Benign Prostatic Hyperplasia Aria F. Olumi, M.D. Division of Urologic Surgery Beth Israel Deaconess Medical Center

Epidemiology 90% of men by age 80 develop histologic evidence of BPH. Prostatic growth initiated at age 30 Prostatic doubling 4.5 years between age 31 to 50 10 years between age 51 to 70 Degree of prostatic enlargement varies

Decreased force of stream Definition BPH is a histologic definition Clinical manifestation is Lower Urinary Tract Symptoms (LUTS) Symptoms: Irritative & Obstructive Frequency Urgency Dysuria Pelvic discomfort Nocturia Incomplete emptying Dribbling Decreased force of stream

Prostatic Anatomy

Prostate size, Urinary Symptoms and BPH Prostate Size vs. Urinary Flow Rate 0.6 0.20 Prostate Size vs. Severity of Symptoms 0.22 0.008 Urinary Flow Rate vs. Severity of Symptoms 0.27 0.005 Barry et al., J Urol 150:351, 1993

BPH Histology Proliferative process of both stromal and epithelial components

Differential Dx of LUTS GU Pathology BPH, UTI, Prostate Cancer, Urethral Cancer, Urethral Stricture, Non-GU Pathology Parkinson’s, CVA, Diabetes Mellitus, CHF, spinal cord injury

Pathophysiology Dynamic components Static components secondary to the tension in the prostate smooth muscle Static components secondary to prostatic enlargement

Pathophysiology Prostatic growth is androgen dependent Androgens KGF EGF IGF TGF- (+) (-) Proliferation Cell Death

Androgens in Prostate Development and Growth OH O OH H Dihydrotestosterone (DHT) 5-Reductase (type 2) Testosterone

Bladder Response to Outlet Obstruction Secondary to BPH Smooth muscle hypertrophy Subsequent increase in collagen mass Poor bladder compliance

Bladder Response to Outlet Obstruction Secondary to BPH Bladder instability/compliance associated with symptoms of frequency and urgency Impaired bladder contractility associated with decreased force of stream, hesitancy, intermittency, increased residual urine volume

Assessment of Urinary Symptoms AUA-Symptom Score No correlation between prostatic growth and urinary symptoms

AUA Symptom Score 1. Incomplete emptying Over the past month, how often have you had a sensation of not emptying your bladder completely after you finish urinating? Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

AUA Symptom Score (Cont.) 2. Frequency Over the past month, how often have you had to urinate again less than two hours after you finish urinating?         Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

AUA Symptom Score (Cont.) 3. Intermittency Over the past month how often have you found you stopped and    started again several times when you urinated?         Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

AUA Symptom Score (Cont.) 4. Urgency Over the past month, how often have you found it difficult to postpone urination? Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

AUA Symptom Score (Cont.) 5. Weak stream Over the past month, how often have you had a weak urinary stream? Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

AUA Symptom Score (Cont.) 6. Straining Over the past month, how often have you had to push or strain to begin urination? Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

AUA Symptom Score (Cont.) 7. Nocturia Over the past month, how many times did you most typically get up to urinate from the time you when to bed at night  until  the time you got up in the morning? Not at all < 1 time in 5 < ½ the time ½ the time More than Almost always 1 2 3 4 5

Quality of Life Due to Urinary Symptoms If you were to spend the rest of life with your urinary condition just the way it is now, how would you feel about that? Mostly satisfied Mostly dissatisfied Delighted Unhappy Terrible Pleased Mixed 1 2 3 4 5 6

Evaluation Detailed history focusing on the urinary tract symptoms, PMH/PSH Physical exam: abdomen, GU, prostate Labs: Urinalysis, BUN, Creatinine, PSA Use the AUA-Symptom Score Index for initial assessment prior to initiating therapy (used to assess symptom severity, response to therapy, and detect symptom progression

Who Needs Therapy for BPH? Do symptoms interrupt daytime activities, sleep, create anxiety, reduce general perception of health or quality of life? Perception of bothersome symptoms may vary significantly for different patients with the same degree of symptom severity

Medical Therapy Watchful Waiting Phytotherapy α-adrenergic receptor antagonists 5- α reductase inhibitor therapy

Watchful Waiting Appropriate for patients with minimal to moderate urinary symptoms due to BPH Many patients (especially in the PMD practice) can be treated with watchful waiting

Phytotherapy Saw Palmetto (Serenoa repens) Grown in Southeastern U.S. and Western Indies Used by Native Americans for impotence, inflammation, infertility and as an expectorant.   

α-Adrenergic Receptors in Bladder and Prostate Alpha Adrenergic Blockers Terazosin (hytrin) Doxazosin (cardura) Tamsulosin (flomax) Prostate

Lower Urinary Tract Symptoms after α-Adrenergic Blocking Therapy

5 α-reductase Inhibitor Therapy for BPH Imperato-McGinley J, et al. Steroid 5-alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science. 1974;186:1213-1215. 2. Walsh PC, et al. Familial incomplete hermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med. 1974;291:944-949.

Finasteride (Proscar) and BPH Therapy O OH O OH H Dihydrotestosterone (DHT) 5-Reductase (type 2) Finasteride Testosterone

Congenital Absence of 5-Reductase (type 2) Other clinical characteristics -Small prostates -No lower urinary tract symptoms

Lower Urinary Tract Symptoms after 5α-Reductase Inhibitor Therapy                                                                    

Other Treatments for BPH Minimally invasive therapy Microwave thermal therapy Transurethral needle ablation Prostatic stents Transurethral Resection of Prostate (TURP) Annual follow-up with PSA and DRE needs to continue Open simple prostatectomy Different than radical prostatectomy for cancer Still have prostatic tissue left