Testosterone Replacement in Male Cancer Survivors with Fatigue and Low Testosterone

Inclusion Criteria:

• Cancer survivors who have received chemotherapy and/or radiation therapy for theircancer and are now in remission for at least one year

• Non-hormone-dependent cancer, including most solid tumors, lymphomas and leukemias

• Age: 18-54 years

• Serum testosterone, measured by mass spectrometry (gold standard method), of <348ng/dl and/or free testosterone <70 pg/ml. The lower limits of the normal range fortotal testosterone in healthy young men (age 19-40 years), is 348 ng/dL and thelower limits of free testosterone is <70 pg/ml in the Framingham Heart Studysample97. Therefore, young symptomatic men with total testosterone <348 ng/dl couldbe considered testosterone deficient. As sex hormone binding globulin levels may beelevated in some men with cancer (resulting in elevation in total testosteronelevel), some of these symptomatic men may still be hypogonadal despite having totaltestosterone above this cut-off limit. However; their free testosterone levels maystill be below the lower limit of normal. Thus, we will also include men with freetestosterone <70 pg/mL.

• Self-reported fatigue. We have selected these symptoms because they are commonlyreported in male cancer survivors. Fatigue will be defined as a score on FunctionalAssessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale of <40, which bestdivides cancer patients from the general population with 84% accuracy, and was usedas the cut-off for the NIA-funded 50-million-dollar testosterone trial (TheT-Trial).

• Ability and willingness to provide informed consent.

Exclusion Criteria:

• Men with hormone-dependent cancers (breast, prostate or adenocarcinoma of unknownorigin)

• Men with brain cancer (potential cognitive impairment)

• Use of anabolic agents (testosterone, dehydroepiandrosterone, growth hormone) withinthe past 6 months

• Appetite stimulating agents e.g. megestrol acetate within the past 6 months

• Systemic glucocorticoids e.g. prednisone 20 mg daily or equivalent doses of otherglucocorticoids for more than two weeks in the past 6 months

• Baseline hematocrit >48%

• PSA >4 ng/ml in Caucasians; >3 ng/ml in African-Americans

• Men with 1st order relatives with a history of prostate cancer

• Uncontrolled congestive heart failure

• Severe untreated sleep apnea

• Myocardial infarction, acute coronary syndrome, revascularization surgery, or strokewithin 3 months o Previous stroke with residual cognitive or functional deficits; Mini-Mental StateExamination score <24

• Serum creatinine >2.5 mg/dL; ALT 3x upper limit of normal

• Poorly controlled diabetes as defined by hemoglobin A1c >8.5%; Body mass index (BMI) >45 kg/m2

• Untreated unipolar depression (treated depression with medications or counselingwill be allowed

• Bipolar disorder or schizophrenia