Pathophysiology and therapy of benign prostatic hyperplasia;Pathophysiologie und therapie der benignen prostata-hyperplasie

Wiener Klinische Wochenschrift

Volumn 120, Issue 13-14, 2008, Pages 390-401

  Sampson, Natalie ^a   Madersbacher, Stephan ^b   Berger, Peter ^a  

^a ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

^b DANUBE HOSPITAL   (Austria)

Author keywords

Aging; Androgen; Inflammation; Prostate; Radical oxygen species; Stroma; TGF

Indexed keywords

ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; ANDROGEN; DUTASTERIDE; FINASTERIDE; HORMONE ANTAGONIST; SEX HORMONE; VITAMIN D DERIVATIVE;

ANDROGEN METABOLISM; AUTONOMIC NERVOUS SYSTEM; CLINICAL FEATURE; EPITHELIUM CELL; GENE EXPRESSION; HISTOLOGY; HUMAN; MEDICAL RESEARCH; PATHOPHYSIOLOGY; PROSTATE; PROSTATE HYPERTROPHY; REVIEW; STROMA CELL;

EID: 51749114650     PISSN: 00435325     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00508-008-0986-5     Document Type: Review

References (116)

1. JT Isaacs 1994 Etiology of benign prostatic hyperplasia Eur Urol 25 Suppl 1 6 9
2. S Madersbacher G Haidinger C Temml CP Schmidbauer 1998 Prevalence of lower urinary tract symptoms in Austria as assessed by an open survey of 2,096 men Eur Urol 34 2 136 141
3. S Madersbacher 2000 Prevalence of lower urinary tract symptoms and urinary incontinence in the elderly: recent data from Austria Wien Klin Wochenschr 112 9 379 380
4. M Caine 1986 The present role of alpha-adrenergic blockers in the treatment of benign prostatic hypertrophy J Urol 136 1 1 4
5. S Madersbacher M Marszalek J Lackner P Berger G Schatzl 2007 The long-term outcome of medical therapy for BPH Eur Urol 51 6 1522 1533
6. KM Verhamme JP Dieleman GS Bleumink JL Bosch BH Stricker MC Sturkenboom 2003 Treatment strategies, patterns of drug use and treatment discontinuation in men with LUTS suggestive of benign prostatic hyperplasia: the Triumph project Eur Urol 44 5 539 545
7. JE McNeal 1988 Normal histology of the prostate Am J Surg Pathol 12 619 633
8. RM Long C Morrissey JM Fitzpatrick RW Watson 2005 Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies Clin Sci (Lond) 108 1 1 11
9. EJ Tokar BB Ancrile GR Cunha MM Webber 2005 Stem/progenitor and intermediate cell types and the origin of human prostate cancer Differentiation 73 9-10 463 473
10. P Berger M Gruschwitz G Spoettl S Dirnhofer S Madersbacher R Gerth 2007 Human chorionic gonadotropin (hCG) in the male reproductive tract Mol Cell Endocrinol 260-262 190 196
11. PJ Gkonos A Krongrad BA Roos 1995 Neuroendocrine peptides in the prostate Urological Research 23 81 87
12. M Srodon JI Epstein 2002 Central zone histology of the prostate: a mimicker of high-grade prostatic intraepithelial neoplasia Hum Pathol 33 5 518 523
13. L van der Heul-Nieuwenhuijsen PJ Hendriksen TH van der Kwast G Jenster 2006 Gene expression profiling of the human prostate zones BJU Int 98 4 886 897
14. M Che D Grignon 2002 Pathology of prostate cancer Cancer Metastasis Rev 21 3-4 381 395
15. Roehrborn CG, McConnell JD (2002) Etiology, pathophysiology, epidemiology and natural history of benign prostatic hyperplasia. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ (eds) Philadelphia. Campbell's Urology, pp 1297-1336
16. H Bonkhoff K Remberger 1998 Morphogenetic concepts of normal and abnormal growth in the human prostate Virchows Archiv 433 195 202
17. DG Bostwick WH Cooner L Denis GW Jones PT Scardino GP Murphy 1992 The association of benign prostatic hyperplasia and cancer of the prostate Cancer 70 1 Suppl 291 301
18. G Untergasser S Madersbacher P Berger 2005 Benign prostatic hyperplasia: age-related tissue-remodeling Exp Gerontol 40 3 121 128
19. S Lee HG Min SH Choi YJ Kim SW Oh YJ Kim 2006 Central obesity as a risk factor for prostatic hyperplasia Obesity (Silver Spring) 14 1 172 179
20. S Rohrmann E Giovannucci WC Willett EA Platz 2007 Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men Am J Clin Nutr 85 2 523 529
