Epidemiology and pathogenesis of benign prostatic hyperplasia
- Glenn R Cunningham, MD
Glenn R Cunningham, MD
- Distinguished Professor Emeritus, Department of Medicine
- Baylor College of Medicine
- Dov Kadmon, MD
Dov Kadmon, MD
- Professor of Urology
- Baylor College of Medicine
Benign prostatic hyperplasia (BPH) is a common problem among older men, and is responsible for considerable disability. The large number of men with the symptoms of this disorder, the easy access to diagnostic tests, and the availability of drug therapy make it appropriate for the primary care provider to participate in the management of men with this disorder. To do so requires an appreciation for what is known regarding the epidemiology and etiology of BPH, which will be reviewed here. The diagnosis and management of this disorder are discussed elsewhere. (See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia" and "Medical treatment of benign prostatic hyperplasia" and "Transurethral procedures for treating benign prostatic hyperplasia".)
The prostate on average weighs 20 grams in normal 21- to 30-year-old men, and the weight changes little thereafter unless the man develops BPH . However, because of the increased prevalence of BPH in older men, the mean prostate weight at autopsy increases after age 50 years (figure 1).
Prevalence — The prevalence of histologically diagnosed prostatic hyperplasia increases from 8 percent in men aged 31 to 40, to 40 to 50 percent in men aged 51 to 60, to over 80 percent in men older than age 80 (figure 2). The Baltimore Longitudinal Study of Aging compared the age-specific prevalence of pathologically defined BPH at autopsy with the clinical prevalence based upon history and the results of digital rectal examination . There was good agreement between the clinical prevalence and autopsy incidence in men of all ages.
A major difficulty in comparing the prevalence of lower urinary tract symptoms (LUTS) among different groups has been the lack of a common definition. The Olmsted County study found the prevalence of moderate or severe LUTS for men in the fifth, sixth, seventh, and eighth decades of life to be 26, 33, 41, and 46 percent, respectively . In a community-based group of 502 men aged 55 to 74 years without prostate cancer, the prevalence of BPH and LUTS was 19 percent using the criteria of a prostate volume above 30 mL and a high International Prostate Symptom Score (IPSS) . However, the prevalence was only 4 percent if the criteria were a prostate volume above 30 mL, a high International Prostate Symptom Score (IPSS), a maximal urinary flow rate below 10 mL/sec, and a post-void residual urine volume greater than 50 mL. (See "Lower urinary tract symptoms in men".)
●Race – Race has some influence on the risk for BPH severe enough to require surgery. While the age-adjusted relative risk (RR) of BPH necessitating surgery is similar in black and white men, black men less than 65 years old may need treatment more often than white men . In a study of 34,624 men, compared with whites, Asians had a lower risk for nocturia (RR 0.7, 95% CI 0.5-0.9), physician diagnosed BPH (RR 0.7, CI 0.2-0.5), and transurethral prostate surgery (RR 0.2, CI 0.1-0.6), while risks for blacks and whites were similar . In the American Male Health Professional Study, men of Asian ancestry were less likely (relative risk 0.4, 95% CI 0.2-0.8) to undergo surgery for BPH as compared with white men . Black men had similar risk to white men in this study. In a community sample of 2480 men in the United States, moderate to severe LUTS were more common in blacks than in whites (41 versus 34 percent) , and blacks had greater total and transitional zone prostate volume [9,10]. However, there is evidence that differences in risk of LUTS is more related to socioeconomic factors such as income and insurance than to race .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132:474.
- Guess HA, Arrighi HM, Metter EJ, Fozard JL. Cumulative prevalence of prostatism matches the autopsy prevalence of benign prostatic hyperplasia. Prostate 1990; 17:241.
- Chute CG, Panser LA, Girman CJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol 1993; 150:85.
- Bosch JL, Hop WC, Kirkels WJ, Schröder FH. Natural history of benign prostatic hyperplasia: appropriate case definition and estimation of its prevalence in the community. Urology 1995; 46:34.
