Effects of Testosterone Undecanoate on Cardiovascular Risk Factors and Atherosclerosis in Middle-Aged Men with Late-Onset Hypogonadism and Metabolic Syndrome: Results from a 24-month, Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Introduction Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease. Aim To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11 nmol/L or free T at or below 250 pmol/L). Methods This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57 ± 8) were randomized (4:1) to receive TU 1,000 mg (every 12 weeks) or placebo (PLB) gel (3–6 g/daily) for 24 months. Main Outcome Measures Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP). Results At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P <0.001), CIMT (P <0.0001), and hsCRP (P <0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P <0.0001) and 58% (P <0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P <0.0001), visceral fat mass (P <0.0001), and improvement in HOMA-IR without changes in body mass index (BMI). Conclusions TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events.

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

“…However, the majority of participants were hypertensive, which may have been exacerbated by the high testosterone dose used. Another recent study of 50 middle-aged hypogonadal men randomised to intramuscular testosterone undecanoate or placebo for 24 months did not report any cardiovascular safety concerns (37).…”

Чоловічий Гіпогонадизм (Частина 2)

“…Лікування Т в осно-вному впливає на композицію тіла, знижуючи жи-рові маси, індекс маси тіла і ОТ, підвищуючи пісні жирові маси, м'язову масу та силу, покращує ліпід-ний і глікемічний контроль, настрій та пізнання [1,25,26], знижує показники смертності у чолові-ків [27]. Вважають, що прийом Т може відігравати антиатерогенну роль, призводячи до збереження цілісності ендотеліальних клітин і клітин гладень-ких м'язів.…”

Does testosterone supplementation increase PDE5-inhibitor responses in difficult-to-treat erectile dysfunction patients?

“…In man, the increasing evidence that T is a foe for the heart needs to be revisited [17]; in fact, an inverse relationship between T levels, the severity of atherosclerosis and carotid intima-media thickness exists. Accordingly, T administration has demonstrated beneficial effects on vascular reactivity, inflammation, cytokines profile, molecular adhesion, insulinresistance, lipid profile and surrogate markers of atherosclerosis [18]. Furthermore, chronic TRT improves anginal symptoms to cardiac stress test and represents a promise in the treatment of heart failure associated with hypogonadism [19].…”