Relief from the Discomfort of BPH

Prostate conditions can affect men's quality of life and the ability to enjoy social situations. The prostate is located in front of the rectum and just below the bladder surrounding the urethra. There are 3 main conditions that affect the prostate: prostatitis (inflammation of the prostate), prostate cancer, and benign prostate hyperplasia (BPH).

Up to 25% of all office visits by young and middle-aged men for complaints involving the genital and urinary systems may be due to prostatitis.^{1 There are 4 types of prostatitis, and treatment is dependent on the underlying cause for each. Only acute bacterial prostatitis and asymptomatic inflammatory prostatitis require antibiotics.}1Prostate cancer is a disease for which the average man over the age of 50 should be tested every year. In 2003, prostate cancer was responsible for 29,554 deaths in the United States.^{2 Prostate-specific antigen (PSA) is a laboratory value that can be obtained by a simple blood draw to screen for prostate cancer. Most doctors consider PSA values below 4.0 ng/mL to be normal.}3 An abnormal PSA value indicates the need for further assessment, because a clinician cannot distinguish between BPH and prostate cancer on the basis of PSA level alone.

BPH

The prevalence of BPH is age-dependent; 75% of men will develop symptoms by age 70 and 90% by age 80.4 The prostate undergoes 2 growth spurts throughout the life span of most men. The first growth spurt is during puberty, and the second begins at age 40 and continues until around age 70. The benign enlargement of the prostate causes hesitancy and difficulty in initiating urination, interruption of flow, weak urine stream, sensation of incomplete emptying, nocturia, frequency, and urgency.The American Urological Association (AUA) Symptom Index5 provides an objective assessment of subjective symptoms. The patient rates the "bothersomeness" of 7 categories of symptoms on a scale of 1 to 5. The higher the AUA score is, the more severe the condition is (Table 1).

BPH symptoms can be exacerbated by other medications, both prescription and OTC. It is important to educate patients about the impact that OTC and prescription medications?by exacerbating BPH symptoms and severity?can have on BPH symptom control. Commonly used OTC cold medications containing pseudoephedrine or phenylephrine can compromise bladder emptying. Diuretics, in large doses, can cause increased urination, which can compound the symptoms that BPH patients experience. Also, medications with considerable anticholinergic adverse effects?such as antihistamines, tricyclic antidepressants, and antispasmodics?can cause urinary retention when combined with BPH pathophysiology.

Only 2 classes of medications can provide treatment and symptom relief for BPH: a-1-adrenergic antagonists and 5-a-reductase inhibitors (Table 2). Watchful waiting and surgery also are viable options in some BPH cases, depending on the patient and the physician.5

a-1-Adrenergic Antagonists

Five a-1-adrenergic antagonists are available in the United States: prazosin (Minipress; Pfizer), terazosin (Hytrin; Abbott Laboratories), doxazosin (Cardura; Pfizer), alfuzosin (UroXatral; sanofi-aventis), and tamsulosin (Flomax; Boehringer Ingelheim). Only 4 of these agents are long-acting a-1-antagonists: terazosin, doxazosin, alfuzosin, and tamsulosin.

This class of drugs has evolved through several generations. The first generation had many serious adverse effects and is no longer used. The second generation, which includes prazosin, terazosin, doxazosin, and alfuzosin, improves voiding symptoms and produces less tachycardia and cardiac arrhythmia. Prazosin is short-acting, is dosed multiple times per day, and is no longer recommended by the AUA.

a-1-adrenergic antagonist agents relax smooth muscle in the prostate and bladder neck, thereby increasing urinary flow rates and reducing postvoid residual urine volume, but they have no effect on decreasing prostate volume or PSA levels. They require 2 to 4 weeks to reach peak effect on BPH symptoms.

