Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a common condition among middle-aged and older men. The stromal and, to a lesser degree, epithelial cells of the prostatic transition zone become hyperplastic, causing the prostate to enlarge. While this zone grows throughout life, the prevalence of BPH increases with age, rising from about 8% in the third decade of life to greater than 90% in the ninth decade.[1] The etiology is multifactorial and not well understood. Family history, age, and hormone concentrations appear to play a role in BPH development. Obesity has also been linked to increased risk of BPH and lower urinary tract symptoms.[2] Testosterone and dihydrotestosterone, while necessary for BPH to occur, are not the sole causes of the condition. The role of estrogen in BPH remains unclear. Other contributing factors include inflammation and diet.[3] Symptoms are related to obstruction of the urethra and include hesitancy, reduced urine flow rate, dribbling, urgency, frequency, and nocturia.

Risk Factors

The following factors are associated with increased risk of BPH:

Aging. BPH occurs more commonly with advancing age.

Family history. Data suggest an autosomal dominant genetic pattern.[4]

Androgen. Higher dihydrotestosterone concentrations are associated with BPH.

Obesity. Excessive adiposity may make detection more difficult via digital rectal examination. Obesity, particularly abdominal obesity, may also increase risk for BPH likely as a result of hyperinsulinemia.[5],[6] Elevated levels of estrogens secondary to conversion from testosterone in adipose tissues may also play a role.

Physical inactivity. The Health Professionals Study and Massachusetts Male Aging Study found lower levels of physical activity to be associated with increased risk for BPH.[7],[8]

Diet. Red meat and elevated fat intake have been shown to increase risk for BPH, while increased vegetable consumption has been shown to decrease risk.[9]

Diabetes. Poor glycemic control has been linked to prostate enlargement.[10]

Diagnosis

Diagnosis begins with a good history, noting relevant signs and symptoms, as well as medications and any medical conditions that may contribute to urinary dysfunction. It can be helpful to administer a scoring test to gauge symptom severity; some examples are American Urologic Association Symptom Score Index and International Prostate Symptom Score. Urinalysis should always be performed to check for blood, crystals, or infection. Digital examination will typically detect prostate enlargement. The surface of the prostate should be smooth and is usually symmetrical; asymmetry or induration suggests malignancy. Some men with large prostates have no obstructive symptoms, while men with small prostates may have obstructive symptoms.

Prostate biopsy, ultrasound, and/or the prostate-specific antigen (PSA) blood test help rule out malignancy and confirm a diagnosis of BPH. Other tests are available to evaluate bladder and urethral function, such as urine flow rate and post-void residual volume. Urination frequency and volume measurements can be helpful, especially if symptoms occur primarily at night. By keeping track of fluid intake and urine output, it is possible to determine if excessive fluid intake may be contributing to urinary frequency and nocturia.

Treatment

The purpose of BPH treatment is to improve the patient’s quality of life. Restriction of fluids for 1-2 hours prior to bedtime may help improve nocturnal frequency. Sitting while urinating can increase bladder emptying for men with BPH.[11]

Observation alone (“watchful waiting”) is appropriate if symptoms are mild or not bothersome.

Medical treatment includes use of alpha-1-adrenergic antagonists, such as prazosin, terazosin, doxazosin, tamsulosin, and alfuzosin, which relax smooth muscle and allow for increased urinary flow rate. These medications are the most common first-line pharmaceutical treatment for BPH. The various drugs in this class appear to have similar efficacy. Choice of drug may be based on side effect profile as well as cost.[12] The most common side effect is orthostatic hypotension, the occurrence of which can be reduced by taking the medication just prior to bedtime.[13]

In cases of moderate or greater prostate enlargement, 5-alpha-reductase inhibitors, such as finasteride and dutasteride, can be administered to block the conversion of testosterone to dihydrotestosterone. 5-alpha reductase inhibitors reduce prostate size and serum PSA levels by 50%, though these changes may take at least three to six months to observe. The most common side effect of this class of medications is sexual dysfunction.[14] A combination of an alpha-adrenergic antagonist and finasteride appears to improve long-term outcomes of BPH.

