Adverse Effects of Androgen Deprivation Therapy for Prostate Cancer: Prevention and Management

The prostate is an androgen-dependent organ. The increase, growth, homeostasis, and function of the prostate largely depend upon the intraprostatic and serum concentrations of androgens. Therefore, androgens are essential for the physiologic growth of prostatic epithelium. Prostate cancer, the second leading cause of death for men, is also androgen dependent, and androgen suppression is the mainstay of treatment for advanced and metastatic disease. In the state of metastatic disease, androgen suppression is a palliative treatment leading to a median progression-free survival of 18–20 months and an overall survival of 24–36 months. Theoretically, the majority of patients will develop hormone-refractory disease provided that they will not die from other causes. Although androgen suppression therapy may be associated with significant and sometimes durable responses, it is not considered a cure, and its potential efficacy is further limited by an array of significant and bothersome adverse effects caused by the suppression of androgens. These effects have potentially significant consequences on a variety of parameters of everyday living and may further decrease health-related quality of life. This review focuses on the aetiology of these adverse effects and provides information on their prevention and management. 1. Introduction It is estimated that there are nearly 2.8 million men living with a history of prostate cancer in the USA, and an additional 241,740 cases will be diagnosed in 2012 [1]. Androgen deprivation therapy (ADT) is undoubtedly the mainstay of treatment for symptomatic metastatic prostate cancer. Although ADT indications are limited to the palliation of symptomatic metastases, ADT is widely used in men with biochemical (PSA) relapse after radical prostatectomy, locally advanced disease, lymph node metastases, and also asymptomatic metastatic disease [2, 3]. ADT is also commonly used in combination with external beam radiotherapy (EBRT) for intermediate to high-risk prostate cancer cases in order to improve responses to radiotherapy [4]. In total, it is estimated that approximately 40% of patients diagnosed with prostate cancer will receive ADT within 6 months of diagnosis [5]. Although there is no doubt that ADT is efficacious in delaying disease progression and alleviating symptoms from metastatic disease, ADT is associated with multiple and significant side effects. Given this, it is considerate to assign patients to ADT only when this is necessary and delay its implementation in order to spare the patients some of the associated