- Sidney S, Quesenberry CP Jr, Sadler MC, et al. Incidence of surgically treated benign prostatic hypertrophy and of prostate cancer among blacks and whites in a prepaid health care plan. Am J Epidemiol 1991; 134:825.
- Kang D, Andriole GL, Van De Vooren RC, et al. Risk behaviours and benign prostatic hyperplasia. BJU Int 2004; 93:1241.
- Platz EA, Kawachi I, Rimm EB, et al. Race, ethnicity and benign prostatic hyperplasia in the health professionals follow-up study. J Urol 2000; 163:490.
- Sarma AV, Wei JT, Jacobson DJ, et al. Comparison of lower urinary tract symptom severity and associated bother between community-dwelling black and white men: the Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's Health Study. Urology 2003; 61:1086.
- Fowler JE Jr, Bigler SA, Kilambi NK, Land SA. Relationships between prostate-specific antigen and prostate volume in black and white men with benign prostate biopsies. Urology 1999; 53:1175.
- Kaplan SA, Reis RB, Staimen VB, Te AE. Is the ratio of transition zone to total prostate volume higher in African-American men than in their Caucasian or Hispanic counterparts? Br J Urol 1998; 82:804.
- Fowke JH, Munro H, Signorello LB, et al. Association between socioeconomic status (SES) and lower urinary tract symptom (LUTS) severity among black and white men. J Gen Intern Med 2011; 26:1305.
- Tsukamoto T, Kumamoto Y, Masumori N, et al. Prevalence of prostatism in Japanese men in a community-based study with comparison to a similar American study. J Urol 1995; 154:391.
- Gu FL, Xia TL, Kong XT. Preliminary study of the frequency of benign prostatic hyperplasia and prostatic cancer in China. Urology 1994; 44:688.
- Lagiou P, Wuu J, Trichopoulou A, et al. Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999; 54:284.
- 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; 75:689.
- 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; 167:925.
- Negri E, Pelucchi C, Talamini R, et al. Family history of cancer and the risk of prostate cancer and benign prostatic hyperplasia. Int J Cancer 2005; 114:648.
- Kristal AR, Schenk JM, Song Y, et al. Serum steroid and sex hormone-binding globulin concentrations and the risk of incident benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol 2008; 168:1416.
- Cetinkaya M, Cetinkaya H, Ulusoy E, et al. Effect of postnecrotic and alcoholic hepatic cirrhosis on development of benign prostatic hyperplasia. Prostate 1998; 36:80.
- Crispo A, Talamini R, Gallus S, et al. Alcohol and the risk of prostate cancer and benign prostatic hyperplasia. Urology 2004; 64:717.
- St Sauver JL, Jacobson DJ, McGree ME, et al. Longitudinal association between prostatitis and development of benign prostatic hyperplasia. Urology 2008; 71:475.
- St Sauver JL, Jacobson DJ, McGree ME, et al. Protective association between nonsteroidal antiinflammatory drug use and measures of benign prostatic hyperplasia. Am J Epidemiol 2006; 164:760.
- Kahokehr A, Vather R, Nixon A, Hill AG. Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. BJU Int 2013; 111:304.
- 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; 54:935.
- Michel MC, Heemann U, Schumacher H, et al. Association of hypertension with symptoms of benign prostatic hyperplasia. J Urol 2004; 172:1390.
- Rohrmann S, Crespo CJ, Weber JR, et al. Association of cigarette smoking, alcohol consumption and physical activity with lower urinary tract symptoms in older American men: findings from the third National Health And Nutrition Examination Survey. BJU Int 2005; 96:77.
- Parsons JK, Carter HB, Partin AW, et al. Metabolic factors associated with benign prostatic hyperplasia. J Clin Endocrinol Metab 2006; 91:2562.
- Schenk JM, Kristal AR, Neuhouser ML, et al. Serum adiponectin, C-peptide and leptin and risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial. Prostate 2009; 69:1303.
