Grant R21CA171316

Hypogonadism and Pain Perception in Androgen-Deprived Men with Prostate Cancer

DESCRIPTION (provided by applicant): The overall goal of this proposal is to evaluate the change in clinical and experimental pain in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT) and compare them with men with PCa not receiving ADT (non-ADT). The use of ADT is associated with a significant decrease in quality of life (QOL).This decrease is evident in both physical and mental composites of SF-36 QOL questionnaire. One of the aspects of the physical composite is the perception of pain. Preliminary cross-sectional studies have shown that men undergoing ADT report more clinical pain when compared with men in the non-ADT group and with age-matched healthy controls. As this increased pain perception is seen even in those androgen-deprived men without any metastatic disease, these findings implicate profound hypogonadism as the main etiology for these symptoms. Male hypogonadism is an inflammatory state associated with an increase in pro-inflammatory cytokines like IL-6 and TNF-[unreadable], both of which have been associated with clinical and experimental pain. Androgen deprivation therapy is also associated with metabolic abnormalities such as insulin resistance and hyperglycemia. Hence, it is unclear whether the increased prevalence/severity of pain in men on ADT is due to direct effects of hypogonadism or secondary to these metabolic abnormalities. We propose a prospective study in which: 1) we will compare changes in clinical pain reports and psychophysical pain responses between men undergoing ADT vs. non-ADT over a 6-month time period, and 2) We will assess the associations of various metabolic and inflammatory markers with pain perception and pain threshold in men undergoing ADT. The proposed study, in addition to advancing our understanding of the mechanism of pain development in men on ADT, is likely to have a significant clinical impact on the overall health-management of patients on ADT. The results of this study will guide physicians to use ADT for appropriate indications and to screen these patients for incident pain during ADT. Since androgen replacement is contraindicated in men with PCa, this study will lay the groundwork for prospective trials assessing the role of novel anti-inflammatory agents, insulin- sensitizing agents or SARMS (selective androgen receptor modulators) in the prevention and treatment of pain during ADT.