Journal of Endocrinological Investigation

, Volume 37, Issue 4, pp 401–411

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study

  • D. Francomano
  • R. Bruzziches
  • G. Barbaro
  • A. Lenzi
  • A. Aversa
Original Article

DOI: 10.1007/s40618-014-0066-9

Cite this article as:
Francomano, D., Bruzziches, R., Barbaro, G. et al. J Endocrinol Invest (2014) 37: 401. doi:10.1007/s40618-014-0066-9

Abstract

Purpose

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 (r2 = −0.46, p < 0.001 and r2 = −0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r2 = 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.

Keywords

Male hypogonadism Testosterone replacement therapy Endothelial function Carotid artery intima-media thickness Epicardial adipose tissue Left ventricular mass and function 

Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  • D. Francomano
    • 1
  • R. Bruzziches
    • 1
  • G. Barbaro
    • 1
  • A. Lenzi
    • 1
  • A. Aversa
    • 1
  1. 1.Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza UniversityRomeItaly

Personalised recommendations