- Araujo AB, Yaggi HK, Yang M, et al. Sleep related problems and urological symptoms: testing the hypothesis of bidirectionality in a longitudinal, population based study. J Urol 2014; 191:100.
- Rohr HP, Bartsch G. Human benign prostatic hyperplasia: a stromal disease? New perspectives by quantitative morphology. Urology 1980; 16:625.
- Shapiro E, Becich MJ, Hartanto V, Lepor H. The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia. J Urol 1992; 147:1293.
- Robert G, Descazeaud A, Nicolaïew N, et al. Inflammation in benign prostatic hyperplasia: a 282 patients' immunohistochemical analysis. Prostate 2009; 69:1774.
- Schenk JM, Kristal AR, Neuhouser ML, et al. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol 2010; 171:571.
- Lee KL, Peehl DM. Molecular and cellular pathogenesis of benign prostatic hyperplasia. J Urol 2004; 172:1784.
- Untergasser G, Madersbacher S, Berger P. Benign prostatic hyperplasia: age-related tissue-remodeling. Exp Gerontol 2005; 40:121.
- Imperato-McGinley J, Gautier T, Zirinsky K, et al. Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. J Clin Endocrinol Metab 1992; 75:1022.
- Walsh PC, Wilson JD. The induction of prostatic hypertrophy in the dog with androstanediol. J Clin Invest 1976; 57:1093.
- Barrack ER, Berry SJ. DNA synthesis in the canine prostate: effects of androgen and estrogen treatment. Prostate 1987; 10:45.
- Walsh PC, Hutchins GM, Ewing LL. Tissue content of dihydrotestosterone in human prostatic hyperplasis is not supranormal. J Clin Invest 1983; 72:1772.
- Chodak GW, Kranc DM, Puy LA, et al. Nuclear localization of androgen receptor in heterogeneous samples of normal, hyperplastic and neoplastic human prostate. J Urol 1992; 147:798.
- Giovannucci E, Stampfer MJ, Chan A, et al. CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in U.S. physicians. Prostate 1999; 39:130.
- Kristal AR, Price DK, Till C, et al. Androgen receptor CAG repeat length is not associated with the risk of incident symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial. Prostate 2010; 70:584.
- Mestayer C, Blanchère M, Jaubert F, et al. Expression of androgen receptor coactivators in normal and cancer prostate tissues and cultured cell lines. Prostate 2003; 56:192.
- Agoulnik IU, Krause WC, Bingman WE 3rd, et al. Repressors of androgen and progesterone receptor action. J Biol Chem 2003; 278:31136.
- Gann PH, Hennekens CH, Longcope C, et al. A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate 1995; 26:40.
- Krieg M, Nass R, Tunn S. Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J Clin Endocrinol Metab 1993; 77:375.
- Takase Y, Lévesque MH, Luu-The V, et al. Expression of enzymes involved in estrogen metabolism in human prostate. J Histochem Cytochem 2006; 54:911.
- Meikle AW, Stephenson RA, McWhorter WP, et al. Effects of age, sex steroids, and family relationships on volumes of prostate zones in men with and without prostate cancer. Prostate 1995; 26:253.
- Suzuki K, Ito K, Ichinose Y, et al. Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol 1995; 29:65.
- Partin AW, Oesterling JE, Epstein JI, et al. Influence of age and endocrine factors on the volume of benign prostatic hyperplasia. J Urol 1991; 145:405.
- Gingell JC, Knönagel H, Kurth KH, Tunn UW. Placebo controlled double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia not requiring operation. The Schering 90.062 Study Group. J Urol 1995; 154:399.
- Barrack ER, Bujnovszky P, Walsh PC. Subcellular distribution of androgen receptors in human normal, benign hyperplastic, and malignant prostatic tissues: characterization of nuclear salt-resistant receptors. Cancer Res 1983; 43:1107.
- Denis L, Pagano F, Nonis A, et al. Double-blind, placebo-controlled trial to assess the efficacy and tolerability of mepartricin in the treatment of BPH. Prostate 1998; 37:246.
