Testosterone Replacement in Metabolic Syndrome and Inflammation

University of Roma La Sapienza82 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hypogonadism Metabolic Syndrome Obesity Erectile Dysfunction

Interventions

TestosteroneDRUG

Testosterone transdermal gel 50 mg/day (5 gr)

PlaceboDRUG

Placebo transdermal gel (5 gr)

Eligibility

Sex: MALEMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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 (2)

Policlinico Umberto I Hospital - Sapienza University

Rome, Rome, Italy

Dipartimento di Fisiopatologia Medica - Policlinico Umberto I

Rome, Italy

Outcomes

Primary Outcomes

Fat-Free Mass (kg)

Estimate of within subject absolute change in fat-free mass measured by DEXA (dual energy x-ray absorptiometry) at 3 months (90 days) interval during active or placebo treatment.

Time frame: 3 months

Secondary Outcomes

Fat Mass (kg)

Estimate of within subject absolute change (Kg) in fat mass measured by DEXA at 3 months (90 days) interval during active or placebo treatment.

Time frame: 3 months

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

Estimate of within subject absolute change in measure of insulin resistance homeostatic model HOMA-IR.

Time frame: 3 months

CRP (C reactive protein)

C reactive protein (High sensitivity).

Time frame: 3 months

Interleukins

Within subject absolute and percentage change in serum: IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa (tumor necrosis factor alpha)

Time frame: 3 months

Adipokines

Estimate of within subject absolute change in serum: ADIPONECTIN, LEPTIN, RESISTIN.

Time frame: 3 months

Waist circumference

Waist circumference (cm)

Time frame: 3 months

IIEF

International Index of Erectile Dysfunction

Time frame: 3 months

Data from ClinicalTrials.gov

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