David Mobley, MD Chairman Department of Urology Memorial City Medical Center Houston, Tex Neil Baum, MD Associate Professor Department of Urology Tulane University Medical School New Orleans, La

Benign prostatic hyperplasia is a prevalent condition associated with the aging process in men. Although it is a benign condition, the resulting increase in the size of the prostate gland can significantly affect the patient’s quality of life. The majority of cases are asymptomatic and need not be treated, but men with symptoms should be carefully evaluated and appropriately treated. Recent pharmacologic advances have shifted the focus of management of this condition from surgical to medical therapies. Medical treatment consists of oral alpha-blockade or 5-alpha-reductase inhibition. Phytotherapy has also been used successfully. Patients requiring minimally invasive procedures should usually be referred to a urologist.

---

Men (and women) are now living longer than ever before, as a result of developments in medicine and healthy lifestyles. As the life expectancy of men rises and more men are reaching their mature years, the incidence of benign prostatic hyperplasia (BPH), or enlargement of the prostate gland, and the number of men seeking treatment for it will increase. More than half of all 60-year-old American men have BPH.¹ By age 85, the prevalence escalates to 90%. About 1 in 4 men will seek symptomatic relief from this disease by age 80.¹

With the availability of new pharmacotherapies, the treatment of BPH has begun to deviate from surgery to medical management for patients with mild-to-moderate symptoms. One retrospective study compared patients who had surgical treatment for symptomatic BPH before medical therapy was generally available (in 1988) with those treated in 1998, when medical therapy was considered the first-line choice. Compared with a decade earlier, there were 16% more men at risk of BPH-related events in 1998, but there were also 60% fewer transurethral prostatectomy procedures performed.²

The economic costs associated with BPH are staggering. It is estimated that more than $4 billion is spent in the United States each year on BPH management.³ Moreover, the 5-year cost of using combination therapy with an alpha-blocker and a 5-alpha-reductase inhibitor is nearly $8219 per patient, which does not include the indirect costs, such as lost wages and lost productivity.⁴ Operative management of BPH is the second most common surgical procedure after cataract surgery in the United States and costs $3.9 billion annually.⁵

With advances in the pharmacologic management of BPH and the increasing number of individuals affected, it is likely that more men will be seeking treatment from their primary care physician.

Prevalence
The prevalence of histologically diagnosed BPH increases from 8% in men aged 31 to 40, to 40% to 50% in men aged 51 to 60, to more than 80% in men older than 80 years.⁶ The Baltimore Longitudinal Study of Aging compared the age-specific prevalence of pathologically defined BPH at autopsy with the clinical prevalence based on the history and results of digital rectal examination (DRE)7 and found good agreement between clinical prevalence and autopsy incidence in men of all ages.

BPH is one of the inevitable consequences of aging in men. The condition manifests in 3 different ways. Virtually all men will have microscopic BPH on biopsy as they age, many will have a palpably enlarged prostate gland (“macro-BPH”), and some will have symptomatic BPH. Therefore, although all aging men will have at least microscopic BPH, not all will become symptomatic. However, it is only men with symptomatic BPH that require treatment. Men with asymptomatic BPH, regardless of the size of the prostate, do not need treatment.

Etiology
The principal cause of BPH is the stimulation of the 5-alpha-reductase enzyme, which allows the conversion of testosterone to dihydrotestosterone (DHT).⁸ There is a rare congenital enzymatic anomaly in which 5-alpha-reductase is absent. Those affected individuals have ambiguous genitalia at birth and are thought to be female, but they masculinize at puberty. They do not, however, develop BPH.⁹ The discovery of this enzymatic defect led to a better understanding of the pathophysiology of BPH, which consequently led to the development of new pharmacotherapies, with 5-alpha-reductase inhibition as a way to reduce the size of the prostate, and with continuous therapy to prevent further prostatic growth.¹⁰

There is no relationship between BPH and prostate cancer. Men with BPH are not more likely to develop prostate cancer and, therefore, men with BPH also need to have an annual examination as well as a prostate-specific antigen (PSA) screening test for prostate cancer.

