Assessment of systemic effects of sex hormone alterations in androgen deprivation therapy for prostate cancer

Abstract

Sex hormonal variations cause bodily changes reflecting their systemic functions. This project was designed to define the influence of sex hormones on systemic function in men with prostate cancer (PC) receiving contemporary androgen deprivation therapy (ADT) with luteinising hormone-releasing hormone agonists (LHRHa). LHRHa induced suppression of sex hormones results in multiple serious toxicities of which the cognitive, skeletal and psychosocial aspects were addressed in this project. Acute castration appears to cause cognitive problems in some men with PC. In order to identify the neuropathology of such cognitive decline, positron emission tomography (PET) was used along with a battery of validated neuropsychological tests, documenting for the first time an increased global and regional cortical neuroinflammatory response in patients with PC experiencing cognitive deterioration since being on LHRHa. Bone mineral density, a commonly employed measure of bone mass, lacks accuracy in predicting bone strength and fracture risk. The present work showed bone volume fraction (a newer non-invasive metric of bone mass derived using computed tomography imaging) to be highly correlated with bone strength measured ex-vivo, thereby demonstrating its potential for use in clinical assessments. Levels of serum bone-specific alkaline phosphatase, a marker of skeletal metabolism, were also measured to assess bone changes in the early stages of LHRHa therapy but no change was observed. Metabolic derivatives of sex hormones have been suggested to influence psycho-socio-sexual behaviour via odour signalling. The current work, investigating effects of castration on odour, showed no change in the olfactory perception of odour samples provided by men on LHRHa treatment. These pilot data and observations will help shape future work that may not only improve quality of life outcomes in men with PC undergoing ADT but also benefit patients suffering from other clinical conditions involving physiological, pathological or therapeutic changes in sex hormone levels.