Early investigational agents for the treatment of benign prostatic hyperplasia’

References

• Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol. 2005;7(Suppl 9):S3. doi: 10.1038/ncpuro0553
   PubMedGoogle Scholar
• Lepor H. Pathophysiology of lower urinary tract symptoms in the aging male population. Rev Urol. 2005;7(Suppl 7):S3.
   Google Scholar
• Andersson SO, Rashidkhani B, Karlberg L, et al. Prevalence of lower urinary tract symptoms in men aged 45-79 years: a population-based study of 40 000 Swedish men. BJU Int. 2004;94(3):327–331. doi: 10.1111/j.1464-410X.2004.04930.x
   PubMed Web of Science ®Google Scholar
• Coyne KS, Sexton CC, Thompson CL, et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the epidemiology of LUTS (EpiLUTS) study. BJU Int. 2009;104(3):352–360.
   PubMed Web of Science ®Google Scholar
• Alcaraz A, Carballido-Rodríguez J, Unda-Urzaiz M, et al. Quality of life in patients with lower urinary tract symptoms associated with BPH: change over time in real-life practice according to treatment–the QUALIPROST study. Int Urol Nephrol. 2016;48(5):645–656.
   PubMed Web of Science ®Google Scholar
• Roehrborn CG, Bruskewitz R, Nickel GC, et al. Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. The PLESS study group. Eur Urol. 2000;37(5):528–536. doi: 10.1159/000020189
   PubMed Web of Science ®Google Scholar
• Rodriguez-Nieves JA, Macoska JA. Prostatic fibrosis, lower urinary tract symptoms, and BPH. Nat Rev Urol. 2013;10(9):546–550. doi: 10.1038/nrurol.2013.149
   PubMed Web of Science ®Google Scholar
• Azzouni F, Godoy A, Li Y, et al. The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol. 2012;2012:530121. doi: 10.1155/2012/530121
   PubMedGoogle Scholar
• Gacci M, Sebastianelli A, Spatafora P, et al. Best practice in the management of storage symptoms in male lower urinary tract symptoms: a review of the evidence base. Ther Adv Urol. 2017 Dec 7;10(2):79–92. doi: 10.1177/1756287217742837
   PubMed Web of Science ®Google Scholar
• Brown CT, Yap T, Cromwell DA, et al. Self-management for men with lower urinary tract symptoms: randomised controlled trial [published correction appears in BMJ. 2007 Sep 1;335(7617): 0]. BMJ. 2007;334(7583):25. doi: 10.1136/bmj.39010.551319.AE
   PubMedGoogle Scholar
• Lerner LB, McVary KT, Barry MJ, et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA GUIDELINE PART I-Initial work-up and medical management [published correction appears in J urol. 2021 Nov;206(5): 1339]. J Urol. 2021;206(4):806–817. doi: 10.1097/JU.0000000000002183
   PubMed Web of Science ®Google Scholar
• McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349(25):2387–2398. doi: 10.1056/NEJMoa030656
   PubMed Web of Science ®Google Scholar
• van Kerrebroeck P, Chapple C, Drogendijk T, et al. Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: efficacy and safety results from the randomised controlled NEPTUNE trial. Eur Urol. 2013;64(6):1003–1012. doi: 10.1016/j.eururo.2013.07.034
   PubMed Web of Science ®Google Scholar
• Checcucci E, Veccia A, De Cillis S, et al. New ultra-minimally invasive surgical treatment for benign prostatic hyperplasia: a Systematic Review and analysis of comparative outcomes. Eur Urol Open Sci. 2021 Sep 22;33:28–41. doi:10.1016/j.euros.2021.08.009
   PubMedGoogle Scholar
• Yu ZJ, Yan HL, Xu FH, et al. Efficacy and side effects of drugs commonly used for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Front Pharmacol. 2020 2020 May 8;11:658.
