The Prostate Gland and BPH
BPH Definition
These recommendations are from the American Urological Association (AUA) Guidelines on the Management of Benign Prostatic Hyperplasia (BPH): Diagnosis and Treatment Recommendations and are presented in abbreviated form. Readers should refer to the full guideline document1 for more detailed information.
Benign prostatic hyperplasia is a progressive disease defined histologically and characterized by stromal and epithelial cell hyperplasia beginning in the periurethral zone of the prostate.2,3 The chief complaint of the patient with BPH is usually bothersome LUTS typified by urinary frequency, urgency, nocturia, decreased and intermittent force of stream and the sensation of incomplete bladder emptying.
BPH is often associated with enlargement of the prostate (BPE) .However the relationship between BPH ,LUTs and BPE is complex and not all patients with BPH will have LUTS or BPE and also (BPE) may exist in the absence of LUTS.
BPH is one of the most common conditions affecting older men and can cause major disruption in everyday life (Marks et al 2006).
Schematic longitudinal sections showing development of BPH
BPH Etiology
The aetiology of BPH is not completely understood, but advancing age and testicular androgens play a central role.2-4 The age-related enlargement of the prostate seen in men with BPH may be caused by increased cellular proliferation combined with a decreased rate of apoptosis (programmed cell death). Other factors that may contribute to BPH are the effects of oestrogens, interactions between prostatic stromal and epithelial tissues, growth factors in the prostate gland, and neurotransmitters released in the gland. These factors may act alone or in combination to promote the development of BPH.
The importance of DHT and the two 5 alfa reductase isoenzymes
DHT is the primary prostatic androgen responsible for cell growth and proliferation, and for facilitation of cell atrophy and apoptosis. The enzyme 5a-reductase, which exists in two distinct isoforms - type 1 and type 2, converts testosterone into DHT.
Conversion of testosterone to dihydrotestosterone
The type 2 isoenzyme is located primarily in stromal tissue of the prostate, and is critical for the normal development of the prostate; it is also involved in the development of BPH.
The type 1 isoenzyme converts testosterone into DHT in peripheral tissues such as the skin and liver, but is also present in the prostate, in lower concentrations than the type 2 isoenzyme.
There is evidence to indicate that DHT is a causative factor in the development of BPH. Most importantly, BPH does not develop in men castrated before puberty, and prostate growth is significantly impaired in patients with a variety of genetic diseases that inhibit androgen-androgen production or androgen action (e.g. a type 2, 5a-reductase deficiency).5 Furthermore, levels of intraprostatic DHT are not elevated in men with BPH, and remain normal despite the fact that circulating testosterone levels decline with ageing. Additionally, the androgen receptors are down-regulated in many androgen responsive organs after puberty, but this down-regulation does not occur in the ageing prostate. Thus, DHT-dependent growth can continue, despite the age-related declines in plasma testosterone.
Additional References:
1. AUA Guidelines on the Management of Benign Prostatic Hyperplasia (BPH): Diagnosis and Treatment Recommendations. Available from URL: http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=bph Accessed: February 2007.
2. Lee, C., Cockett, A., Cussenot, K., Griffiths, K., Isaacs, W., and Schalken. “Regulation of Prostate Growth”. In: Proceedings of the Fifth International Consultation on BenignProstatic Hyperplasia. Edited by C. Chatelain, L. Denis, K.T. Foo, S. Khoury, and J. McConnell. United Kingdom: Health Publications Ltd., chapt. 3, 79-106, 2001.
3. McNeal, J. E. Origin and evolution of benign prostatic enlargement. Invest Urol, 15: 340, 1978.