What causes Benign Prostatic Hyperplasia (BPH)?

Causes of Benign Prostatic Hyperplasia (BPH)

Benign Prostatic Hyperplasia (BPH) is primarily caused by age-related hormonal changes, particularly involving testosterone and dihydrotestosterone (DHT), along with chronic inflammation and metabolic factors that lead to an imbalance between cellular growth and apoptosis in the prostate transition zone. 1, 2

Hormonal Factors

• BPH develops due to an imbalance between cellular growth and apoptosis favoring growth, causing increased cellular mass in the prostatic transition zone 1
• The conversion of testosterone to dihydrotestosterone (DHT) by the 5α-reductase enzyme plays a critical role in prostate growth and BPH development 1, 3
• DHT activates androgen receptors in prostatic tissue, stimulating cellular proliferation 2
• While testosterone is required for BPH development, testosterone levels actually decrease with age, suggesting other factors are involved 4
• Recent studies have found that elevations in plasma estradiol/testosterone ratio contribute to BPH development 4

Age-Related Factors

• Age is the most significant non-modifiable risk factor for BPH, with prevalence increasing dramatically from 40-45 years 1
• BPH affects approximately 60% of men by age 60 and 80% by age 80 1, 5
• Nearly all men will develop microscopic BPH if they live long enough, but only about half will progress to macroscopic enlargement 6
• The prevalence of moderate-to-severe lower urinary tract symptoms (LUTS) rises to nearly 50% by age 80 1

Inflammatory Processes

• Chronic inflammation in the prostate is increasingly recognized as a key contributor to BPH development 2, 7
• Inflammatory processes trigger the production of growth factors that promote cellular proliferation and prostatic enlargement 7
• The American Urological Association recognizes inflammation as an important factor in BPH etiology 8

Metabolic Factors

• Metabolic syndrome (MetS) and its components (obesity, hypertension, dyslipidemia, and hyperglycemia) are associated with increased risk of BPH 9
• Insulin and insulin-like growth factor-I elevations are linked to BPH development 4, 9
• Modifiable lifestyle factors such as inadequate diet, lack of physical exercise, and smoking/drinking behaviors contribute to BPH development 9

Pathophysiological Mechanisms

• BPH contributes to lower urinary tract symptoms (LUTS) through two primary mechanisms: 1, 5
  1. Direct obstruction from enlarged tissue (static component)
  2. Increased smooth muscle tone and resistance (dynamic component)
• The static component relates to prostate size increase caused partly by smooth muscle cell proliferation in the prostatic stroma 3
• The dynamic component involves increased smooth muscle tone in the prostate and bladder neck, mediated by sympathetic nervous stimulation of alpha-1 adrenoceptors 3
• BPH can lead to benign prostatic enlargement (BPE), which can cause obstruction at the bladder neck, termed benign prostatic obstruction (BPO) 1

Cellular and Molecular Mechanisms

• Changes in prostatic stromal-epithelial interactions that occur with aging lead to an inductive effect on prostatic growth (embryonic reawakening theory) 6
• Increases in prostatic stem cell numbers and/or clonal expansion of stem cells into amplifying and transit cells occurs with aging (stem cell theory) 6
• Stem cell activation and cellular proliferation encompassing multiple pathways contribute to BPH development 7

Clinical Implications

• Understanding BPH pathophysiology is essential for developing effective treatment strategies 2
• While macroscopic enlargement of the prostate is necessary for clinical BPH, additional factors (e.g., prostatitis, vascular infarct) are required for progression to symptomatic disease 6
• Regular monitoring is recommended for men with risk factors for BPH progression 1