Benign Neoplasia Benign Prostatic Hyperplasia

Benign prostatic hyperplasia is a common problem for men. More than 50% of men older than 60 years have BPH, and this reaches 80% by 80 years of age (Dull et al., 2002; Thorpe and Neal, 2003). The exact pathogenesis of BPH is uncertain, but it is characterized by epithelial and stromal cell proliferation in the periurethral prostate tissue.

The LUTS syndrome (see earlier) overlaps with BPH because up to 30% of men have lower urinary tract symptoms (Thorpe and Neal, 2003). The symptoms defining LUTS were once thought to be solely indicative of BPH. However, LUTS may arise from other disorders (e.g., detrusor dysfunction), and there is a lack of symptomatic correlation with prostate size. However, outflow obstruction from an enlarged prostate may contribute to the development of detrusor dysfunction and urinary retention, referred to as LUTS-BPH.

Diagnosis focuses on patient history, rectal examination, and impact on quality of life. Symptoms can vary over time, even without treatment; however, the course is typically progressive, and 1% to 2% of men with BPH experience acute urinary retention annually (Webber, 2006).Various measures exist for measuring symptom severity. The most widely used and well validated is the International Prostate Symptom Score. This scoring system can discriminate the severity of symptoms and treatment response. However, it does not correlate with anatomic findings or objective measures of urinary flow (Barry and O'Leary, 1995). Prostate-specific antigen (PSA) values may increase with prostate hyperplasia, but the overlap with prostate cancer makes this of limited use in managing BPH (Barry, 2001).

Medical therapies have overtaken surgical as the most common treatments. Alpha-adrenergic blocking drugs improve urinary symptoms in BPH (Wilt et al., 2008). Alpha-adrenergic antagonists block adrenoreceptors in the prostate and bladder neck (Table 40-13). They may also induce prostate epithelial apoptosis (Thorpe and Neal, 2003). Side effects, particularly blood pressure effects, are important, because these drugs will most often be used in older adults (Schulman, 2003). The a-blocker tamsulosin has recently been implicated in association with serious postoperative ocular complications in patients undergoing cataract surgery (Bell et al., 2009).

Prostate tissue is androgen responsive throughout life. 5a-Reductase inhibitors inhibit the conversion of testosterone to dihydrotestosterone, leading to glandular atrophy and reduced prostate volume (20%-30%) (Thorpe and Neal, 2003). It takes many months for these medicines to become effective. Sexual side effects are the most prominent. These drugs also reduce PSA by up to 50%. Based on the Prostate Cancer Prevention Trial, family physicians should discuss potential benefits and harms of 5a-reductase inhibitors (see Prostate Cancer) when using these medications for BPH and LUTS (Kramer et al., 2009). Prostate enlargement can progress

Table 40-13 Pharmacotherapy for Benign Prostatic Hyperplasia

Drug

Dosage

Adverse Effects

Alpha-Adrenergic Blockers

Alfuzosin (UroXatral)

10 mg daily

Cardiovascular: dizziness, postural hypotension, syncope Sexual: ejaculatory dysfunction Systemic: asthenia, drowsiness, fatigue, headache

Doxazosin (Cardura, generic)

1-8 mg daily

Terazosin (Hytrin, generic)

1-10 mg at bedtime

Tamsulosin (Flomax)" +

0.4 mg daily

5a-Reductase Inhibitors

Dutasteride (Avodart)

0.5 mg daily

Sexual: impotence, decreased libido, ejaculatory dysfunction

Finasteride (Proscar)

5 mg daily

From Schulman CC: Lower urinary tract symptoms/benign prostatic hyperplasia: Minimizing morbidity caused by treatment. Urology 2003;62:24-33; Schwinn DA, Price DT, Narayan P: arAdrenoreceptor subtype selectivity and lower urinary tract symptoms. Mayo Clin Proc 2004;79:1423-1434; and Thorpe A, Neal D: Benign prostatic hyperplasia. Lancet 2003;361:1359-1367. *Alpha-1 adrenoreceptor selective.

fAssociated with postoperative complications from cataract surgery.

enough to obstruct the bladder outlet completely, leading to acute urinary retention. If this occurs, catheterization is warranted. The addition of an a-blocker may aid in voiding once the catheter is removed (Thorpe and Neal, 2003). A randomized, double-blind trial of doxazosin and finasteride over 4 years showed that combining these two medications significantly slowed symptomatic progression and reduced the risk of urinary retention and invasive treatment. Treatment was safe, and the effect of combined treatment on symptom scores was greater than the effect of either agent alone (McCo-nnell et al., 2003). In addition to prescription medicines, a number of alternative therapies are available. Saw palmetto extract (Serenoa repens) is one of the most studied herbal medicines (Buck, 2004). Earlier studies found it is as effective as tamsulosin or finasteride for BPH. Other herbal medicines include p-sitosterols (promising), pygeum (African plum, Prunus africanus), and rye grass pollen (cernilton), with efficacy of the latter two uncertain (Webber, 2006).

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