Evaluation of Men with BPH
Since aging is the major risk factor for BPH, screening should begin by age 50, and earlier in men who are symptomatic or are at increased risk for the development of prostate cancer. An algorithm for the evaluation and treatment of patients with BPH is presented in Figure 1.

Evaluation of a patient with symptomatic BPH begins with taking the history of any voiding symptoms, which are generally divided into 2 groups—irritative and obstructive. Irritative symptoms include urinary urgency, frequency, and nocturia. Obstructive symptoms include weak stream, hesitancy, incomplete emptying, and an intermittent stream. For most men with BPH, the irritative symptoms are most troublesome. Solving the problem of nocturia is often the motivating factor that drives men to seek treatment for BPH.

Physical examination
Physical examination includes a limited neurologic evaluation; assessment of the lower abdomen to palpate the bladder, external genitalia, and the prostate; and a DRE. The most important part of the DRE is palpation of the prostate gland to check for nodules or asymmetry of the prostate gland. The physician can also roughly estimate the size of the prostate, assess rectal sphincter tone, and search for any palpable rectal masses.

Either the American Urological Association Symptom Index (Table) or the International Prostate Symptom Score (which are very similar) is now considered the gold standard measurement tool for the assessment of BPH symptoms and response to treatment, both in a clinical practice setting and as an outcome measure in randomized, controlled studies.¹¹

Laboratory evaluation
Initial laboratory tests include urinalysis and, in most cases, a PSA blood test. Other tests depend on the clinical presentation and can include urine cultures and measurements of blood urea nitrogen and creatinine levels.

The PSA blood test, which is most valuable as a screening tool for prostate cancer, can also be particularly helpful in the evaluation of BPH when deciding on medical therapy. Men with larger prostates (PSA >1.4 ng/mL) are more likely to respond to 5-alpha-reductase inhibitors, whereas men with PSA less than 1.⁴ ng/mL are likely to respond better to alpha-blockers.

Imaging studies
Imaging of the upper urinary tract is only occasionally necessary, when a suspicion arises of problems involving the upper urinary tract or the presence of hematuria in association with BPH. Intravenous pyelogram, computed tomography, and magnetic resonance imaging all have their place in the evaluation of upper urinary tract problems but not in the routine evaluation of the patient with symptomatic BPH.

Direct visualization of the lower urinary tract with cystoscopy is only necessary in selected situations, such as a history of hematuria, urethral stricture, bladder cancer, or lower urinary tract surgery.¹¹ Ultrasound evaluation is rarely indicated, except in conjunction with biopsy of the prostate.

Drug Therapy: 5-Alpha-Reductase Inhibitors
There are two 5-alpha-reductase isoenzymes, types 1 and 2; type 2 plays the dominant role in the development of BPH and prostate cancer. The exact role of the type 1 isoenzyme remains in debate, but at least on a theoretical basis, inhibition of both types could potentially yield even better clinical results.

Currently, two 5-alpha-reductase inhibitors are available: finasteride (Proscar)—the first agent in this class—which inhibits the type 2 isoenzyme, and dutasteride (Avodart), which inhibits both type 1 and type 2 isoenzymes of 5-alpha-reductase. A strong stimulus for the development of BPH (and prostate cancer) is the presence of DHT, a substrate of testosterone, in the bloodstream and in the prostate gland. The importance of DHT became apparent with the observation that boys who were castrated before puberty and individuals with a variety of genetic diseases that impair androgen production or action do not develop BPH.⁹

The benefit of 5-alpha-reductase inhibitors is that they reduce prostate volume. Both agents have the potential to reduce prostate volume by 25% to 30% and to maintain the reduction over time. It has been demonstrated that although men who have small prostates (ie, <35-40 cc in volume) do have a reduction in volume when taking a 5-alpha-reductase inhibitor, they do not always experience a lessening of symptoms.¹² The best symptomatic responses are seen in men with a prostate volume of more than 35 to 40 cc, which roughly correlates to a PSA value of more than 1.4 ng/mL.¹²

Physicians need to be aware that 5-alpha-reductase inhibitors decrease PSA levels by 50% (range, 40%-60%) after 6 months of therapy.¹³ This lowering of PSA levels should be maintained as long as the patient continues taking the therapy. Any elevation from nadir or failure of the PSA level to decrease by 50% should prompt a referral to a urologist, to rule out the presence of prostate cancer. The patient and the physician should be aware that the “true” PSA level is about twice that obtained when a man has been taking a 5-­alpha-reductase inhibitor for 6 months or more.

