Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Placebo-Controlled, Double-Blind, Parallel Group Study With Open-Label Follow-up to Investigate the Effect of IM Testosterone Undecanoate on Biochemical and Anthropometric Characteristics of Metabolic Syndrome in Hypogonadal Men
Brief Summary: The objective of the study is to assess the effect of the testosterone therapy on the body composition, lipid and glucose metabolism, inflammatory markers in patients with metabolic syndrome and hypogonadism.


Options:
A: Inclusion Criteria:

* Age 60 years or greater
* Hypogonadism, Testosterone 100-400 ng/dl or Free Testosterone \< 50 pg/ml
* Generally good health
* At least 8 years of primary school education
* Able to pass screening test for dementia
* Able to give informed consent

Exclusion Criteria:

* Testosterone level \< 100 ng/dl (these individuals will be referred for evaluation of severe hypogonadism)
* Use of testosterone or other androgens \[dehydroepiandrosterone (DHEA), Androstenedione\] in last year
* Use of growth hormone in the last year
* Current alcohol of drug dependence \[Alcohol Use Disorders Identification Test (AUDIT) Score \> 8\]
* Diseases known to affect gonadal function
* Medications known to affect gonadal function eg. anticonvulsants, glucocorticoids such as prednisone
* Prostate cancer, breast cancer
* Any cancer that may limit life expectancy to less than 5 years
* Limiting neuromuscular, joint or bone disease
* History of stroke with residual neurologic deficit
* Neurologic condition that would impair cognitive function including:

epilepsy, multiple sclerosis, human immunodeficiency virus (HIV), Parkinson's disease, stroke

* Psychiatric disorder in the last year meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSMIV) Axis 1 criteria
* Use of psychotropic medicine for at least 6 months
* Dementia as assessed by (Telephone Interview for Cognitive Status modified score less than 31)
* Severe symptoms of benign prostatic hyperplasia (BPH) (American Urological Association symptom index score greater than 21)
* Prostate nodule or induration of digital rectal exam (DRE)
* Prostate specific antigen (PSA) greater than 4 unless participant has had a negative transrectal biopsy within last 3 months
* Limiting heart disease in including New York (NY) Class III or IV - congestive heart failure, unstable angina, or myocardial infarction (MI) in last 3 months
* Liver function tests \[aspartate aminotransferase (AST) and alanine aminotransferase(ALT)\] greater than 3 times the upper limit of the reference range
* Serum creatinine (Cr) greater than 2.5 mg/dl
* Hematocrit greater than 48%
* Hemoglobin (Hb)A1c greater than 9.0%
* Untreated thyroid disease
* Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg)
* Body mass index (BMI greater than 35 kg/m2)
* Untreated severe obstructive sleep apnea
* Development of electrocardiogram (EKG) changes consistent with myocardial ischemia or changes in blood pressure during cardiopulmonary exercise testing will be excluded from testing of muscle strength and physical function.
B: Inclusion Criteria:

* Men, 40-70 years of age, in a stable relationship, with mild to moderate erectile dysfunction for at least 6 months; defined as an IIEF-EF domain score between 11 and 25 (mild to moderate ED)
* Neutral or extremely dissatisfied with one's sex life
* Presence of androgen deficiency defined as serum total testosterone level less than 300 ng/dL (measured by LC-MS/MS) and/or free testosterone level (measured by equilibrium dialysis) less than 50 pg/ml.
* Able to understand the nature of the study and provide written, informed consent

Exclusion Criteria:

* Contraindication for use of testosterone, e.g., history of prostate or breast cancer
* benign prostatic hyperplasia with AUA/IPSS symptom scores of 21 or greater
* erythrocytosis (hematocrit \>50% at baseline)
* untreated, severe sleep apnea
* serum PSA levels \>4 ug/L will be excluded unless they have had a urologic evaluation in the past three months to exclude prostate cancer.
* Contraindication for use of sildenafil, e.g., symptomatic coronary artery disease taking long-acting or short-acting nitrate drugs on a regular basis.
* Symptomatic postural hypotension
* Congestive heart failure with class III or IV symptoms
* History of myocardial infarction or stroke within the past six months
* Primary diagnosis of another sexual disorder such as premature ejaculation
* AST, ALT, alkaline phosphatase elevation greater than three times the upper limit of normal, creatinine greater than 2 mg/dL.
* Currently taking testosterone or oral androgen precursors; unless willing to discontinue their use for 4 weeks (oral precursors or transdermal testosterone patch or gel) or 6 weeks (if injectable testosterone) before the initial screen visit.
* Currently taking medications that affect androgen metabolism, action, or clearance (dilantin, phenobarbital, aldactone, flutamide, finasteride).
* Uncontrolled diabetes mellitus or diabetes mellitus, e.g., if their baseline hemoglobin A1C is less than 8.5%.
* Structural abnormalities of the penis, including Peyronie's disease, will be excluded.
* Men who are taking medications for erectile dysfunction, including sildenafil, must stop using these medications for at least 4 weeks before starting Visit 2.
* DSM-IV criteria for an Axis I psychiatric disorder within the past year, including depression; use of psychotropic medication for at least six months, or dementia is also an exclusion.
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:

* A signed informed consent to participate in the study
* Men aged 35 to 70 with testosterone levels below 12 nmol/L or free testosterone below 225 pmol/L
* Presence of the metabolic syndrome according to the IDF definition

Exclusion Criteria:

* Patients under 35 or above 70 years.
* Participation in any clinical study within 30 days before the first injection of the drug
* Simultaneous participation in another clinical study
* Incapable subjects as well as prisoners
* Suspicion of a serious organic or mental disease according to medical history and/or clinical examination
* Prostate cancer, breast cancer or suspicion thereof
* Presence or history of hepatic tumors
* Acute or chronic hepatic disease
* Presence of renal diseases with renal failure
* Changes in biochemical or hematological laboratory values in spite of lack of clinical manifestations, in the investigator's opinion
* Suspected lack of the patient's compliance
* Hypersensitivity to the active substance

Answer: D