Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Placebo-controlled, Double-blind Study of Seven Coordinated Testosterone Treatment Trials in Older Men
Brief Summary: The Testosterone Trials are a multi-center set of trials involving 12 clinical sites geographically distributed across the United States.

The primary specific aims are to test the hypotheses that testosterone treatment of elderly men whose serum testosterone concentrations are unequivocally low - and who have symptoms and objectively measured abnormalities in at least one of five areas that could be due to low testosterone (physical or sexual function, vitality, cognition, and anemia) - will result in more favorable changes in those abnormalities than placebo treatment.

Two additional trials have been incorporated into the T Trial. Only men enrolled in the T Trial are eligible to participate in these trials.

* The Cardiovascular Trial will examine if testosterone treatment results in more favorable changes in cardiovascular risk factors, compared to placebo.
* The Bone Trial will test the hypothesis that testosterone treatment will increase volumetric trabecular bone mineral density (vBMD) of the lumbar spine as measured by quantitative computed tomography (QCT), compared with placebo treatment.

A Pharmacokinetic (PK) Study is also being conducted within the context of the interventional T Trial. It will examine the variability of the serum testosterone (T) concentration after application of testosterone gel or placebo, four months after the start of treatment.


Options:
A: Inclusion Criteria:

* Serum testosterone of less than or equal to 300 ng/dL on two occasions within one week (may wash out from previous oral, topical or buccal testosterone therapy)

Exclusion Criteria:

* Significant intercurrent disease of any type, in particular liver, kidney, uncontrolled or poorly controlled heart disease, or psychiatric illness
* Recent history of stroke, not including transient ischemic attack
* Untreated, sever obstructive sleep apnea.
* Hematocrit \<35% or \>48
* Serum transaminases \>2 times upper limit of normal, serum bilirubin \> 2.0 mg/dL and serum creatinine \> 2.0 mgk/dL
* BMI \> or equal to 36
* Stable doses of lipid-lowering medication for less than 3 months
* Stable doses of oral medication for diabetes for less than 2 months
* Abnormal prostate DRE \[palpable nodule(s)\], elevated PSA (\>4 ng/mL), IPSS score \> or equal to 19 points.
* History of breast cancer
* Use of dietary supplement saw palmetto or phytoestrogens and use of any dietary supplements that may increase serum testosterone within previous 4 weeks
* Known malabsorption syndrome and/or current treatment with oral lipase inhibitors
* History of abuse of alcohol or any drug substance within the previous 2 years
* Current use of antiandrogens, estrogens, oral CYP3A4 inducers or inhibitors, or long-acting opioid analgesics
* Receipt of any drug as part of a research study within 30 days of initial dose administration in this study.
* Blood donation within the 12 week period before the initial study dose.
B: Inclusion Criteria:

* Men between 45 and 80 years age
* Participants with low serum testosterone concentrations (\< 300 ng/dL) who exhibit at least one sign or symptom of hypogonadism and have evidence of cardiovascular (CV) disease or are at an increased risk for CV disease.

Exclusion Criteria:

* Participants with congenital or acquired hypogonadism for whom long-term therapy with placebo would not be medically appropriate
* Participants with prostate specific antigen (PSA) \> 3.0 ng/mL (or 1.5 if on 5-alpha reductase inhibitors)
* Participants who have been treated with testosterone in the past 6 months and for whom testosterone therapy is contraindicated
* Confirmed testosterone \< 100 ng/dL
* Body Mass Index (BMI) \> 50
* Hemoglobin A1c (HbA1C) \> 11%
* Hematocrit (Hct) \> 50%
* Estimated Glomerular Filtration Rate (eGFR) \< 30 ml/min
* History of deep vein thrombosis or pulmonary embolism or prostate cancer or heart failure (Class III and IV).
C: 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)
D: 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.

Answer: D