n=15), or testosterone plus fenofibrate (n=18). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 16weeks of therapy. ResultsApart from an increase in plasma testosterone and a reduction in HDL cholesterol, testosterone undecanoate tended to decrease hsCRP and to improve insulin sensitivity. Fenofibrate administered alone increased HDL cholesterol, reduced triglycerides, decreased insulin resistance, reduced circulating levels of uric acid, hsCRP, and fibrinogen, as well as increased plasma levels of homocysteine. The strongest effect on testosterone, HOMA1-IR, uric acid, hsCRP, and fibrinogen was observed if fenofibrate was administered together with testosterone. Testosterone-fenofibrate combination therapy was also devoid of unfavorable effect on HDL cholesterol and homocysteine. ConclusionsOur study shows that fenofibrate produces a stronger effect on cardiometabolic risk factors in men with late-onset hypogonadism and atherogenic dyslipidemia than oral testosterone undecanoate. The obtained results suggest that this group of patients may benefit the most from the combined treatment with oral testosterone undecanoate and micronized fenofibrate.