Anticholinergic medications such as oxybutynin, solifenacin, and tolterodine are a second line option for treatment. They are associated with side effects, such as dry mouth, constipation, and cognitive impairment and so should be used with caution.[15]

Phosphodiesterase-5 inhibitors such as tadalafil and vardenafil may be considered for treatment in patients who have concomitant erectile dysfunction.[16]

Plant extracts from saw palmetto (Serenoa repens), Pygeum africanum, and Secale cereale, along with concentrated beta-sitosterol (a plant sterol), may play treatment roles, but need further investigation.

Surgical options for severe refractory symptoms include transurethral resection of the prostate (TURP), transurethral incision of the prostate, open prostatectomy, laser prostatectomy (or photovaporization), microwave therapy, and transurethral needle ablation, among others. There are varying levels of evidence to support each of the above procedures.

Nutritional Considerations

Research studies have examined the relationship between dietary factors and the risk of BPH. The following factors are associated with reduced risk in epidemiologic studies:

Limiting or avoiding animal products and vegetable oils. Several studies have implicated high total meat and animal product intake in BPH, particularly beef and dairy products.[17],[18],[19],[20] The Health Professionals Follow-Up Study found that higher intakes of total protein, animal protein, and polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vegetable oils, were all associated with BPH.[21],[22]

Including soy products. Asian men have a lower risk for prostate disease compared with their Western counterparts, which may be partly attributable to a higher intake of isoflavones and related compounds in their plant-rich diets.[23],[24] Isoflavones in soy foods may inhibit 5-alpha reductase and aromatase, which, in turn, reduces the age-related increase in estrogen’s effect on prostate stromal cell proliferation.[23]

Reducing energy intake. Some studies have shown an association between higher caloric intake and a greater risk for BPH. The Health Professionals Follow-Up Study reported a 50% increased risk for BPH in men in the highest decile of calorie intake compared with those in the lowest decile, as well as a 70% higher risk for moderate-to-severe lower urinary tract symptoms.[21]

Increasing fruit and vegetable intake. The Health Professionals Follow-Up Study found that consumption of fruits and vegetables overall, particularly those rich in beta-carotene, lycopene, lutein, zeaxanthin, and vitamin C, was inversely related to BPH incidence.[25] Examples of these foods are carrots, tomatoes, spinach, sweet potatoes, broccoli, collard greens, corn, oranges, melon, and kiwi. Limited evidence suggests that allium vegetable consumption (e.g., onions, garlic) are also inversely related to BPH incidence.[26] Good glycemic control with lifestyle and dietary modifications is also important given the association between BPH and diabetes. A large case-control study in Italy demonstrated that the risk of BPH requiring surgical treatment decreased with higher intake of vitamin C and iron and increased with the intake of sodium and zinc.[27]

Vitamin D. Multiple studies have confirmed that vitamin D deficiency is associated with prostate enlargement. Data suggests that vitamin D has an inhibitory effect on cyclooxygenase-2 expression and the production of prostaglandin E2 in BPH stromal cells, contributing to the decrease of prostate size in men with BPH.[28],[29]

Orders

See Basic Diet Orders chapter.

Low-fat diet.

Exercise prescription.

What to Tell the Family

Risk of developing BPH can be influenced in part by lifestyle choices and is not necessarily a symptom of aging. Patients should consider following a reduced-fat diet that is free from animal products and includes regular consumption of soy foods. Effective medications are available with minimal side effects. Severe obstructive symptoms (e.g., urinary retention and bladder stones) should be treated with surgery to avoid permanent bladder failure or kidney damage.