   PubMed Web of Science ®Google Scholar
• Roehrborn CG, Siami P, Barkin J, et al. 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 [published correction appears in J urol. 2008 Sep;180(3): 1191]. J Urol. 2008;179(2):616–621. doi: 10.1016/j.juro.2007.09.084
   PubMed Web of Science ®Google Scholar
• Ückert S, Kedia GT, Tsikas D, et al. Emerging drugs to target lower urinary tract symptomatology (Luts)/benign prostatic hyperplasia (BPH): focus on the prostate. World J Urol. 2020;38(6):1423–1435. doi: 10.1007/s00345-019-02933-1
   PubMed Web of Science ®Google Scholar
• Antoniou V, Gauhar V, Modi S. et al. Role of Phytotherapy in the management of BPH: a summary of the literature. J Clin Med. 2023 Feb 28;12(5):1899. doi: 10.3390/jcm12051899
   PubMed Web of Science ®Google Scholar
• EAU Guidelines. Presented at the EAU Annual Congress Milan. Arnhem, the Netherlands. Mar 2023.
   Google Scholar
• Narayan P, Tewari A. A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 study group. J Urol. 1998;160(5):1701–1706. doi: 10.1016/S0022-5347(01)62386-3
   PubMed Web of Science ®Google Scholar
• Foglar R, Shibata K, Horie K, et al. Use of recombinant alpha 1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophy. Eur J Pharmacol. 1995;288(2):201–207.
   PubMed Web of Science ®Google Scholar
• Osman NI, Chapple CR, Cruz F, et al. Silodosin: a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia. Expert Opin Pharmacother. 2012;13(14):2085–2096. doi: 10.1517/14656566.2012.714368
   PubMed Web of Science ®Google Scholar
• MM VD, JJ DLR, Michel MC. Effects of alpha(1)-adrenoceptor antagonists on male sexual function. Drugs. 2006;66(3):287–301. doi: 10.2165/00003495-200666030-00002
   PubMed Web of Science ®Google Scholar
• Hennenberg M, Acevedo A, Wiemer N, et al. Non-Adrenergic, Tamsulosin-Insensitive Smooth Muscle Contraction is sufficient to replace α1 -Adrenergic tension in the human prostate. Prostate. 2017 May;77(7):697–707.
   PubMed Web of Science ®Google Scholar
• Tamalunas A, Sauckel C, Ciotkowska A, et al. Inhibition of human prostate stromal cell growth and smooth muscle contraction by thalidomide: a novel remedy in LUTS? Prostate. 2021 May;81(7):377–389.
   PubMed Web of Science ®Google Scholar
• Kyprianou N, Chon J, Benning CM. Effects of alpha(1)-adrenoceptor (alpha(1)-AR) antagonists on cell proliferation and apoptosis in the prostate: therapeutic implications in prostatic disease. Prostate Suppl. 2000;9:42–46. doi: 10.1002/1097-0045(2000)45:9+<42:aid-pros9>3.0.co;2-u
   PubMedGoogle Scholar
• Hisasue S, Furuya R, Itoh N, et al. Ejaculatory disorder caused by alpha-1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission. Int J Urol. 2006;13(10):1311–1316. doi: 10.1111/j.1442-2042.2006.01535.x
   PubMed Web of Science ®Google Scholar
• Chang RS, Chen TB, O’Malley SS, et al. In vitro studies on L-771,688 (SNAP 6383), a new potent and selective alpha1A-adrenoceptor antagonist. Eur J Pharmacol. 2000;409(3):301–312.
   PubMed Web of Science ®Google Scholar
• Marks LP, Curtis SP, Narayan P, et al., Effects of a highly selective alpha-1a antagonist on urinary flow rate in men with symptomatic BPH. American Urological Association Meeting 2000 May 3; Atlanta, GA. p. Abstract 2770.
   Google Scholar
• Ford AP, Arredondo NF, DR B Jr, et al. RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine hydrochloride), a selective alpha 1A-adrenoceptor antagonist, displays low affinity for functional alpha 1-adrenoceptors in human prostate: implications for adrenoceptor classification. Mol Pharmacol. 1996;49(2):209–215.