21. AP Berger G Bartsch M Deibl H Alber O Pachinger G Fritsche 2006 Atherosclerosis as a risk factor for benign prostatic hyperplasia BJU Int 98 5 1038 1042
22. RJ Mullan EJ Bergstralh SA Farmer DJ Jacobson SJ Hebbring JM Cunningham 2006 Growth factor, cytokine, and vitamin D receptor polymorphisms and risk of benign prostatic hyperplasia in a community-based cohort of men Urology 67 2 300 305
23. N Sampson G Untergasser E Plas P Berger 2007 The ageing male reproductive tract J Pathol 211 2 206 218
24. E Stoner 1990 The clinical development of a 5 alpha-reductase inhibitor, finasteride J Steroid Biochem Mol Biol 37 3 375 378
25. WD Steers 2001 5alpha-reductase activity in the prostate Urology 58 6 Suppl 1 17 24 discussion
26. CG Roehrborn P Siami J Barkin R Damiao K Major-Walker B Morrill 2008 The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study J Urol 179 2 616 621 discussion 21
27. HA Feldman C Longcope CA Derby CB Johannes AB Araujo AD Coviello 2002 Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study J Clin Endocrinol Metab 87 2 589 598
28. DT Baird A Uno JC Melby 1969 Adrenal secretion of androgens and oestrogens J Endocrinol 45 1 135 136
29. JL Mohler CW Gregory OH Ford 3rd D Kim CM Weaver P Petrusz 2004 The androgen axis in recurrent prostate cancer Clin Cancer Res 10 2 440 448
30. T Nishiyama Y Hashimoto K Takahashi 2004 The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer Clin Cancer Res 10 21 7121 7126
31. M Krieg R Nass S Tunn 1993 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 77 2 375 381
32. P Wikstrom N Ohlson P Stattin A Bergh 2007 Nuclear androgen receptors recur in the epithelial and stromal compartments of malignant and non-malignant human prostate tissue several months after castration therapy Prostate 67 12 1277 1284
33. J Heracek H Richard H Martin S Luboslav S Jana K Jitka 2007 Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer Steroids 72 4 375 380
34. DR Bauman S Steckelbroeck DM Peehl TM Penning 2006 Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer Endocrinology 147 12 5806 5816
35. RO Roberts EJ Bergstralh SA Farmer DJ Jacobson SJ Hebbring JM Cunningham 2006 Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia Prostate 66 4 392 404
36. GS Prins MH Jung RL Vellanoweth B Chatterjee AK Roy 1996 Age-dependent expression of the androgen receptor gene in the prostate and its implication in glandular differentiation and hyperplasia Dev Genet 18 99 106
37. LA Garraway D Lin S Signoretti D Waltregny J Dilks N Bhattacharya 2003 Intermediate basal cells of the prostate: in vitro and in vivo characterization Prostate 55 206 218
38. PP Banerjee S Banerjee TR Brown 2001 Increased androgen receptor expression correlates with development of age-dependent, lobe-specific spontaneous hyperplasia of the brown Norway rat prostate Endocrinology 142 4066 4075
39. H Bonkhoff K Remberger 1996 Differentiation pathways and histogenic aspects of normal and abnormal prostatic growth: a stem cell model Prostate 28 98 106
40. EL Salazar E Mercado L Calzada 2005 Prostatic cancer/benign prostatic hypertrophy. Subcellular distribution of estradiol/androgen receptors Arch Androl 51 2 135 139
41. M Uemura K Tamura S Chung S Honma A Okuyama Y Nakamura 2008 Novel 5alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer Cancer Sci 99 81 86
42. P Bonnet E Reiter M Bruyninx B Sente D Dombrowicz J de Leval 1993 Benign prostatic hyperplasia and normal prostate ageing: differences in types I and II 5 alpha-reductase and steroid hormone receptor messenger ribonucleic acid (mRNA) levels, but not in insulin-like growth factor mRNA levels J Clin Endocrinol Metab 77 1203 1208
43. Y Shibata K Ito K Suzuki K Nakano Y Fukabori R Suzuki 2000 Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition Prostate 42 1 45 55
44. M Hiramatsu I Maehara M Ozaki N Harada S Orikasa H Sasano 1997 Aromatase in hyperplasia and carcinoma of the human prostate Prostate 31 2 118 124
