Influence of Male Hormones on Regional Fat Metabolism
Condition: Obesity
Study type: Interventional
Phase: Phase 1

Summary: 
      The male sex hormone, testosterone, plays an important role in determining body fat
      distribution in men. This is especially evident in the dramatic shift in body composition as
      boys and girls reach sexual maturity. Normal weight women have twice the body fat of a normal
      weight man (30% vs. 15% on average) and men will have twice the stomach fat as women (10% vs.
      5% of fat as intra-abdominal, men vs. women). These are likely sex-steroid linked events.
      Short and long term changes in regional fat distribution accompany testosterone deficiency
      and can be reversed by testosterone replacement. Testosterone deficient men have increased
      stomach fat that can be reversed with testosterone replacement therapy. Interestingly, the
      mechanism by which testosterone affects where we store fat is unknown. It is important to
      understand how testosterone influences where we store fat as it is well established that
      increased stomach fat results in elevated disease risk.

      The proposed study aims to examine the effect of short term, temporary testosterone decreases
      on how and where men store fat. The investigators will compare fat storage between men given
      Lupron to temporarily decrease testosterone levels those that receive Lupron plus
      testosterone replacement vs. a no treatment control group. Comparing these three groups will
      allow us to understand the effects of testosterone on short-term changes in fat tissue
      function that lead to the long-term changes in where we store body fat.
    

Detailed description: 
      There are 3 groups to which you might be assigned. Assignment to these groups is random (ie.
      by flip of a coin).

      If you are assigned to…

        -  Group 1 - you will receive no treatments.

        -  Group 2 - you will be given an injection of leuprolide acetate (Lupron) which will
           temporarily lower sex hormones. This injection will be given two times during the 7 week
           treatment period.

        -  Group 3 - you will be given the injections of Lupron but after the second injection, you
           will also be required to apply a testosterone gel that will result in maintenance of
           your testosterone levels. The testosterone gel is rubbed on the upper shoulders, similar
           to putting on suntan lotion. You will be shown how to put this on.

      If you are in group 2 or 3 you will be given testosterone gel, a male hormone, at the end of
      the study to help prevent symptoms such as hot flashes, until your body has time to return to
      its pre-study hormone levels. This can take up to 4 weeks.

      In addition to the treatment period, you will also:

        -  If you are in group 1, have 4 fat biopsies that are like a miniature liposuction. The
           investigators numb the skin before doing the biopsies. If you are in group 2 or 3, you
           will also have 1 muscle biopsy at the end of the treatment period. In addition, if you
           are in group 2 or 3, you will also have a fat and muscle biopsy before you start the
           hormone treatment.

        -  All groups will need to spend two days and nights in the Clinical Research Unit of the
           Mayo Clinic and your meals will be provided by the for 5 days beforehand. You will also
           need to spend one morning undergoing some initial tests.

        -  You will have your body fat measured before and after the hormone treatment using x-ray
           like equipment that will expose you to some radiation.

        -  Our measures of fat metabolism use molecules that have a small amount of radioactivity.

      Remuneration is provided.
    

Intervention name(s): Leuprolide; Testosterone
Intervention type(s): Drug; Drug
Intervention description(s): 7.5 mg - 1 month depot, 2 doses over 7 weeks; 7.5g - 1% testosterone gel, daily x 7 weeks
Other intervention name(s): Lupron; AndroGel
Intervention MeSH terms: Leuprolide; Testosterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Regional Fat Storage; Fat Oxidation; Testosterone; Male