Finasteride
Finasteride blocks 5-alpha-reductase type 2. Many randomized, placebo-controlled trials have evaluated this agent for BPH, and one randomized, controlled trial evaluated it for the prevention of prostate cancer, showing that finasteride can prevent or delay the appearance of prostate cancer but that side effects were of concern.¹⁴

The results of the major phase 3 clinical trial of finast­eride, the Proscar Long-Term Efficacy and Safety Study (PLESS), documented significant reductions in urinary retention and BPH-related surgery compared with placebo in more than 3000 men over a 4-year period.¹⁵ The medication was well tolerated, with minimal side effects, most of which were related to sexual dysfunction. In PLESS, the incidences of erectile dysfunction and ejaculatory dysfunction was slightly higher in the treatment group than in the placebo group during the first year of treatment but were essentially identical in both groups during the last 3 years of the study.

Finasteride, 5 mg, is taken once daily, without regard to food intake. Its half-life is approximately 6 hours. Finasteride is metabolized in the liver, primarily through the cytochrome (CY) P450 enzyme system.

Dutasteride
Dutasteride was the second 5-alpha-reductase inhibitor developed. It lowers DHT levels by approximately 94% within a few weeks of instituting therapy.¹⁶ This depression of DHT is maintained for at least 2 years, and there does not appear to be any tachyphylaxis to this effect. Serum testosterone levels increase by about 19%.16

Dutasteride blocks the 2 types of 5-alpha-reductase isoenzymes. Whether there is more clinical benefit from blocking both isoenzymes remains to be clarified. At this time, the amount of prostate size reduction and the decrease in the incidences of acute urinary retention and prostate surgery with dutasteride are very similar to those with finasteride.¹⁶ Whether dutasteride also reduces the risk for prostate cancer remains to be seen; a clinical trial comparing the 2 agents for this outcome is currently underway in the United States.

The dose of dutasteride is 0.5 mg/day, without regard to food intake. Its half-life is approximately 5 weeks. Dutasteride is metabolized through the CYP3A4 pathway. Its side-effect profile is similar to that of finasteride. The number of men dropping out of phase 3 trials because of side effects was very low with both agents.

Alpha-Blockers
The prostate, trigone, and the bladder neck are rich in alpha adrenoreceptors.¹⁷ Stimulation of these receptors constricts the urethra and prostate, resulting in an obstructed voiding pattern and worsening of voiding symptoms. Blockade of these alpha-receptors fairly consistently results in improved voiding symptoms and voiding patterns, with improved urine flow and reduced hesitancy, intermittency, and nocturia.

The alpha-blockers terazosin HCl (Hytrin), doxazosin mesylate (Cardura), tamsulosin HCl (Flomax), and alfuzosin HCl (Uroxatral) were the first oral therapies approved for BPH. Alpha-blockers (or alpha-adrenoreceptor antagonists) have been used for almost 2 decades for this indication.

Terazosin and doxazosin
Terazosin and doxazosin are less-selective alpha-blockers that have provided successful relief for BPH symptoms for nearly 20 years. Neither is selective to the urinary system, and both have also been used to treat arterial hypertension. Alpha-blockade is not a first-line therapy for hypertension, but these agents are often used in conjunction with other antihypertensive drugs. They are also used alone in men who are normotensive, or in some cases mildly hypertensive, for the treatment of the symptoms of BPH.

The emphasis here is on treating the symptoms of BPH, because, unlike the 5-alpha-reductase inhibitors, alpha-blockers do not affect the underlying pathology, namely, the ever-enlarging prostate.