45. A Radlmaier HU Eickenberg MS Fletcher RO Fourcade JM Reis Santos OG van Aubel 1996 Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trial using two doses of the aromatase-inhibitor atamestane. Atamestane Study Group Prostate 29 4 199 208
46. PL Harkonen SI Makela 2004 Role of estrogens in development of prostate cancer J Steroid Biochem Mol Biol 92 4 297 305
47. SM Ho 2004 Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates J Cell Biochem 91 3 491 503
48. GR Cunha YZ Wang SW Hayward GP Risbridger 2001 Estrogenic effects on prostatic differentiation and carcinogenesis Reprod Fertil Dev 13 4 285 296
49. Z Weihua S Makela LC Andersson S Salmi S Saji JI Webster 2001 A role for estrogen receptor beta in the regulation of growth of the ventral prostate Proc Natl Acad Sci USA 98 11 6330 6335
50. Z Weihua R Lathe M Warner JA Gustafsson 2002 An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth Proc Natl Acad Sci USA 99 21 13589 13594
51. SJ McPherson SJ Ellem ER Simpson V Patchev KH Fritzemeier GP Risbridger 2007 Essential role for estrogen receptor beta in stromal-epithelial regulation of prostatic hyperplasia Endocrinology 148 2 566 574
52. SF Shariat R Ashfaq C Roehrborn KM Slawin Y Lotan 2005 Expression of survivin and apoptotic biomarkers in benign prostatic hyperplasia J Urol 174 2046 2050
53. M Royuela MI Arenas FR Bethencourt M Sanchez-Chapado B Fraile R Paniagua 2002 Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein kinases in normal, hyperplastic, and carcinomatous human prostate Hum Pathol 33 3 299 306
54. C Cordon-Cardo A Koff M Drobnjak P Capodieci I Osman SS Millard 1998 Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma J Natl Cancer Inst 90 17 1284 1291
55. EM Bruckheimer N Kyprianou 2002 Bcl-2 antagonises the combined apoptotic effect of transforming growth factor beta and dihydrotestosterone in prostate cancer cells Prostate 53 133 142
56. N Kyprianou H Tu SC Jacobs 1996 Apoptotic versus proliferative activities in human benign prostatic hyperplasia Hum Pathol 27 7 668 675
57. G Untergasser R Gander C Lilg G Lepperdinger E Plas P Berger 2005 Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation Mech Ageing Dev 126 1 59 69
58. JA Tuxhorn GE Ayala MJ Smith VC Smith TD Dang DR Rowley 2002 Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling Clin Cancer Res 8 9 2912 2923
59. WW Barclay RD Woodruff MC Hall SD Cramer 2005 A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer Endocrinology 146 13 18
60. A Orimo PB Gupta DC Sgroi F Arenzana-Seisdedos T Delaunay R Naeem 2005 Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion Cell 121 335 348
61. D Giri M Ittmann 2000 Interleukin-1alpha is a paracrine inducer of FGF7, a key epithelial growth factor in benign prostatic hyperplasia Am J Pathol 157 1 249 255
62. F Ropiquet D Giri DJ Lamb M Ittmann 1999 FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation J Urol 162 2 595 599
63. D Giri M Ittmann 2001 Interleukin-8 is a paracrine inducer of fibroblast growth factor 2, a stromal and epithelial growth factor in benign prostatic hyperplasia Am J Pathol 159 1 139 147
64. MC Pollan HA Benghuzzi M Tucci 2003 Growth factor expression in early stages of benign prostatic hyperplasia upon exposure to sustained delivery of androgens Biomed Sci Instrum 39 329 334
65. SN Salm PE Burger S Coetzee K Goto D Moscatelli EL Wilson 2005 TGF-{beta} maintains dormancy of prostatic stem cells in the proximal region of ducts J Cell Biol 170 1 81 90
66. A Migliaccio G Castoria M Di Domenico A Ciociola M Lombardi A De Falco 2006 Crosstalk between EGFR and extranuclear steroid receptors Ann N Y Acad Sci 1089 194 200
67. G Pandini R Mineo F Frasca CT Roberts M Marcelli R Vigneri 2005 Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells Cancer Res 65 1849 1857
68. H Le JT Arnold KK McFann MR Blackman 2006 DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells Am J Physiol Endocrinol Metab 290 5 E952 E960
