Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 2
- 主要终点
- Fat-Free Mass (kg)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Testosterone gel
Testosterone transdermal gel 50 mg/day
干预措施: Testosterone (Drug)
Placebo gel
Placebo gel
干预措施: Placebo (Drug)
结局指标
主要结局
Fat-Free Mass (kg)
时间窗: 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.
次要结局
- PSA (prostatic specific antigen)(3 months)
- Hb, Htc(3 months)
- Fat-free mass(6 months)
- Fat Mass (kg)(3 months)
- HOMA-IR (homeostasis model assessment)- (insulin resistance)(3 months)
- CRP (C reactive protein)(3 months)
- Interleukins(6 months)
- Adipokines(6 months)
- Waist circumference(3 months)
- IIEF(3 months)
- Penile CDU (color Doppler ultrasound)(3 months)
- Fat Mass(6 months)
- HOMA-IR(6 months)
- CRP(6 months)
研究者
Andrea M. Isidori
Professor of Endocrinology
University of Roma La Sapienza