Terazosin and doxazosin, unlike tamsulosin and alfuzosin, do exert an effect on blood pressure, and hence most of their associated side effects are related to decreases in blood pressure. Postural hypotension, although infrequent—especially with tamsulosin and alfuzosin—can ultimately be a limiting factor in dosing these medications.

Both medications need to be titrated in an effort to avoid these side effects. The starting dose for terazosin is 1 mg/day, with titration up to 10 mg/day, depending on side effects and efficacy. Doxazosin is generally titrated from 2 mg/day up to 8 mg/day. The rate of titration for both medications depends on side effects and patient tolerance. Both agents are generally taken at bedtime.

Tamsulosin and alfuzosin
Tamsulosin and alfuzosin have more selective alpha-blocking properties. Both are alpha1A-blockers, making them more specific to the alpha-adrenergic receptors within the prostate and bladder neck. Approximately 70% of the alpha1-receptors in the prostate are of the alpha1A subtype.¹⁸ The uroselectivity of these 2 medications allows them to be given in low doses.

Tamsulosin can be given in doses of 0.4 mg and 0.8 mg daily; it is available only in a 0.4-mg capsule. Alfuzosin is dosed at 10 mg/day, and no titration is necessary. Both should be taken 30 minutes after the same meal each day.

Safety
Alpha-blockers are well tolerated. Approximately 90% of men will have no side effects.¹⁹ There are less cardiovascular side effects with the uroselective agents, but postural hypotension can occur with any of these medications, and it is therefore important to mention this to the patient. Other side effects of alpha-blockers include dizziness, asthenia, somnolence, stuffy nose, and ejaculatory dysfunction. The latter is most common with tamsulosin.²⁰

Alpha-Blocker plus 5-Alpha-Reductase Inhibitor
Since alpha-blockers and 5-alpha-reductase inhibitors exert their effects on different anatomic and physiologic areas of the prostate, it would seem, at least theoretically, that the optimal medical management of BPH would include the use of both medications.

The Veterans Affairs Cooperative Study (VACS) compared terazosin and finasteride, alone or in combination, with placebo²¹ and found that there did not appear to be an advantage to the combination therapy in terms of symptom reduction after 2 years of treatment. On further analysis, it became apparent that the lack of additional improvement in symptoms could be because many men in this study had a small-volume prostate (<40 cc).

This theory was put to the test in the National Institutes of Health–sponsored Medical Therapy of Prostatic Symptoms (MTOPS) trial.¹² In this longer, 4.5-year study conducted in men with generally larger prostates than participants in the VACS, significant benefit was found with the combination therapy of doxazosin plus finasteride over monotherapy or placebo in the end points of urinary retention and BPH-related surgery.

PSA Level a Tool for Selecting Drug Therapy
Doctors are often in a quandary about which drugs to select when treating BPH. A large, multicenter study demonstrated that prostate glands larger than 40 cc are effectively treated with 5-alpha-reductase inhibitors and those smaller than 40 cc are best managed with alpha-blockers.²²

The larger the size of the prostate gland, the higher the level of PSA.²³ Since it is difficult to determine the size of the prostate gland with the examining finger, the PSA becomes an effective barometer of prostate gland size. Patients with a PSA level of less than 1.4 ng/mL are likely to have a prostate gland smaller than 40 cc in size, whereas those with a PSA greater than 1.4 ng/mL probably have a gland that is larger than 40 cc (Figure 2). Using this method, it is recommended that alpha-blockers be used for men with symptomatic BPH and a PSA value less than 1.4 ng/mL and 5-alpha-reductase inhibitors be used for men with lower urinary tract obstructive symptoms and a PSA level greater than 1.4 ng/mL.

Phytotherapy for BPH
Phytotherapy for the treatment of symptomatic BPH has been used for centuries. It is very common in Europe, and its popularity is increasing in the United States. Most clinical trials have used saw palmetto. A search of Medline for articles published from 1966 to 1997 found 18 randomized, controlled trials, mostly comparing saw palmetto with placebo or another phytotherapeutic agent.²⁴ After exhaustive review of the available literature, the conclusion was that saw palmetto extract does relieve lower urinary tract symptoms in some men. This therapy also has a low cost and a favorable side-effect profile.