69. Wu JD, Haugk K, Woodke L, Nelson PS, Coleman I, Plymate S (2006) Interaction of IGF signaling and the androgen receptor in prostate cancer progression. J Cell Biochem 25: epub
70. HG van der Poel 2005 Androgen receptor and TGF-beta1/Smad signaling are mutually inhibitory in prostate cancer Eur Urol 48 1051 1058
71. JL Carey LM Sasur H Kawakubo V Gupta B Christian PM Bailey 2004 Mutually antagonistic effects of androgen and activin in the regulation of prostate cancer cell growth Mol Endocrinol 18 696 707
72. G Brodin P ten Dijke K Funa CH Heldin M Landstrom 1999 Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration Cancer Res 59 11 2731 2738
73. G Chen M Nomura H Morinaga E Matsubara T Okabe K Goto 2005 Modulation of androgen receptor transactivation by FoxH1. A newly identified androgen receptor corepressor J Biol Chem 280 43 36355 36363
74. N Sampson G Untergasser C Lilg L Tadic E Plas P Berger 2007 GAGEC1, a cancer/testis associated antigen family member, is a target of TGF-beta1 in age-related prostatic disease Mech Ageing Dev 128 1 64 66
75. G Kramer D Mitteregger M Marberger 2007 Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol 51 5 1202 1216
76. DG Bostwick G de la Roza P Dundore FA Corica KA Iczkowski 2003 Intraepithelial and stromal lymphocytes in the normal human prostate Prostate 55 3 187 193
77. WW Hochreiter JL Duncan AJ Schaeffer 2000 Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction J Urol 163 1 127 130
78. L Mazzucchelli P Loetscher A Kappeler M Uguccioni M Baggiolini JA Laissue 1996 Monocyte chemoattractant protein-1 gene expression in prostatic hyperplasia and prostate adenocarcinoma Am J Pathol 149 2 501 509
79. L Begley C Monteleon RB Shah JW Macdonald JA Macoska 2005 CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro Aging Cell 4 6 291 298
80. S Lu Z Dong 2006 Characterization of TGF-beta-regulated interleukin-8 expression in human prostate cancer cells Prostate 66 996 1004
81. P Castro C Xia L Gomez DJ Lamb M Ittmann 2004 Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia Prostate 60 2 153 159
82. W Wang A Bergh JE Damber 2004 Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium Prostate 61 1 60 72
83. F Di Silverio C Bosman M Salvatori L Albanesi L Proietti Pannunzi M Ciccariello 2005 Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) Eur Urol 47 1 72 78 discussion 8-9
84. CL Robinette 1988 Sex-hormone induced inflammation and fibromuscular proliferation in the rat lateral prostate Prostate 12 271 286
85. AJ Asirvatham M Schmidt B Gao J Chaudhary 2006 Androgens regulate the immune/inflammatory response and cell survival pathways in rat ventral prostate epithelial cells Endocrinology 147 1 257 271
86. P Zhu SH Baek EM Bourk KA Ohgi I Garcia-Bassets H Sanjo 2006 Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway Cell 124 3 615 629
87. L Nonn L Peng D Feldman DM Peehl 2006 Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: implications for prostate cancer prevention by vitamin D Cancer Res 66 8 4516 4524
88. BY Bao J Yao YF Lee 2006 1{alpha}, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis Carcinogenesis 27 1883 1893
89. C Crescioli A Morelli L Adorini P Ferruzzi M Luconi GB Vannelli 2005 Human bladder as a novel target for vitamin D receptor ligands J Clin Endocrinol Metab 90 2 962 972
90. M Valko D Leibfritz J Moncol MT Cronin M Mazur J Telser 2007 Free radicals and antioxidants in normal physiological functions and human disease Int J Biochem Cell Biol 39 1 44 84
91. L Bergendi L Benes Z Durackova M Ferencik 1999 Chemistry, physiology and pathology of free radicals Life Sci 65 18-19 1865 1874
92. K Goswami H Nandeesha BC Koner DN Nandakumar 2007 A comparative study of serum protein-bound sialic acid in benign and malignant prostatic growth: possible role of oxidative stress in sialic acid homeostasis Prostate Cancer Prostatic Dis 10 4 356 359
