INTRODUCTION AND OBJECTIVES: Replacement therapy with testosterone (T) is recognized as an effective treatment for patients with symptoms and signs of hypogonadism. Yet concerns remain regarding the potential for increased T to stimulate prostate cancer (PCa), particularly for long-acting T preparations. The aim of this study was to evaluate the effect of long-acting T undecanoate injections in patients with PCa treated with brachytherapy. METHODS: Since February 2005, 116 patients with PCa have been treated with brachytherapy by one urologist. Since 2008, has been incorporated into our protocol to measure total T and free T in patients with symptoms of hypogonadism (low libido, erectile dysfunction and fatigue). In total, 16 patients have hormonal study and follow-up after receiving T replacement using long-acting T undecanoate injections (starting with 1.000mg intramuscular injections every 4 weeks and then according to total T and free T serum levels). All patients were follow monthly with PSA and serum T levels for three months, then every 3 months the first year, every 6 months the second year and annually then after. RESULTS: Mean age of 16 patients was 62 years (i:49–74). Mean PSA at diagnosis was 6.2 ng/ml (i:2–11.5). The Gleason score was 2 3 in 1 patient, 3 3 in 12 patients, 3 4 in 2 patients and 4 4 in 1 patient. With respect to clinical stage, 11 patients had stage T1c and 5 T2a. All patients had symptoms. Mean total T was 343ng/dl (i:200– 592) (normal range: 280–1000) and free T of 6.9 ng/dl (i:2.1–9.7) (normal range: 11.7–18.5). All patients received replacement with long-acting T undecanoate injections and all of them had improvement in their symptoms of hypogonadism and erectile function, as assessed by SHIM score (mean of 16.1 post-brachytherapy and mean of 22.1 after treatment with long-acting T undecanoate injections; p 0.002). The PSA showed no significant variation after starting therapy with T (mean PSA of 0.65ng/ml at baseline and 0.55ng/ml at follow-up; p 0.44). No patients showed progression by PSA, with a median followup of 9 months (i:3–24). CONCLUSIONS: In this small group of patients with PCa treated with brachytherapy, replacement therapy with long-acting T injections had a positive impact on the symptoms of hypogonadism and erectile function, without short-term PSA progression.