Nima Sharifi and Charles J Ryan
Nima Sharifi, James L Gulley and William L Dahut
Androgen deprivation therapy (ADT) with gonadal testosterone depletion is the frontline treatment for advanced prostate cancer. Other hormonal interventions have a role in the treatment of prostate cancer. We sought to examine systematically the evidence for hormonal interventions in prostate cancer, risks of ADT, and interventions that mitigate these risks. Search results for therapeutic studies were focused primarily on randomized controlled clinical trials, and the Jadad scale criteria were used to evaluate the quality of these studies. Four trials of the efficacy of intermittent ADT versus continuous ADT were included. One randomized study analysis and six postrandomization analyses were included on the effects of ADT on cardiovascular mortality. Seven randomized controlled trials of pharmacologic interventions were included for the treatment of metabolic effects due to ADT. One randomized trial of GnRH antagonist versus GnRH agonist was included. Six phase I/II clinical trials of secondary hormonal therapies with novel mechanisms of action were included. Randomized studies completed to date indicate that intermittent ADT might be equivalent to continuous ADT. Although adverse effects of ADT include risk factors for cardiovascular disease, effects on cardiovascular mortality are uncertain. Bone loss and increased risk of fracture may be effectively treated with pharmacologic interventions. Benefits of ADT must be balanced with a consideration of the risks.