- Cunha GR, Donjacour AA, Cooke PS, et al. The endocrinology and developmental biology of the prostate. Endocr Rev 1987; 8:338.
- Begun FP, Story MT, Hopp KA, et al. Regional concentration of basic fibroblast growth factor in normal and benign hyperplastic human prostates. J Urol 1995; 153:839.
- Ropiquet F, Giri D, Lamb DJ, Ittmann M. FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. J Urol 1999; 162:595.
- Giri D, Ropiquet F, Ittmann M. FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells. J Cell Physiol 1999; 180:53.
- Wang Q, Stamp GW, Powell S, et al. Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy. J Clin Pathol 1999; 52:29.
- Monti S, Di Silverio F, Lanzara S, et al. Insulin-like growth factor-I and -II in human benign prostatic hyperplasia: relationship with binding proteins 2 and 3 and androgens. Steroids 1998; 63:362.
- Neuhouser ML, Schenk J, Song YJ, et al. Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial. Prostate 2008; 68:1477.
- Wang W, Bergh A, Damber JE. Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate 2004; 61:60.
- Zlotta AR, Egawa S, Pushkar D, et al. Prevalence of inflammation and benign prostatic hyperplasia on autopsy in Asian and Caucasian men. Eur Urol 2014; 66:619.
- Kim HJ, Park JW, Cho YS, et al. Pathogenic role of HIF-1α in prostate hyperplasia in the presence of chronic inflammation. Biochim Biophys Acta 2013; 1832:183.
- Zenzmaier C, Kern J, Sampson N, et al. Phosphodiesterase type 5 inhibition reverts prostate fibroblast-to-myofibroblast trans-differentiation. Endocrinology 2012; 153:5546.
- Lopez DS, Peskoe SB, Tsilidis KK, et al. Association of variants in genes related to the immune response and obesity with BPH in CLUE II. Prostate Cancer Prostatic Dis 2014; 17:353.
- Claus S, Berges R, Senge T, Schulze H. Cell kinetic in epithelium and stroma of benign prostatic hyperplasia. J Urol 1997; 158:217.
- Royuela M, De Miguel MP, Bethencourt FR, et al. IL-2, its receptors, and bcl-2 and bax genes in normal, hyperplastic and carcinomatous human prostates: immunohistochemical comparative analysis. Growth Factors 2000; 18:135.
- Colombel M, Vacherot F, Diez SG, et al. Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia. Br J Urol 1998; 82:380.
- Cardillo M, Berchem G, Tarkington MA, et al. Resistance to apoptosis and up regulation of Bcl-2 in benign prostatic hyperplasia after androgen deprivation. J Urol 1997; 158:212.
- De Marzo AM, Nelson WG, Meeker AK, Coffey DS. Stem cell features of benign and malignant prostate epithelial cells. J Urol 1998; 160:2381.
- Sanda MG, Doehring CB, Binkowitz B, et al. Clinical and biological characteristics of familial benign prostatic hyperplasia. J Urol 1997; 157:876.
- Roberts RO, Rhodes T, Panser LA, et al. Association between family history of benign prostatic hyperplasia and urinary symptoms: results of a population-based study. Am J Epidemiol 1995; 142:965.
- Meikle AW, Bansal A, Murray DK, et al. Heritability of the symptoms of benign prostatic hyperplasia and the roles of age and zonal prostate volumes in twins. Urology 1999; 53:701.
- Sanda MG, Beaty TH, Stutzman RE, et al. Genetic susceptibility of benign prostatic hyperplasia. J Urol 1994; 152:115.
- Pearson JD, Lei HH, Beaty TH, et al. Familial aggregation of bothersome benign prostatic hyperplasia symptoms. Urology 2003; 61:781.
- Descazeaud A, Rubin MA, Hofer M, et al. BPH gene expression profile associated to prostate gland volume. Diagn Mol Pathol 2008; 17:207.
- Cartwright R, Mangera A, Tikkinen KA, et al. Systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men. Eur Urol 2014; 66:752.