Testosterone Replacement Therapy in Improving Quality of Life in Prostate Cancer Survivors with Androgen Deficiency

Inclusion Criteria

• The rationale for selecting men with the following criteria is that this group of men has less than 0.1% disease recurrence rate over ten years. Therefore, we will enroll men with prostate cancer, who have: * Stage pT2, N0, M0 lesions (confined to the gland if American Joint Committee on Cancer [AJCC] staging is not available in medical records, the investigators will infer the staging based on extensive review of the pathology report) * Combined Gleason score of 7 (3+4) or less * Preoperative PSA less than 10 ng/mL (if pre-operative PSA is not available in medical records, low-risk subjects with a Gleason score of 6 [3+3] and who are at least 5 years out of surgery will be considered for enrollment) or (If preoperative PSA is 10.1 ng/mL to 20 ng/mL, the study physicians will thoroughly review all available medical documentation specifically including operative pathology report, years free of recurrence after prostatectomy, current PSA and post-operative PSA history, and communication with subject’s treating physician to fully asset risk of prostate cancer reoccurrence) * Stable and undetectable PSA level (PSA less than 0.1 ng/mL using an assay that has a functional sensitivity of =< 0.1 ng/mL) for at least two years after radical prostatectomy.
• Age: 40 years and older.
• Presence of symptoms related to sexual dysfunction, or fatigue/low vitality, or physical dysfunction. We have selected these symptoms because they are commonly reported by men treated for prostate cancer and likely to respond to testosterone replacement. Sexual dysfunction will be operationalized as the presence of low libido and/ or erectile dysfunction. The diagnosis of erectile dysfunction will be established by using the International Index of Erectile Dysfunction (IIEF). Men with IIEF scores < 25 will be selected. Low libido will be assessed using the DeRogatis Inventory of Sexual Function Sexual Desire domain score =< 20, as was done in the National Institute on Aging (NIA)-funded T (testosterone) trials. Fatigue/low vitality will be defined as a score on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale of < 30, which is one standard deviation (SD) below the mean for men > 65 years (FACIT Fatigue manual) and captures > 75% of cancer patients with symptomatic anemia.
• An average of two fasting, early morning serum testosterone levels, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), less than 275 ng/dL if the first total testosterone value in a subject is > 500 ng/dl, that subject would not require a second total testosterone draw as it is unlikely for the average value to fall below 275 ng/dL) and/or a single free testosterone by equilibrium dialysis =< 70 pg/mL(if the free testosterone concentrations are < 70 pg/ml, then the subject will be considered qualified and a 2nd total testosterone measurement would not be required). These testosterone thresholds are based on the results of the TTrials, which demonstrated that testosterone replacement of men with total testosterone less than 275 ng/dL and low libido was associated with significant improvements in libido, erectile function, overall sexual activity, and satisfaction with erections. Similarly, in an efficacy trial of testosterone solution in hypogonadal men with baseline total testosterone less than 300 ng/dL, testosterone replacement therapy was associated with significantly greater improvements in sexual drive and erections in hypogonadal men with low libido, and significantly greater improvements in energy level in men with low energy. In contrast, testosterone administration did not significantly improve any domain of sexual function in middle-aged and older men with mean testosterone levels > 300 ng/dL. We recognize that sex hormone-binding globulin (SHBG) levels are higher in older men; therefore, some older men with total testosterone levels greater than the upper limit of normal may have free testosterone levels that are below the lower limit of normal for healthy, young men. Thus, we would include men with free testosterone level below =< 70 pg/mL (lower limit of normal in follicle-stimulating hormone [FHS] < 69 pg/mL).
• Willingness to not make any major changes in dietary intake and to maintain current exercise activities and avoid any new exercise programs.
• Ability and willingness to provide informed consent.

Exclusion Criteria

• Men who have undergone radiation therapy alone will be excluded because defining biochemical recurrence can be difficult in these men because of fluctuating PSA levels. Men who have received adjuvant radiation therapy after prostatectomy and men who have received salvage radiation therapy after prostatectomy would also be excluded.
• Men receiving androgen deprivation therapy will be excluded.
• Hemoglobin < 10 g/dL or > 16.5 g/dL.
• Severe untreated sleep apnea.
• Uncontrolled heart failure.
• Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within 3 months.
• Serum creatinine > 2.5 mg/dL
• Alanine aminotransferase (ALT) 3 x upper limit of normal.
• Glycosylated hemoglobin (hemoglobin A1c) > 7.5% or diabetes requiring insulin therapy.
• Body mass index (BMI) > 40 kg/m^2.
• Untreated depression. Subjects with depression who have been on stable anti-depressant medication or undergoing cognitive behavioral therapy for more than three months are eligible.
• Men with uncontrolled axis I psychiatric disorder, such as schizophrenia, will be excluded.
• Subjects who have used the following medications within the past 6 months: testosterone, dehydroepiandrosterone (DHEA), estrogens, gonadotropin-releasing hormone (GnRH) analogs, antiandrogens, spironolactone usage greater than 200 mg daily, ketoconazole, rhGH, megestrol acetate, prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks.