Etiology and disease process of benign prostatic hyperplasia

The natural history of benign prostatic hyperplasia (BPH) involves two phases. The first, or pathological phase of BPH, involves two stages, termed microscopic and macroscopic BPH, neither of which produces symptomatic clinical dysuria. Nearly all men throughout the world will eventually develop microscopic BPH if they live long enough. In only about one-half of the men with microscopic BPH, however, will microscopic BPH grow to produce a macroscopic enlargement of the gland (i.e., macroscopic BPH), suggesting that additional factors are required for the progression of microscopic to macroscopic BPH. Several theories have been proposed to explain the etiology of the pathological phase of BPH. The major theories include the hypotheses that pathological BPH is due to 1) a shift in prostatic androgen metabolism that occurs with aging, which leads to an abnormal accumulation of dihydrotestosterone, thus producing the enlarged prostate (i.e., DHT hypothesis), 2) a change in the prostatic stromal-epithelial interact that occurs with aging, which leads to an inductive effect on prostatic growth (i.e., embryonic reawakening theory), or 3) an increase in the total prostatic stem cell number and/or an increase in the clonal expanding of the stem cells into amplifying and transit cells that occurs with aging (i.e., stem cell theory). The second, or clinical phase of BPH, involves the progression of pathologic BPH to clinical BPH in which the patient develops symptomatic dysuria. Only about one-half the men with macroscopic BPH progress to clinical BPH. Although the macroscopic enlargement of the prostate is a necessary condition for the development of clinical BPH, this enlargement is usually not sufficient by itself for the progression of pathologic BPH to clinical BPH. The etiology of the progression of pathological BPH to clinical BPH requires additional factors (e.g., prostatitis, vascular infarct, tensile strength of the glandular capsule, etc.). A successful treatment for clinical BPH, therefore, does not necessarily require either the prevention or elimination of all degrees of pathologic BPH. Instead, what is needed is a therapy to prevent or reverse the progression of pathologic BPH to the clinical disease.