Please select the eligibility criteria that correspond to the clinical trial below.
Title: Testosterone Replacement to Augment Lifestyle Therapy in Obese Older Veterans
Brief Summary: The prevalence of obesity in Veterans is greater than in the general population, and even more so among users of the VA Health Care System. In addition, the population of obese older Veterans is rapidly increasing as more baby boomers become senior citizens. In older Veterans, obesity exacerbates the age- related decline in physical function and causes frailty which predisposes to admission to a VA chronic care facility. However, the optimal clinical approach to obesity in older adults is controversial because of the concern that weight loss therapy could be harmful by aggravating the age-related loss of muscle mass and bone mass. In fact, the MOVE (Managing Overweight/Obese Veterans) program does not have any guidelines for eligible Veterans if they are 70 or older. It is possible that the addition of testosterone replacement to lifestyle therapy will preserve muscle mass and bone mass and reverse frailty in obese older Veterans and thus prevent their loss of independence and decrease demand for VA health care services.


Options:
A: Inclusion Criteria:

* Men greater than or equal to 65 years old
* Total serum testosterone concentration \< 275 and \< 300 ng/dL at 7 -10 AM at each of two screening visits

Exclusion Criteria:

* Diagnosed prostate cancer, prostatic intraepithelial neoplasia (PIN), prostate nodule or, by the Prostate Cancer Risk Calculator, a \>35% risk of having overall prostate cancer or \>7% risk of having high grade prostate cancer
* Severe lower urinary tract symptoms (score of \> 19) by the International Prostate Symptom Score questionnaire
* Hemoglobin \<10 g/dL or \>16.0 g/dL
* Sleep apnea, diagnosed but untreated
* Alcohol or substance abuse within the past year (based on self report)
* Angina not controlled by treatment
* NYHA class III or IV congestive heart failure
* Myocardial infarction within the previous 3 months before entry
* Stroke within the previous 3 months before entry
* Severe pulmonary disease that precludes physical function tests
* Serum creatinine \>2.2 mg/dL; ALT 3x upper limit of normal; hemoglobin A1c \>8.5%, TSH \> 7.5mIU/L
* Diagnosis or treatment for cancer within the past 3 years, with the exception of nonmelanotic skin cancer
* Body mass index (BMI) \>37 kg/m2
* Mini Mental State Exam (MMSE) Score \<24
* Major psychiatric disorders, including major depression (PHQ-9 score \> 14), mania, hypomania, psychosis, schizophrenia or schizoaffective disorders, that are untreated, unstable, have resulted in hospitalization or medication change within the previous three months, or would result in inability to complete the trial efficacy instruments. Subjects whose disorders have been stable while being treated for more than three months are eligible.
* Use of the following medications within the previous three months:

  * drugs that affect serum testosterone concentration
  * rhGH or megestrol acetate
  * introduction of anti-depressant medication
  * daily use of prednisone for more than two weeks
* Opiate use within the past three months
* Skin conditions at the testosterone gel application site, such as ulcer, erosion, lichenification, inflammation, or crust, or generalized skin conditions such as psoriasis or eczema that might affect testosterone absorption or tolerability of the testosterone gel
* Known skin intolerance to alcohol or allergy to any of the ingredients of testosterone gel

Participants in the T Trial may also enroll in the Cardiovascular and Bone Trials if it is determined that they are eligible based on the specific exclusion criteria.
B: Inclusion Criteria:

* Male gender age 50-70
* Bioavailable testosterone \< 7,3 nmol/L
* Metformin treatment of T2DM for 3 months or more

Exclusion Criteria:

* HbA1c \> 9,0 %, BMI \> 40 kg/m2, Haematocrit \> 50%,
* Known malignant disease, PSA \> 3 ug/L, Nycturia \> 3 times,
* Abnormal routine blood samples,
* Severe hypertension,
* Significant EKG-changes,
* Wish of parenthood,
* Active mental illness,
* former or present abuse,
* Severe illness of heart-, lung- or kidney,
* Primary or secondary hypogonadism.
C: Inclusion Criteria:

* Subjects were at least 50 years of age
* A body mass index (BMI) between 18 and 34 kg/m\^2
* Symptoms of androgen deficiency (as indicated by a positive Androgen Deficiency in Aging Males (ADAM) questionnaire)
* Calculated free testosterone measurement of \<0.26 nmol/L in the morning

Exclusion Criteria:

* History or current diagnosis of breast or prostate cancer
* any clinically significant abnormal finding on physical examination including the prostate
* Clinical symptoms of obstructive benign prostate hyperplasia (International Prostate Symptom Score (IPSS) \>14)
* Prostate specific antigen (PSA) level \> 4 ng/mL at screening
* Cause of androgen deficiency other than aging, e.g. 'classical' diagnosis of primary or secondary hypogonadism
* Hyperprolactinaemia or treatment with prolactin-lowering drugs
* History of known chronic polycythemia and/or hematocrit \>50% at screening
* History or presence of severe sleep apnea
* Unstable or untreated endocrine disorders
* History or presence of clinically significant depression or other psychiatric disorder or any clinically relevant cardiovascular, cerebrovascular, endocrine, hepatic, renal or hematological disease, thromboembolism/thrombosis etc. which, in the opinion of the investigator, might compromise the subject's participation in the trial
* Use of medication that would interfere with the efficacy and safety objectives of the trial
D: Inclusion Criteria:

Subjects will be

* older (65-85 yr)
* obese (BMI 30 kg/m2 or greater) Veteran men with low testosterone (less than 300 mg/dL) as defined by the Endocrine Society
* mild to moderately frail
* must have stable weight (\~not less than or more than 2 kg) during the last 6 months
* sedentary (regular exercise less than 1 h/week or less than 2x/week for the last 6 months)

Exclusion Criteria:

* Any major chronic diseases, or any condition that would interfere with exercise or dietary restriction, in which exercise or dietary restriction are contraindicated, or that would interfere with interpretation of results.
* Examples include, but are not limited to:

  * cardiopulmonary disease (e.g. recent myocardial infarction (MI), unstable angina, stroke etc) or unstable disease (e.g. CHF)
  * severe orthopedic/musculoskeletal or neuromuscular impairments
  * visual or hearing impairments
  * cognitive impairment (Mini Mental State Exam Score less than 24)
  * current use of bone active drugs
  * uncontrolled diabetes (i.e. fasting blood glucose more than 140 mg/dl and/or HbA1c greater than 9.5%).
* Any contraindications to testosterone supplementation

  * history of prostate or breast cancer
  * history of testicular disease
  * untreated sleep apnea
  * hematocrit more than 50%
  * prostate-related findings of palpable nodule on exam, a serum PSA of 4.0 ng/ml or greater
  * International Prostate Symptom Sore more than 19
  * history of venous thromboembolism
* Osteoporosis or a BMD T-score of -2.5 in the lumbar spine or total hip as well as those patients with a history of osteoporosis-related fracture (spine, hip, or wrist)

Answer: D