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Testosterone Replacement in Metabolic Syndrome and Inflammation

Information source: University of Roma La Sapienza
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hypogonadism; Metabolic Syndrome; Obesity; Erectile Dysfunction

Intervention: Testosterone (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Roma La Sapienza

Official(s) and/or principal investigator(s):
Vincenzo Bonifacio, MD, PhD, Principal Investigator, Affiliation: Sapienza University of Rome
Andrea M Isidori, MD, PhD, Study Director, Affiliation: Sapienza University of Rome
Andrea Lenzi, MD, PhD, Study Chair, Affiliation: Sapienza University of Rome


Hypogonadism (HG) frequently complicates the Metabolic Syndrome (MetS), whether testosterone replacement (TRT) is beneficial has not been clearly ascertained. This study was designed to address the effects of TRT on insulin resistance, body composition and pro-inflammatory status in na´ve patients with MetS and HG.

Clinical Details

Official title: Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Fat-Free Mass (kg)

Secondary outcome:

Fat Mass (kg)

HOMA-IR (homeostasis model assessment)- (insulin resistance)

CRP (C reactive protein)



Waist circumference


Penile CDU (color Doppler ultrasound)

PSA (prostatic specific antigen)

Hb, Htc

Fat-free mass

Fat Mass





Detailed description: The features of Metabolic Syndrome (MetS) include abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance or glucose intolerance. These symptoms are also frequently found in hypogonadal men. Adipose tissue and androgens in male obesity are reciprocally linked. Total and free testosterone (T) are decreased in proportion to the degree of body fatness while T regulates insulin sensitivity and body composition. As a consequence, hypoandrogenism carries an additional independent risk for cardiovascular and metabolic disorders. Men with type 2 diabetes mellitus (T2D) exhibit lowered T levels that are inversely correlated to HbA1c. In addition, abdominal adiposity causes an impairment of testicular steroidogenesis that is directly linked to circulating adipokines; enhanced cytokine release from macrophage-infiltrated adipose tissue is pivotal to the pathogenesis of insulin resistance and atherosclerosis. Both MetS and T2D share with hypogonadism such a proinflammatory state. For this reason we performed a randomized controlled trial on the effects of TRT on insulin resistance and circulating inflammatory markers in a cohort of middle-aged men with mild hypogonadism and MetS at first diagnosis, that were not taking medications known to influence the investigated outcomes. We established strict criteria for enrollment and used a physiological replacing therapy. Given that testosterone replacement therapy (TRT) determines a reduction of body fat mass paralleled by an increase in fat free mass (6), and that TRT exerts an anti-inflammatory role inhibiting interleukins (IL), in particular the IL-6 gene (14), it remains to be established whether these independent effects also reflect in an improvement in insulin resistance.


Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Male.


Inclusion Criteria:

- patients with Metabolic Syndrome according to ATPIII

- patients with mild hypogonadism (both testosterone evaluations between 6 and 11


- patients naïve to hypoglycemic therapies

Exclusion Criteria:

- patients on hypoglycemic medications

- patients with severe hypogonadism (<5 nmol/L)

- patients with borderline T values hypogonadism (>11 nmol/L)

- patients with contraindication to testosterone therapy: prostate cancer, PSA>4 ng/ml,

severe hepatic or renal insufficiency, Hb>17, Htc>52%, severe urinary retention

Locations and Contacts

Dipartimento di Fisiopatologia Medica - Policlinico Umberto I, Rome 00161, Italy

Policlinico Umberto I Hospital - Sapienza University, Rome 00161, Italy

Additional Information

Related publications:

Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999 Oct;84(10):3673-80.

Aversa A, Isidori AM, Greco EA, Giannetta E, Gianfrilli D, Spera E, Fabbri A. Hormonal supplementation and erectile dysfunction. Eur Urol. 2004 May;45(5):535-8. Erratum in: Eur Urol. 2005 Apr;47(4):564.

Isidori AM, Giannetta E, Pozza C, Bonifacio V, Isidori A. Androgens, cardiovascular disease and osteoporosis. J Endocrinol Invest. 2005;28(10 Suppl):73-9. Review.

Isidori AM, Greco EA, Aversa A. Androgen deficiency and hormone-replacement therapy. BJU Int. 2005 Aug;96(2):212-6. Review.

Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93. Review.

Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A, Lenzi A. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf). 2005 Oct;63(4):381-94. Review.

Isidori AM, Lenzi A. Testosterone replacement therapy: what we know is not yet enough. Mayo Clin Proc. 2007 Jan;82(1):11-3.

Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf). 2003 May;58(5):632-8.

Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rocchietti-March M, Frajese G, Fabbri A. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol (Oxf). 2000 Oct;53(4):517-22.

Starting date: January 2004
Last updated: October 25, 2014

Page last updated: August 23, 2015

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