   PubMed Web of Science ®Google Scholar
• Huang JJ, Zhang ZH, He F, et al. Novel naftopidil derivatives containing methyl phenylacetate and their blocking effects on α1D/1A-adrenoreceptor subtypes. Bioorg Med Chem Lett. 2018;28(4):547–551. doi: 10.1016/j.bmcl.2018.01.068
   PubMed Web of Science ®Google Scholar
• Farthing MJ, Alstead EM, Abrams SM, et al. Pharmacokinetics of naftopidil, a novel anti-hypertensive drug, in patients with hepatic dysfunction. Postgrad Med J. 1994;70(823):363–366. doi: 10.1136/pgmj.70.823.363
   PubMed Web of Science ®Google Scholar
• Castiglione F, Benigni F, Briganti A, et al. Naftopidil for the treatment of benign prostate hyperplasia: a systematic review. Curr Med Res Opin. 2014;30(4):719–732. doi: 10.1185/03007995.2013.861813
   PubMed Web of Science ®Google Scholar
• Zhang LT, Park JK. Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia? World J Nephrol. 2015;4(1):138–147. doi: 10.5527/wjn.v4.i1.138
   PubMedGoogle Scholar
• Donatucci CF, Brock GB, Goldfischer ER, et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study. BJU Int. 2011;107(7):1110–1116.
   PubMed Web of Science ®Google Scholar
• Porst H, Kim ED, Casabé AR, et al. Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial. Eur Urol. 2011;60(5):1105–1113. doi: 10.1016/j.eururo.2011.08.005
   PubMed Web of Science ®Google Scholar
• Porst H, Oelke M, Goldfischer ER, et al. Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies [published correction appears in urology. 2014 Mar;83(3): 684]. Urology. 2013;82(3):667–673. doi: 10.1016/j.urology.2013.05.005
   PubMed Web of Science ®Google Scholar
• Morelli A, Sarchielli E, Comeglio P, et al. Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. J Sex Med. 2011;8(10):2746–2760. doi: 10.1111/j.1743-6109.2011.02416.x
   PubMed Web of Science ®Google Scholar
• Vignozzi L, Gacci M, Cellai I, et al. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Prostate. 2013;73(13):1391–1402. doi: 10.1002/pros.22686
   PubMed Web of Science ®Google Scholar
• Nagasubramanian S, John NT, Antonisamy B, et al. Tamsulosin and placebo vs tamsulosin and tadalafil in male lower urinary tract symptoms: a double-blinded, randomised controlled trial. BJU Int. 2020;125(5):718–724.
   PubMed Web of Science ®Google Scholar
• Gacci M, Corona G, Salvi M, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61(5):994–1003. doi: 10.1016/j.eururo.2012.02.033
   PubMed Web of Science ®Google Scholar
• Kedia G, Uckert S, Scheller F, et al. In vitro functional responses of isolated normal human prostatic tissue to compounds interacting with the cyclic guanosine monophosphate pathway. Urology. 2006;67(6):1292–1297. doi: 10.1016/j.urology.2005.12.002
   PubMed Web of Science ®Google Scholar
• Klotz T, Mathers MJ, Bloch W, et al. Nitric oxide based influence of nitrates on micturition in patients with benign prostatic hyperplasia. Int Urol Nephrol. 1999;31(3):335–341. doi: 10.1023/a:1007174102953
   PubMedGoogle Scholar
• Roshani A, Khosropanah I, Salehi M, et al. Effects of isosorbide dinitrate on the urinary flow rate in patients with benign prostatic hyperplasia. Urol J. 2010;7(3):183–187.
   PubMed Web of Science ®Google Scholar
• Tadayyon F, Izadpanahi M, Aali S, et al. The effect of sublingual isosorbide dinitrate on acute urinary retention due to benign prostatic hyperplasia. Saudi J Kidney Dis Transpl. 2012;23(4):782–785.
