BACKGROUND: Androgen deprivation therapy (ADT) is the standard care in men with advanced prostate cancer. Continuous testosterone suppression is essential to treatment efficacy. Recently a 1 year depot compound, histrelin, (VANTAS: Orion Pharmaceuticals, Finland; Endo Pharmaceuticals, USA), a gonadotropin-releasing hormone (GnRH) analog, was approved for hormone therapy of prostate cancer. In the present study the therapeutic efficacy of this compound was investigated, in addition to its impact on testosterone values and velocity as well as PSA. METHOD: One hundred thirty-one patients with histologically confirmed prostate cancer and normal testosterone levels were prospectively evaluated over 1 year. Androgen deprivation therapy was performed using a once yearly implant of the GnRH agonist histrelin. Testosterone and PSA levels, and histrelin serum profile were measured prospectively every month for 1 year. In addition, patients were stratified according to their PSA results and D'Amico risk profile. RESULTS: Testosterone suppression (testosterone < or = 50 ng/dL) was measured in all patients between weeks 4 and 52; 88% of patients had a continuous testosterone level under 20 ng/dL. The PSA level in the total population decreased significantly within the first 2 weeks compared with baseline, and after 52 weeks the median PSA level of the total population was 0.2 ng/mL. PSA responses were grouped into three typical therapeutic outcomes and correlated with the clinical risk distribution, and levels were lowered in all three risk groups. CONCLUSION: The GnRH agonist histrelin successfully suppressed testosterone over the entire study period. This effect was measured across a number of different clinical definitions of PSA response and clinical risk. The GnRH agonist therefore offers an effective therapy option in hormone treatment of prostate cancer.