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.
BACKGROUND
Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease.


OBJECTIVE
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 11nmol/L or free T at or below 250pmol/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 1,000mg (every 12 weeks) or placebo (PLB) gel (3-6 g/daily) for 24 months.


METHODS
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.
Aversa
Antonio
A
Department of Medical Pathophysiology, Sapienza University of Rome, Italy. antonio.aversa@uniroma1.it
Bruzziches
Roberto
R
Francomano
Davide
D
Rosano
Giuseppe
G
Isidori
Andrea M
AM
Lenzi
Andrea
A
Spera
Giovanni
G
D000728:Androgens / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000517:prevention & control*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004311:Double-Blind Method; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000188:drug therapy*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D012307:Risk Factors; D013739:Testosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055105:Waist Circumference / Q000187:drug effects
D000728:Androgens; D001786:Blood Glucose; D013739:Testosterone; C010792:testosterone undecanoate