title: Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.
abstract: OBJECTIVE
  Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men.
  
  
  METHODS
  Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters.
  
  
  RESULTS
  At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events.
  
  
  CONCLUSIONS
  In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained.
authors.affiliation: Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Francomano
authors.forename: R
authors.initials: R
authors.lastname: Bruzziches
authors.forename: G
authors.initials: G
authors.lastname: Barbaro
authors.forename: A
authors.initials: A
authors.lastname: Lenzi
authors.forename: A
authors.initials: A
authors.lastname: Aversa
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D004038:Diet, Reducing; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D015444:Exercise; D005340:Fibrinogen / Q000032:analysis; D005951:Glucose Tolerance Test; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000503:physiopathology / Q000628:therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D010865:Pilot Projects; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
chemical_list: D008055:Lipids; D019382:Human Growth Hormone; D013739:Testosterone; D005340:Fibrinogen; C010792:testosterone undecanoate