Andrology Projects

Androgens and the Prostate

• Origins of Prostate Disease
• Dihydrotestosterone (DHT) Efficacy and Safety Study - for details link here
• Tissue-selective Role of Androgens in the Prostate - for details link here
  

• Origins of Prostate Disease

K Griffiths, G Sartorious, B Jin, L Chan, A Conway, DJ Handelsman

Our clinical studies on the origins of prostate disease have also focussed on early life factors (such as pre-birth or during puberty) that may predestine the development of prostate disease decades later.

We are undertaking two long-term clinical cohort studies. In one, we are following a cohort of 570 men studied 5-10 years previously to measure the growth rate of the human prostate by ultrasound and to identify lifestyle, hormonal and genetic factors that may influence it. In the second study, we are focussing on how events before and soon after birth may determine the susceptibility of the prostate to diseases such as prostate cancer and hyperplasia in later life. In this project, we are establishing a birth cohort of young men born ~1970 in inner Sydney and who are now in their early 30’s. The latter study requires us to trace young men born in Sydney around 1970 using hospital birth records. In contrast to a birth cohort of girls developed by collaborators in Adelaide, the recruitment of boys in Sydney has proved to be much more difficult, due, at least in part, to the requirement for an invasive transrectal ultrasound. As a response, we developed and validated a new less invasive method, transperineal ultrasound, which we showed to be as reliable as the standard transrectal methods. This new method published in the top Urology journal should facilitate future population studies of healthy men prior to onset of overt prostate disease.

• Dihydrotestosterone (DHT) Efficacy and Safety Study

A Idan, K Griffiths, L Turner, AJ Conway, D J Handelsman

A major research project has been completed to evaluate whether DHT is effective in preventing prostate growth in middle-aged men without known prostate disease. It also aims to determine DHT treatment has any adverse effects on bone or the cardiovascular system. This study is also provides unique foresight into the likely benefits and risks of the new class of pure androgens, known as SARMs, for which DHT is the prototype. This randomised, double blind placebo controlled study is investigator-initiated and sponsored by an overseas pharmaceutical company. Our findings show that prostate growth was not influenced by the daily topical administration of DHT over a 2 year period and overall had a variety of expected benefits and remained relatively safe to use. The results have been presented to the US and Australian Endocrine Societies and a manuscript for a major international journal is in preparation.
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• Tissue-selective Role of Androgens in the Prostate

U Simanainen, K McNamara, E Gao, CM Allan, DJ Handelsman

The androgen receptor (AR) has a crucial role in both normal prostate development and the emergence and progression of prostate cancer. Ulla Simanainen (PhD, Finland) has joined the laboratory to study the AR and prostate function by applying innovative transgenic approaches to selectively disrupt AR function in defined cell types within the mouse prostate. We have created a model targeting AR in the prostate epithelium to explore the role of androgen in the development of structures fundamental to normal functioning prostate, as well as in prostate proliferative diseases of benign prostate hyperplasia and cancer that develop in later life. Our ongoing research will also investigate the influence of selective AR deprivation on long-term steroidal sensitivity of the prostate, noting that early hormonal exposure and deprivation may have long-range influences and essential roles in the subsequent development of prostate cancer later in life. Our research may provide new clues for targets for prevention, screening and/or treatment for prostate diseases including prostate cancer.
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