CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1) Gene and Pharmacogenetics of Response to Testosterone Therapy
Condition: Hypogonadism
MeSH terms: Hypogonadism
Intervention: Testosterone Cypionate
Intervention description: Testosterone cypionate was administered at 200 mg by intramuscular injection every 2 weeks.
DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone.
Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the molecular weight of 412.61.
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 105.0
Sex: Male
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: testosterone

Summary:

      Testosterone (T) replacement prevents bone loss and relieves symptoms associated with
      androgen deficiency in male patients with hypogonadism, but at the expense of an increase in
      prostate-related adverse events and in the hematocrit values above the normal which may lead
      to bad circulatory outcomes. Most of the effects of T on the male skeleton are mediated by
      its conversion to estradiol (E2) by the enzyme aromatase. Genetic variations in the aromatase
      (CYP19A1) gene result in enzymes with variable activity and variable levels of E2 and T. This
      project is designed to determine if genetic variations in the CYP19A1 gene will result in
      differences in the skeletal response and incidence of side effects from T treatment in
      patients with low T. A large number of male Veterans are on T. Results from this project will
      help identify patients who would benefit from the therapy from those at risk for side
      effects, and would definitely have an impact in the future care of these patients and male
      patients in general once genetic profiling becomes part of the standard of care.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male Veterans with low total testosterone (<300 ng/dl) as defined by the Endocrine
             Society, who are between 40-75 years of age.

          -  These patients must be ambulatory; and be willing and able to provide written informed
             consent.

        Exclusion Criteria:

          -  history of prostate cancer, breast cancer

          -  history of testicular disease

          -  untreated sleep apnea

          -  any ongoing illness that, in the opinion of the investigator, could prevent the
             subject from completing the study

          -  patients with a hematocrit of more than 50% (2010 Endocrine Society Guidelines)

          -  prostate-related findings of a palpable prostate nodule on exam, a serum PSA of 4.0
             ng/ml or more, International Prostate Symptom Score >8(9), urinary postvoid residual
             by ultrasound of >149 ml, or an abnormal transrectal ultrasound

          -  patients who are on androgen replacement therapy, selective androgen receptor
             modulator, or finasteride

          -  patients currently on medications that affects bone metabolism such as:

               -  estrogen

               -  the selective estrogen receptor modulator (SERM) as raloxifene

               -  use of bisphosphonates (i.e. risedronate, alendronate, zoledronic acid and
                  pamidronate)

               -  within two years of study entry

               -  aromatase inhibitors

               -  GnRH analogs

               -  glucocorticoids of at least 5 mg daily for one month or more

               -  anabolic steroids

               -  dilantin

               -  warfarin

          -  patients with diseases known to interfere with bone metabolism as hyperparathyroidism,
             untreated hyperthyroidism, osteomalacia, chronic liver disease, renal failure,
             hypercortisolism, malabsorption and immobilization

          -  those with current alcohol use of more than 3 drinks per day (62).

          -  history of documented coronary artery disease at high risk for recurrence

          -  Subjects with osteoporosis or a BMD T-score of -2.5 in the lumbar spine, total femur
             or femoral neck as well as those patients with a history of osteoporosis-related
             fractures (spine, hip or wrist) or vertebral deformities on lateral spine radiographs
             deemed as fragility fractures by the team principal investigator.

          -  history of documented coronary artery disease at high risk for recurrence, history of
             deep vein thrombosis and cerebrovascular event.