Improving Quality of Life of Prostate Cancer Survivors With Androgen Deficiency

The overall objective is to conduct a proof-of-concept double-blind, placebo-controlled,
parallel group, randomized trial to determine the efficacy and safety of testosterone
replacement therapy(TRT) in improving the symptoms of androgen deficiency (sexual symptoms,
low energy, and physical dysfunction) and overall health-related quality of life in men with
prostate cancer who have undergone radical prostatectomy for organ-localized disease
(pT2,N0,M0), Gleason score < 6 (no Gleason 4 elements), who have undetectable PSA (<0.1 ng/mL
using a sensitive PSA assay) for > 2 years after radical prostatectomy, and who have androgen
deficiency.

Inclusion Criteria:

Men with prostate cancer, who have Stage pT2, N0, M0 lesions (confined to the gland);
Combined Gleason score of 6 or less with no Gleason 4 elements; Preoperative PSA less than
10 ng/ml; 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, fatigue/low vitality, or physical
dysfunction.

- An average of two fasting, early morning serum testosterone levels, measured by
LC-MS/MS, less than 275 mg/dL and/or free testosterone by equilibrium dialysis <60
pg/mL. middle-aged and older men with mean testosterone levels > 300 ng/dL.

- Ability and willingness to provide informed consent

Exclusion Criteria:

- Men who have undergone radiation therapy

- 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; ALT 3x upper limit of normal;

- Hemoglobin A1c >7.5% or diabetes requiring insulin therapy

- Body mass index (BMI) >40 kg/m2

- Untreated depression. Subjects with depression who have been on stable anti-depressant
medication for more than three months are eligible.

- Men with axis I psychiatric disorder, such as schizophrenia, will be excluded.

- Subjects who have used the following medications within the past 6 months:
testosterone, DHEA, estrogens, GnRH analogs, antiandrogens, spironolactone,
ketoconazole, rhGH, megestrol acetate, prednisone 20 mg daily or equivalent doses of
other glucocorticoids for more than two weeks