The pathophysiology of benign prostatic hyperplasia is a complex process that is not yet fully understood. However, it is widely accepted that the development of BPH is multifactorial, involving hormonal dysregulation, cellular growth and proliferation, and the effects of aging. The central mechanism is believed to be a loss of homeostasis between cellular proliferation and apoptosis (programmed cell death) within the prostate gland, leading to a net increase in the number of prostatic cells [1].
The hormonal milieu plays a permissive role in the development of BPH. Testicular androgens, particularly testosterone, are essential for the growth and maintenance of the prostate. Within the prostatic stromal cells, testosterone is converted to its more potent metabolite, dihydrotestosterone (DHT), by the enzyme 5-alpha-reductase type 2. DHT has a higher affinity for the androgen receptor and is a primary mediator of prostatic growth. It directly influences the proliferation of both stromal and epithelial cells, contributing to the development of hyperplastic nodules [12]. Interestingly, while androgens are necessary for the development of BPH, studies have not found a direct correlation between circulating levels of testosterone or DHT and the severity of symptoms in men with established BPH [1]. This suggests that other factors, such as local growth factors and cellular signaling pathways, are also critically involved.
The proliferative process in BPH primarily occurs in the transition zone of the prostate. This anatomical region surrounds the proximal urethra, and its enlargement leads to the static component of bladder outlet obstruction (BOO). The increased bulk of the prostate physically compresses the urethral lumen, increasing resistance to urinary flow. In addition to this static obstruction, there is also a dynamic component to BOO in BPH. This is mediated by the increased tone of the prostatic smooth muscle, which is regulated by the autonomic nervous system, primarily through alpha-1 adrenergic receptors. The combination of static and dynamic obstruction results in the characteristic lower urinary tract symptoms (LUTS) associated with BPH.
Over time, the bladder's response to chronic obstruction can lead to further complications. The detrusor muscle of the bladder initially hypertrophies to generate higher pressures to overcome the obstruction. However, this compensatory mechanism can eventually fail, leading to detrusor instability, decreased compliance, and ultimately, decompensation and the development of a hypotonic or atonic bladder. This can result in incomplete bladder emptying, urinary retention, and an increased risk of urinary tract infections and bladder stones. In severe, untreated cases, the sustained high pressures can be transmitted to the upper urinary tract, leading to hydronephrosis and renal impairment.
References
[12] Lepor, H. (2004). Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. Reviews in urology, 6 Suppl 9(Suppl 9), S3–S10.