Effects of Testosterone Gel on Carbohydrate and Lipid Metabolism In Elderly Obese Men
Condition: Aging; Obesity; Insulin Resistance; Hypogonadism
MeSH terms: Obesity; Insulin Resistance; Hypogonadism
Intervention: Topical testosterone gel 10 g/day
Intervention description: Testosterone gel therapy for 20 weeks
Intervention MeSH terms: Testosterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: No masking. This was an open label (un-blinded)
Enrollment: 22.0
Sex: Male
Minimum age: 60 Years
Maximum age: 90 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Aging; Older men; Abdominal obesity; Central obesity; Insulin resistance; Low testosterone

Summary:

      A. HYPOTHESES: In older men low testosterone levels, abdominal obesity and elevated fasting
      insulin who are at risk for the cardiovascular complications such as heart attack and stroke.

        1. Supplemental testosterone will decrease abdominal adipose tissue and hepatic fat) and
           appendicular fat and intramyocellular lipid in peripheral muscles (IMCL).

        2. Supplemental testosterone will improve insulin sensitivity by:

             1. Decreasing hepatic glucose output (HGO), a measure of central insulin resistance

             2. increasing peipheral glucose disposal (Rd), a measure of periperal insuln
                sensiivity

             3. . Improving peripheral glucose disposal (Rd) by reducing IMCL

             4. Increasing appendicular skeletal muscle mass

      B. OBJECTIVES:

        1. Primary Objective: To determine the effects of supplemental testosterone to achieve
           testosterone levels in the upper normal physiologic range on central adipose tissue
           (abdominal and hepatic fat) and peripheral skeletal muscle fat (appendicular fat and
           IMCL).

        2. Secondary Objectives: To determine the effects of supplemental testosterone to achieve
           testosterone levels in the upper normal physiologic range:on central insulin sensitivity
           ( hepatic glucose output ([HGO]) and peripheral insulin sensitivity (glucose disposal
           (Rd)

      Results of this study will provide greater understanding whether androgen therapy enhances
      insulin sensitivity by decreasing HGO, improving peripheral Rd and if these desired effects
      are achieved, whether they are due to reductions in abdominal fat or liver lipid, IMCL or
      effects of augmenting muscle mass per se.

      Results will generate hypotheses to investigate cellular and molecular mechanisms of androgen
      effects in persons at risk for the Metabolic Syndrome.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Entry Criteria:

          -  Men > 60 years of age

          -  Total testosterone < 300 ng/dL

          -  Waist circumference >102 cm

          -  Fasting insulin level > 18 U/L

        Exclusion Criteria:

          -  PSA > 4.1, symptoms of obstructive uropathy (AUA score > 14), unexplained prostate
             nodule or gland firmness

          -  Hematocrit > 50%

          -  Malignancy other than cutaneous cancers

          -  Sleep apnea requiring CPAP

          -  History of myocardial infarction, angina or stroke within the previous 6 months

          -  Clinical diagnosis of diabetes or FPG > 126 mg/dL

          -  Hypothyroidism not controlled to euthyroid levels with medication for at least 3
             months

          -  LDL-C >160 mg/dL

          -  Transaminases > 1.5X ULN

          -  Systemic anticoagulation with warfarin

          -  Active progressive resistance training

          -  Dieting for weight loss

          -  Active inflammatory condition (e.g. rheumatoid arthritis)

          -  Use of any anabolic agent (e.g. growth hormone, testosterone precursor, anabolic
             steroid)or cytokine therapy in the proceeding 12 months