93. RA Merendino F Salvo A Saija G Di Pasquale A Tomaino PL Minciullo 2003 Malondialdehyde in benign prostate hypertrophy: a useful marker? Mediators Inflamm 12 2 127 128
94. R Gradini M Realacci A Ginepri G Naso C Santangelo O Cela 1999 Nitric oxide synthases in normal and benign hyperplastic human prostate: immunohistochemistry and molecular biology J Pathol 189 2 224 229
95. AR Shahed DA Shoskes 2001 Correlation of beta-endorphin and prostaglandin E2 levels in prostatic fluid of patients with chronic prostatitis with diagnosis and treatment response J Urol 166 5 1738 1741
96. JM Potts FF Pasqualotto 2003 Seminal oxidative stress in patients with chronic prostatitis Andrologia 35 5 304 308
97. PF Li R Dietz R von Harsdorf 1999 Superoxide induces apoptosis in cardiomyocytes, but proliferation and expression of transforming growth factor-beta1 in cardiac fibroblasts FEBS Lett 448 2-3 206 210
98. 2-generating NADH oxidase in human lung fibroblasts by transforming growth factor beta 1 J Biol Chem 270 51 30334 30338
99. NS Chandel E Maltepe E Goldwasser CE Mathieu MC Simon PT Schumacker 1998 Mitochondrial reactive oxygen species trigger hypoxia-induced transcription Proc Natl Acad Sci USA 95 20 11715 11720
100. A Gorlach T Kietzmann 2007 Superoxide and derived reactive oxygen species in the regulation of hypoxia-inducible factors Methods Enzymol 435 421 446
101. T Kietzmann A Gorlach 2005 Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression Semin Cell Dev Biol 16 4-5 474 486
102. PH Maxwell 2005 Hypoxia-inducible factor as a physiological regulator Exp Physiol 90 6 791 797
103. C Riva C Chauvin C Pison X Leverve 1998 Cellular physiology and molecular events in hypoxia-induced apoptosis Anticancer Res 18 6B 4729 4736
104. I Cucoranu R Clempus A Dikalova PJ Phelan S Ariyan S Dikalov 2005 NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts Circ Res 97 9 900 907
105. B Cat D Stuhlmann H Steinbrenner L Alili O Holtkotter H Sies 2006 Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species J Cell Sci 119 Pt 13 2727 2738
106. NN Tam S Ghatak SM Ho 2003 Sex hormone-induced alterations in the activities of antioxidant enzymes and lipid peroxidation status in the prostate of Noble rats Prostate 55 1 1 8
107. NN Tam I Leav SM Ho 2007 Sex hormones induce direct epithelial and inflammation-mediated oxidative/nitrosative stress that favors prostatic carcinogenesis in the noble rat Am J Pathol 171 4 1334 1341
108. D Roy Q Cai Q Felty S Narayan 2007 Estrogen-induced generation of reactive oxygen and nitrogen species, gene damage, and estrogen-dependent cancers J Toxicol Environ Health B Crit Rev 10 4 235 257
109. CR Chapple R Crowe SA Gilpin J Gosling G Burnstock 1991 The innervation of the human prostate gland - the changes associated with benign enlargement J Urol 146 6 1637 1644
110. H Lepor E Shapiro 1984 Characterization of alpha1 adrenergic receptors in human benign prostatic hyperplasia J Urol 132 6 1226 1229
111. AL Burnett MP Maguire SL Chamness DD Ricker M Takeda H Lepor 1995 Characterization and localization of nitric oxide synthase in the human prostate Urology 45 3 435 439
112. JK Crone AL Burnett SL Chamness JD Strandberg TS Chang 1998 Neuronal nitric oxide synthase in the canine prostate: aging, sex steroid, and pathology correlations J Androl 19 3 358 364
113. K Omori J Kotera 2007 Overview of PDEs and their regulation Circ Res 100 3 309 327
114. S Uckert CG Stief M Mayer U Jonas P Hedlund 2005 Distribution and functional significance of phosphodiesterase isoenzymes in the human lower urinary tract World J Urol 23 6 368 373
115. KT McVary W Monnig JL Camps Jr JM Young LJ Tseng G van den Ende 2007 Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial J Urol 177 3 1071 1077
116. TM Penning DR Bauman Y Jin TL Rizner 2007 Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor Mol Cell Endocrinol 265-266 77 82