Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men
Condition: Sarcopenia
MeSH terms: Sarcopenia
Intervention: Testosterone injection; Testosterone gel; Medrol
Intervention description: 100 mg single IM injection; Testosterone gel 10 mg. administered topically daily for seven days; Medrol 6 day dose pack with an additional 4mg dose on day 7
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Methyltestosterone; Prednisolone hemisuccinate; Prednisolone phosphate; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Male
Minimum age: 60 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Sarcopenia; Aging muscle; Androgen; Cytokines; Muscle metabolism

Summary:

      Skeletal muscle loss is a common consequence of aging and in some individuals reaches a level
      that compromises health and quality of life. Age-associated increases in cytokine and
      inflammatory signaling may be important contributors to this process.

      The investigators will assess the practical question of whether testosterone injection and
      gel application elicit similar responses. Resistance exercise will be used as a means of
      stimulating both inflammatory and anabolic responses in skeletal muscle. In order to assess
      the effects of testosterone on these responses, subjects will perform resistance exercise on
      two occasions separated by 7 days. The first session will be performed prior to the
      initiation of testosterone and/or medrol therapy and the second session will be performed
      after receiving therapy for 7 days.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age: 60-85

          -  Gender: Male

        Exclusion Criteria:

          -  Exclusionary medications will be an anticoagulant (Coumadin) because of the risk of
             bleeding during the biopsy procedure. Additional medications which will be disallowed
             for participation include: anabolic steroids, nitrates, antihistamines, and
             glucocorticoids.

          -  The subjects must be able to successfully complete an exercise stress test using the
             Bruce protocol . Subjects will be excluded without exercise testing, with a history of
             angina that occurs with exertion or at rest, or a myocardial infarction within the
             last 12 months. Subjects that demonstrate ³0.1 milliVolts (mV) horizontal or
             downsloping ST segment depression, a drop in systolic blood pressure of ³10 mm Hg,
             and/or frequent or repetitive arrhythmias (defined as ³10 premature ventricular
             contractions (PVC)/min, or couplets) during the stress test will be excluded.

          -  Subjects with LDL cholesterol above 200 mg/dL will be excluded .

          -  Any man with a history of breast cancer or prostate cancer, or any indication of an
             occult carcinoma from an elevation of prostate specific antigen (PSA) above 4.0 mg/L
             (53), or severe benign prostatic hypertrophy (BPH) by history (frequent urination,
             reduced stream) will be excluded.

          -  Subjects with liver dysfunction evidenced by a history of hepatitis B or hepatitis C,
             or by a three-fold elevation of liver enzymes (Alk phos, alanine aminotransferase
             (ALT), aspartate amino-transferase (AST) above normal on screening will be excluded
             from the study.

          -  Any subject with a blood pressure on three consecutive measurements taken at one week
             intervals that has a systolic pressure ³ 140 or a diastolic blood pressure ³ 90 will
             be excluded.

          -  Any subject who has a major medical illness such as diabetes, chronic obstructive
             pulmonary disease, or sleep apnea will be excluded. Moreover, subjects will not have a
             recent history of smoking tobacco. Morbidly obese older men (BMI > 35) will also be
             excluded.

          -  Subjects will evidence of kidney disease (serum creatinine > 2.0mg/dl) will be
             excluded from participation.

          -  Any subject with thyroid disease as determined by an abnormal thyroid stimulating
             hormone (TSH) level will be excluded from participation.

          -  Any subject testing positive for HIV will be excluded .

          -  Allergy to iodine, a component of Betadine which is used to prepare the subject's skin
             for invasive procedures, will be cause for exclusion from this study.

          -  Men with serum total testosterone concentrations greater than 500 ng/dL will be
             excluded.

          -  Subjects who engage in high intensity resistance training on a regular basis will be
             excluded.

          -  Subjects with a known coagulation disorder or with clinical evidence indicative of a
             bleeding disorder (easy bruising, "free bleeders") will not be enrolled in this study
             due to potential problems that could arise from muscle biopsy procedures.