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
Summary
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 naïve 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) Interleukins Adipokines Waist circumference IIEF Penile CDU (color Doppler ultrasound) PSA (prostatic specific antigen) Hb, Htc Fat-free mass Fat Mass HOMA-IR CRP Interleukins Adipokines
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Male.
Criteria:
Inclusion Criteria:
- patients with Metabolic Syndrome according to ATPIII
- patients with mild hypogonadism (both testosterone evaluations between 6 and 11
nmol/L)
- 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
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