However, because of the limited length of the studies, the lack of understanding of the mechanism of action of any of these compounds, and the dearth of well-designed randomized, placebo-controlled trials, physicians should maintain some level of skepticism regarding phytotherapy.

The usual dose for saw palmetto is 325 mg once daily or 160 mg twice daily. Side effects are minimal and include erectile dysfunction and gastrointestinal symptoms.

Indications for Urologic Referral
Patients with mild-to-moderate BPH symptoms can be managed initially by the primary care physician. They should be referred to a urologist if they do not respond to medical management or if they have severe symptoms, an elevated PSA level, a prostate nodule, hematuria, urinary retention, a palpable bladder above the pubic symphysis, azotemia, or recurrent urinary tract infections.

Minimally Invasive Therapy
The indications for surgical treatment of BPH include urinary retention, recurring hematuria caused by BPH, recurrent urinary tract infections, and progressive symptoms unresponsive to medical management.

Transurethral resection of the prostate has been the “gold standard” for the surgical treatment of BPH. Improvements in the procedure over the years have made it very safe, and patients usually require only an overnight stay in the hospital. However, there are infrequent adverse events in a small number of patients, including substantial blood loss, urinary incontinence, and erectile dysfunction. Retrograde ejaculation is a common consequence that occurs in 75% of patients after transurethral resection of the prostate.

A number of minimally invasive therapies have been developed and have met with varying degrees of acceptance by urologists and their patients, including many different types and wavelengths of lasers, transurethral microwave thermotherapy, trans­urethral needle ablation, and water-induced thermotherapy.¹¹ Although none of these procedures can claim the same degree of symptom relief as transurethral resection of the prostate, the results obtained in many men with any of these techniques can be adequate. A significant advantage of minimally invasive procedures is the ability to perform most of them using local anesthesia and on an outpatient basis, or even as an office procedure. This makes them less expensive than surgery; the ability to avoid general anesthesia is also very appealing to patients and physicians.

On the Horizon
A very promising treatment for BPH, and possibly for other benign and malignant solid tumors, is lonidamine, a drug originally developed to treat infertility. It has the unique ability to inhibit intracellular glycolysis. Preliminary data suggest that lonidamine is safe and effective for the treatment of the lower urinary tact symptoms associated with BPH. Observed effects include a speedy reduction in serum PSA concentration, decreased prostate volume, increased urinary flow rate, and most important, improved lower urinary tract obstructive and irritative symptoms.²⁵

Conclusion
Most men over the age of 50 will experience lower urinary tract obstructive symptoms, the most common cause of which is BPH. Measuring the PSA level is an effective surrogate for estimating the size of the prostate. Men with small prostate glands are best treated with alpha-blockers. Men with large prostate glands are best treated with 5-alpha-reductase inhibitors, alone or in combination with an alpha-blocker.

Disclosure
Dr Baum serves on the Speaker’s Bureau of Merck, GlaxoSmithKline, and Sanofi-Aventis.

Self-assessment test
1. All these statements about BPH are true, except:
A. It is inevitable with aging
B. All men with microscopic BPH have symptoms
C. Men with congenital absence of 5-alpha-reductase do not develop BPH
D. Screening should begin by age 50

2. Which of the following diagnostic modalities is NOT usually required in the evaluation of BPH?
A. A history of voiding symptoms
B. DRE
C. Urinalysis
D. Magnetic resonance imaging

3. Which of these initial dosages is NOT appropriate for the treatment of BPH?
A. Dutasteride, 1 mg/day
B. Finasteride, 5 mg/day
C. Alfuzosin, 10 mg/day
D. Doxazosin, 2 mg/day

4. Which of these treatments would NOT be appropriate for a man with symptomatic BPH?
A. Doxazosin plus finasteride in a man with a pros­tate size of 42 cc
B. Doxazosin monotherapy in a man with a PSA level of 1.6 ng/mL
C. Finasteride monotherapy in a man with a pros­tate size of 44 cc
D. Dutasteride monotherapy in a man with a PSA level of 1.7 ng/mL

5. All these signs are indications for the surgical treatment of BPH, except:
A. Azotemia
B. Urinary retention
C. Recurrent urinary tract infection
D. Recurring hematuria caused by BPH

References
1. Chute CG, Panser LA, Girman CJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol. 1993; 150:85-89.

