What is the pathophysiology of the prostate?

From the Guidelines

The pathophysiology of the prostate is primarily driven by the development of benign prostatic hyperplasia (BPH), which is a multifactorial process involving hormonal changes, particularly the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase, leading to the proliferation of epithelial and stromal cells in the transition zone of the prostate. This process is supported by the most recent and highest quality study available, which highlights the role of DHT in the development of BPH 1.

Key Factors in Prostate Pathophysiology

• Hormonal Changes: The conversion of testosterone to DHT is a critical step in the development of BPH, as DHT has a higher affinity for the androgen receptor and is considered the more potent androgenic steroid hormone.
• Cell Proliferation: The proliferation of epithelial and stromal cells in the transition zone of the prostate leads to an increase in cellular mass, contributing to the development of BPH.
• Age: BPH is nearly ubiquitous in aging males, with increases starting at age 40-45 years, reaching 60% by age 60, and 80% by age 80.
• Lower Urinary Tract Symptoms (LUTS): BPH can lead to LUTS, including storage symptoms such as frequency, urgency, and nocturia, as well as voiding symptoms such as weak stream and straining to urinate.

Disease Processes

• BPH: A histologic diagnosis characterized by the proliferation of glandular epithelial tissue, smooth muscle, and connective tissue within the prostatic transition zone.
• Prostatitis: Inflammation of the prostate, which can be bacterial (acute or chronic) or non-bacterial.
• Prostate Cancer: Develops when genetic mutations cause uncontrolled cell growth, typically in the peripheral zone, involving androgen receptor signaling pathways, tumor suppressor genes, and oncogenes.

Clinical Implications

• Diagnosis: Diagnosis of BPH and other prostate diseases involves a combination of physical examination, laboratory tests, and imaging studies.
• Treatment: Treatment options for BPH and other prostate diseases depend on the severity of symptoms and the underlying cause of the disease, and may include medical therapy, minimally invasive procedures, or surgery.

The pathophysiology of the prostate is complex and multifactorial, involving hormonal changes, cell proliferation, and age-related factors. Understanding these factors is critical for the diagnosis and treatment of prostate diseases, including BPH, prostatitis, and prostate cancer. The most recent and highest quality study available provides valuable insights into the development of BPH and its relationship to hormonal changes, particularly the conversion of testosterone to DHT 1.

From the FDA Drug Label

The symptoms associated with benign prostatic hyperplasia (BPH) are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma The development and enlargement of the prostate gland is dependent on the potent androgen, 5α -dihydrotestosterone (DHT). The pathophysiology of the prostate involves two main components:

• Static component: related to an increase in prostate size caused by a proliferation of smooth muscle cells in the prostatic stroma.
• Dynamic component: a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. The prostate gland's development and enlargement are dependent on the potent androgen 5α-dihydrotestosterone (DHT), which is metabolized from testosterone by Type II 5α-reductase in the prostate gland. 2 3

From the Research

Pathophysiology of Prostate

The pathophysiology of prostate diseases, such as benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE), is complex and not fully understood 4. However, several key factors have been identified:

• The androgen system and androgen receptor play a dominant role in the development of BPH/BPE 4.
• Androgen receptors are expressed in BPH tissue and are activated by dihydrotestosterone, which is synthesized under the control of the 5α-reductase enzyme 4.
• Prostatic inflammation and metabolic parameters have also been recognized as important factors in the development of BPE and lower urinary tract symptoms (LUTS) 4, 5.

Role of 5α-Reductase Inhibitors and Alpha-Blockers

5α-reductase inhibitors (5ARIs) and alpha-blockers are two classes of drugs commonly used to treat BPH:

• 5ARIs, such as finasteride and dutasteride, reduce prostate size and prevent disease progression by inhibiting the synthesis of dihydrotestosterone 4, 5.
• Alpha-blockers, such as doxazosin and tamsulosin, relax the smooth muscle in the prostate and bladder neck, improving urinary flow and reducing symptoms 5, 6.
• Combination therapy with 5ARIs and alpha-blockers has been shown to be more effective than monotherapy in reducing BPH-related symptoms and preventing clinical progression 5, 6.

Impact on Prostate Cancer Risk

The use of 5ARIs and alpha-blockers has also been studied in relation to prostate cancer risk:

• 5ARIs have been shown to decrease the risk of overall prostate cancer, low-grade prostate cancer, and delayed prostate cancer pathologic progression 7, 8.
• Alpha-blockers have not been shown to have a significant impact on prostate cancer risk 7, 8.
• However, both 5ARIs and alpha-blockers have been associated with a higher risk of high-grade prostate cancer, although this does not translate into a higher risk of prostate cancer mortality 7, 8.