Erectile Dysfunction, Hypogonadism, Metabolic Syndrome, Obesity
Conditions
Keywords
Adiponectin, Resistin, Adipocytes, Testosterone, Aging, HOMA-IR, Insulin, Hypogonadism, Metabolic Syndrome, Obesity, Erectile Dysfunction
Brief 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.
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.
Interventions
DRUGTestosterone
Testosterone transdermal gel 50 mg/day (5 gr)
DRUGPlacebo
Placebo transdermal gel (5 gr)
Sponsors
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fat-Free Mass (kg) | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HOMA-IR (homeostasis model assessment)- (insulin resistance) | 3 months | Estimate of within subject absolute change in measure of insulin resistance homeostatic model HOMA-IR. |
| CRP (C reactive protein) | 3 months | C reactive protein (High sensitivity). |
| Interleukins | 3 months | 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) |
| Adipokines | 3 months | Estimate of within subject absolute change in serum: ADIPONECTIN, LEPTIN, RESISTIN. |
| Waist circumference | 3 months | Waist circumference (cm) |
| IIEF | 3 months | International Index of Erectile Dysfunction |
| Fat Mass (kg) | 3 months | Estimate of within subject absolute change (Kg) in fat mass measured by DEXA at 3 months (90 days) interval during active or placebo treatment. |
| PSA (prostatic specific antigen) | 3 months | PSA |
| Hb, Htc | 3 months | haemoglobin and haematocrit |
| Fat-free mass | 6 months | — |
| Fat Mass | 6 months | — |
| HOMA-IR | 6 months | — |
| CRP | 6 months | — |
| Penile CDU (color Doppler ultrasound) | 3 months | Penile Color-Doppler Ultrasonography of cavernosal arteries before and after active or placebo treatment. |
Countries
Italy
Outcome results
None listed