2. Borth CS, Beiko DT, Nickel JC, et al. Impact of medical therapy on transurethral resection of the prostate: a decade of change. Urology. 2001;57:1082-1086.

3. Kortt MA, Bootman JL. The economics of benign prostatic hyperplasia treatment: a literature review. Clin Ther. 1996;18:1227-1241.

4. Naslund MJ, Carlson AM, Williams MJ. A cost comparison of medical management and transurethral needle ablation for treatment of benign prostatic hyperplasia during a 5-year period. J Urol. 2005; 173:2090-2093.

5. Saigal CS, Joyce G. Economic costs of benign prostatic hyperplasia in the private sector. J Urol. 2005;173:1309-1313.

6. Berry SJ, Coffey DS, Walsh PC, et al. The development of human benign prostatic hyperplasia with age. J Urol. 1984;132:474-479.

7. Carter HB, Pearson JD, Metter EJ, et al. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA. 1992;267:2215-2220.

8. McConnell JD. Epidemiology, etiology, pathophysiology, and diagnosis of benign prostatic hyperplasia. In: Walsh PC, Wein AJ, Retik AB, et al, eds. Campbell’s Urology. Vol 2. 7th ed. Philadelphia, Pa: WB Saunders; 1998:1429-1452.

9. Walsh PC, Madden JD, Harrod MJ, et al. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med. 1974;291:944-949.

10. Lam JS, Romas NA, Lowe FC. Long-term treatment with finast­eride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up [abstract]. Paper presented at: American Urological Association Annual Meeting, 2002; Orlando, Fla.

11. American Urological Association Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol. 2003;170:530-547.

12. McConnell JD, Roehrborn CG, Bautista OM, et al, for the Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387-2398.

13. Pannek J, Marks LS, Pearson JD, et al. Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia. J Urol. 1998;159:449-453.

14. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003; 349:215-224.

15. McConnell JD, Bruskewitz R, Walsh P, et al, for the Finasteride Long-Term Efficacy and Safety Study Group. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med. 1998;338:557-563.

16. Roehrborn CG, Boyle P, Nickel JC, et al, for the ARIA3001, ARIA3002, and ARIA3003 Study Investigators. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;60: 434-441.

17. Lepor H. Nonoperative management of benign prostatic hyperplasia. J Urol. 1989;141: 1283-1289.

18. McKeage K, Plosker GL. Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62:633-653.

19. Roehrborn CG. Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001; 58(6 suppl 1):55-64.

20. Roehrborn CG. Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial. Urology. 2001;58:953-959.

21. Lepor H, Williford WO, Barry MJ, et al, for the Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. N Engl J Med. 1996;335:533-539.

22. Marberger MJ. Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group. Urology. 1998;51:677-686.

23. Roehrborn CGT, Boyle P, Gould AL, et al. Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology. 1999;53: 581-589.

24. Wilt TJ, Ishani A, Stark G, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA. 1998;280:1604-1609.

25. Roehrborn CG. The development of lonidamine for benign prostatic hyperplasia and other indications. Rev Urol. 2005;7(suppl):S12-S20.

Practice points BPH prevalence increases with age. Although benign, symptomatic BPH can significantly affect the patient's quality of life. Begin screening for BPH by age 50, and earlier in symptomatic men or those at risk for the development of prostate cancer. Take a history of voiding and perform a DRE to palpate for nodules, masses, and prostate size and symmetry. Medical management is now the preferred modality for most patients, consisting of alpha-blockers and/or 5-alpha-reductase inhibitors.