Metabolomics During Testosterone Therapy
Condition: Testosterone Deficiency
Study type: Observational

Summary: 
      One promising but understudied area in the field of testosterone (T) therapy is its effect on
      metabolism and the development of type II diabetes. Metabolomics is a powerful research tool
      that can detect very early signs of metabolic derangement that may lead to metabolic disease.
      In this observational study, investigators aim to apply metabolomics in order to better
      understand how T therapy influences metabolism. In a clinical population of outpatient men
      with T deficiency investigators will perform comprehensive clinical evaluations and also
      obtain blood for metabolomics. This will be done once prior to T therapy and again after 4-6
      months of T therapy. Investigators hypothesize that they can detect metabolic derangements in
      men with T deficiency and that these derangements will improve with T therapy.
    

Detailed description: 
      One promising but understudied area in the field of T therapy is its effect on insulin
      resistance (IR) and the development of type II diabetes and cardiometabolic disease. Although
      several clinical studies suggest T therapy improves metabolic parameters and may prevent
      disease progression, a mechanism for understanding this process is lacking. Investigators
      propose to use metabolomics to shed light on how metabolic function changes with T therapy.

      Metabolomics is an established investigative tool that measures hundreds of unique chemical
      markers (metabolites) involved in normal and diseased cellular processes from a blood sample.
      Previous studies using the Metabolite Profiling Platform at the Broad Institute of
      Harvard/Massachusetts Institute of Technology applied tandem liquid chromatography-mass
      spectrometry (LC-MS)-based metabolomics to large, population-based cohorts. These studies
      identified and validated highly sensitive signatures of IR that successfully predicted occult
      risk for type II diabetes in clinically normal men. Investigators now plan to apply
      metabolomics to a clinical population in order to obtain a new perspective on the biochemical
      metabolic changes that occur based on a man's testosterone status. Investigators plan to
      study men with symptomatic testosterone deficiency identified at Men's Health Boston (MHB),
      an outpatient men's health clinic.

      In a pilot study involving 32 blood samples, investigators have already identified a specific
      metabolomic signature in men undergoing androgen deprivation therapy for prostate cancer.
      Based on these preliminary results and other recent studies, investigators hypothesize that
      they can detect metabolic derangements in men with T deficiency and that these derangements
      will respond to changes in T levels. Investigators will address this hypothesis though the
      following specific aims:

      Aim 1: To characterize metabolite profiles and evaluate metabolic dysfunction in T deficient
      men

      To accomplish this aim investigators will study T deficient men presenting to MHB. In
      addition to metabolite profiling, these men will undergo a comprehensive clinical evaluation
      at MHB including:

        -  Complete History and Physical exam

        -  Assessment of symptoms of T deficiency and sexual function using validated and other
           questionnaires

        -  Comprehensive hormonal and metabolic laboratory evaluation

        -  Body composition (including visceral and subcutaneous adiposity) by dual x-ray
           absorptiometry (DXA) Investigators will build a reference dataset relating metabolite
           profiles with metabolic risk factors in a clinical population of T deficient men. This
           will include data on the relationship between metabolite profiles and sexual and other
           symptoms of T deficiency. Investigators will also compare concentrations of select
           metabolites between T deficient men and matched eugonadal controls previously studied in
           the Framingham cohort.

      Aim 2: To determine how T therapy influences metabolite profiles and IR

        1. To identify metabolites that change in response to raising serum T

        2. To determine how changes in metabolite profiles relate to changes in IR

        3. To determine how response in terms of sexual function symptoms of low T relate to
           response in metabolite profiles and IR.

      Metabolite profiles will be obtained and clinical evaluation performed (described above under
      Aim1) at baseline and again after 6 months of therapy. Investigators will study interactions
      between changes in sexual function and serum T, IR, body composition and metabolite profiles
      (with particular attention to established metabolite markers of IR).
    

Intervention name(s): Testosterone Therapy
Intervention type(s): Drug
Intervention description(s): In this observational study we will be enrolling testosterone deficient men who intend to undergo testosterone therapy.
Intervention MeSH terms: Testosterone
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Testosterone deficient men who intend to undergo testosterone therapy at an outpatient
        men's health clinic.
      
Biospecimen description: 
      Serum samples obtained for metabolomics
    
Keywords: Hypogonadism; Testosterone Deficiency