References

  1. Berry SJ, Coffey DS, Walsh PC, et al. The development of human benign prostatic hyperplasia with age. J Urol. 1984;132(3):474-9.  [PMID:6206240]
  2. Lee RK, Chung D, Chughtai B, et al. Central obesity as measured by waist circumference is predictive of severity of lower urinary tract symptoms. BJU Int. 2012;110(4):540-5.  [PMID:22243806]
  3. Lee C, Kozlowski JM, Grayhack JT. Intrinsic and extrinsic factors controlling benign prostatic growth. Prostate. 1997;31(2):131-8.  [PMID:9140127]
  4. Sanda MG, Beaty TH, Stutzman RE, et al. Genetic susceptibility of benign prostatic hyperplasia. J Urol. 1994;152(1):115-9.  [PMID:7515446]
  5. Dahle SE, Chokkalingam AP, Gao YT, et al. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol. 2002;168(2):599-604.  [PMID:12131317]
  6. Hammarsten J, Högstedt B, Holthuis N, et al. Components of the metabolic syndrome-risk factors for the development of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 1998;1(3):157-162.  [PMID:12496910]
  7. Meigs JB, Mohr B, Barry MJ, et al. Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol. 2001;54(9):935-44.  [PMID:11520654]
  8. Platz EA, Kawachi I, Rimm EB, et al. Physical activity and benign prostatic hyperplasia. Arch Intern Med. 1998;158(21):2349-56.  [PMID:9827786]
  9. Kristal AR, Arnold KB, Schenk JM, et al. Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. 2008;167(8):925-34.  [PMID:18263602]
  10. Breyer BN, Sarma AV. Hyperglycemia and insulin resistance and the risk of BPH/LUTS: an update of recent literature. Curr Urol Rep. 2014;15(12):462.  [PMID:25287259]
  11. de Jong Y, Pinckaers JH, Ten Brinck RM, et al. Urinating Standing versus Sitting: Position Is of Influence in Men with Prostate Enlargement. A Systematic Review and Meta-Analysis. PLoS ONE. 2014;9(7):e101320.  [PMID:25051345]
  12. Djavan B, Marberger M. A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol. 1999;36(1):1-13.  [PMID:10364649]
  13. Wilt TJ, Mac Donald R, Rutks I. Tamsulosin for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2003.  [PMID:12535426]
  14. Gacci M, Ficarra V, Sebastianelli A, et al. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review and meta-analysis. J Sex Med. 2014;11(6):1554-66.  [PMID:24708055]
  15. McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793-803.  [PMID:21420124]
  16. Liu L, Zheng S, Han P, et al. Phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis. Urology. 2011;77(1):123-9.  [PMID:21195830]
  17. Koskimäki J, Hakama M, Huhtala H, et al. Association of dietary elements and lower urinary tract symptoms. Scand J Urol Nephrol. 2000;34(1):46-50.  [PMID:10757270]
  18. Lagiou P, Wuu J, Trichopoulou A, et al. Diet and benign prostatic hyperplasia: a study in Greece. Urology. 1999;54(2):284-90.  [PMID:10443726]
  19. Chyou PH, Nomura AM, Stemmermann GN, et al. A prospective study of alcohol, diet, and other lifestyle factors in relation to obstructive uropathy. Prostate. 1993;22(3):253-64.  [PMID:7683816]
  20. Araki H, Watanabe H, Mishina T, et al. High-risk group for benign prostatic hypertrophy. Prostate. 1983;4(3):253-64.  [PMID:6189108]
  21. Suzuki S, Platz EA, Kawachi I, et al. Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia. Am J Clin Nutr. 2002;75(4):689-97.  [PMID:11916755]
  22. Nandeesha H. Benign prostatic hyperplasia: dietary and metabolic risk factors. Int Urol Nephrol. 2008;40(3):649-56.  [PMID:18246440]
  23. Gaynor ML. Isoflavones and the prevention and treatment of prostate disease: is there a role? Cleve Clin J Med. 2003;70(3):203-4, 206, 208-9 passim.  [PMID:12678210]
  24. Denis L, Morton MS, Griffiths K. Diet and its preventive role in prostatic disease. Eur Urol. 1999;35(5-6):377-87.  [PMID:10325492]
  25. Rohrmann S, Giovannucci E, Willett WC, et al. Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am J Clin Nutr. 2007;85(2):523-9.  [PMID:17284753]
  26. Galeone C, Pelucchi C, Talamini R, et al. Onion and garlic intake and the odds of benign prostatic hyperplasia. Urology. 2007;70(4):672-6.  [PMID:17991535]
  27. Tavani A, Longoni E, Bosetti C, et al. Intake of selected micronutrients and the risk of surgically treated benign prostatic hyperplasia: a case-control study from Italy. Eur Urol. 2006;50(3):549-54.  [PMID:16442205]
  28. Espinosa G, Esposito R, Kazzazi A, et al. Vitamin D and benign prostatic hyperplasia -- a review. Can J Urol. 2013;20(4):6820-5.  [PMID:23930605]
  29. Zhang W, Zheng X, Wang Y, et al. Vitamin D Deficiency as a Potential Marker of Benign Prostatic Hyperplasia. Urology. 2016;97:212-218.  [PMID:27327576]
Last updated: January 26, 2023