Side effects of these medications include orthostatic hypotension and dizziness. Ensuring that the medication is dosed at bedtime and titrated up over several weeks can minimize these side effects. There are fast and slow titration schedules. Younger patients may be able to handle a faster titration. Elderly patients may be physiologically more vulnerable to the hypotensive effects and already may be taking medications that affect blood pressure, and thus they may require a slower titration schedule. If the medication is discontinued for a period of time, retitration may be required.

Alfuzosin is dosed once per day, does not require titration up, and may cause less significant reductions in blood pressure due to its uroselectivity, compared with the other second-generation agents.6Tamsulosin is the only available third-generation agent. It produces a low incidence of hypotension because of its high affinity for prostate-specific a-adrenergic receptors only. Tamsulosin does not require bedtime dosing or titration schedules, unlike the other agents. This drug is a good choice for patients who cannot tolerate hypotension or are taking multiple medications that have hypotensive adverse effects.5-a-Reductase InhibitorsTwo 5-a-reductase inhibitors are approved in the United States: finasteride (Proscar; Merck) and dutasteride (Avodart; GlaxoSmithKline). These agents work to reduce the size of the prostate, slow disease progression, and decrease the need for surgery. They are especially ideal for patients with prostates that are at least 50 g. Unlike the comparatively quick symptom relief of the a-1-adrenergic antagonists, treatment for 6 to 12 months generally is needed before prostate size is sufficiently reduced to improve symptoms with the 5-a-reductase inhibitors. Once treatment is discontinued, prostate size and symptoms return to baseline. 5-a-reductase inhibitors also decrease PSA levels by ~50%. Therefore, interpreting PSA levels while the patient is using these agents requires adjustment.7Sexual dysfunction is a serious adverse effect of 5-a-reductase inhibitor treatment. This dysfunction can include impotence, decreased libido, ejaculation disturbances, and decreased volume of ejaculate. Ejaculation dysfunction incidence seems to double during combination BPH therapy.7 These adverse sexual effects are reversible and uncommon after the first year of therapy.^{4 Tamsulosin and alfuzosin also can cause patients to have low rates of erectile dysfunction.}65-a-Reductase inhibitors can be absorbed through the skin. Women who are pregnant or may be pregnant should not handle these agents because of the possibility of absorption and the potential risk of a fetal anomaly. According to Avodart prescribing information, if contact is made with leaking capsules, the contact area should be washed immediately with soap and water.8

Combination Therapy

Because the 2 classes of medications for BPH work through different mechanisms of action, it is logical to consider using combination therapy. This therapy seems to be ideal for patients with severe symptoms and enlarged prostates of >40 g. The disadvantages of combination therapy include the increased cost and the increased incidence of adverse effects from the 2 agents. Past studies of <12 months of combination therapy did not find superiority over a-1-adrenergic antagonist monotherapy.^{4 In a study of 5 years in duration, combination therapy demonstrated superiority in relief and prevention of BPH symptoms.}9References

1. http://kidney.niddk.nih.gov/kudiseases/pubs/prostatitis. Accessed July 6, 2007.

2. www.cdc.gov/nchs/fastats/prostate.htm. Accessed July 6, 2007.

3. www.cancer.gov/templates/doc.aspx?viewid=4D0E8A1A-5770-4A6F-BAAC- DED5595D97DF. Accessed July 6, 2007.

4. Eure GR, et al. Benign prostatic hyperplasia disease management guide. Montvale, NJ: Thomson PDR; 2005.

5. Barry MJ, et al. The American Urological Association Symptom Index for benign prostatic hyperplasia. J Urol. 1992;148:1549-1557.

6. Lee M. Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia. Am J Health-Syst Pharm. 2003;60:1426-1439.

7. Finasteride monograph. Available at: http://online.lexi.com/crlsql/servlet/crlonline. Accessed July 6, 2007.

8. Avodart prescribing information. Available at: http://us.gsk.com/products/assets/us_avodart.pdf. Accessed July 9, 2007.

9. McConnell JD, et al. The long term effects of medical therapy on the progression of BPH: results from the MTOPS trial. J Urol. 2002;167:1042.