   PubMedGoogle Scholar
• Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry. 2004;75(7):951–957. doi: 10.1136/jnnp.2003.034702
   PubMed Web of Science ®Google Scholar
• Maria G, Brisinda G, Civello IM, et al. Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study. Urology. 2003;62(2):259–265.
   PubMed Web of Science ®Google Scholar
• Crawford ED, Hirst K, Kusek JW, et al. Effects of 100 and 300 units of onabotulinum toxin a on lower urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial. J Urol. 2011;186(3):965–970. doi: 10.1016/j.juro.2011.04.062
   PubMed Web of Science ®Google Scholar
• Sacco E, Bientinesi R, Marangi F, et al. Patient-reported outcomes in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with intraprostatic OnabotulinumtoxinA: 3-month results of a prospective single-armed cohort study. BJU Int. 2012;110(11 Pt C):E837–E844.
   PubMedGoogle Scholar
• Marberger M, Chartier-Kastler E, Egerdie B, et al. A randomized double-blind placebo-controlled phase 2 dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia. Eur Urol. 2013;63(3):496–503. doi: 10.1016/j.eururo.2012.10.005
   PubMed Web of Science ®Google Scholar
• Robert G, Descazeaud A, Karsenty G, et al. Prostatic injection of botulinum toxin is not inferior to optimized medical therapy in the management of lower urinary tract symptoms due to benign prostatic hyperplasia: results of a randomized clinical trial. World J Urol. 2018;36(6):921–929. doi: 10.1007/s00345-018-2193-y
   PubMed Web of Science ®Google Scholar
• Comeglio P, Chavalmane AK, Fibbi B, et al. Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation. J Endocrinol Invest. 2010;33(10):730–738. doi: 10.1007/BF03346679
   PubMed Web of Science ®Google Scholar
• Adorini L, Penna G, Amuchastegui S, et al. Inhibition of prostate growth and inflammation by the vitamin D receptor agonist BXL-628 (elocalcitol). J Steroid Biochem Mol Biol. 2007;103(3–5):689–693. doi: 10.1016/j.jsbmb.2006.12.065
   PubMed Web of Science ®Google Scholar
• Penna G, Fibbi B, Amuchastegui S, et al. The vitamin D receptor agonist elocalcitol inhibits IL-8-dependent benign prostatic hyperplasia stromal cell proliferation and inflammatory response by targeting the RhoA/Rho kinase and NF-kappaB pathways. Prostate. 2009;69(5):480–493.
   PubMed Web of Science ®Google Scholar
• Colli E, Rigatti P, Montorsi F, et al. BXL628, a novel vitamin D3 analog arrests prostate growth in patients with benign prostatic hyperplasia: a randomized clinical trial. Eur Urol. 2006;49(1):82–86. doi: 10.1016/j.eururo.2005.08.014
   PubMed Web of Science ®Google Scholar
• Bakali E, Elliott RA, Taylor AH, et al. Distribution and function of the endocannabinoid system in the rat and human bladder. Int Urogynecol J. 2013;24(5):855–863. doi: 10.1007/s00192-012-1954-1
   PubMed Web of Science ®Google Scholar
• Hedlund P. Cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. Neurourol Urodyn. 2014;33(1):46–53. doi: 10.1002/nau.22442
   PubMed Web of Science ®Google Scholar
• Gratzke C, Weinhold P, Reich O, et al. Transient receptor potential A1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells. Eur Urol. 2010;57(5):902–910. doi: 10.1016/j.eururo.2009.08.019
   PubMed Web of Science ®Google Scholar
• Shore N, Cowan B. The potential for NX-1207 in benign prostatic hyperplasia: an update for clinicians. Ther Adv Chronic Dis. 2011;2(6):377–383. doi: 10.1177/2040622311423128
   PubMedGoogle Scholar
• Denmeade SR, Egerdie B, Steinhoff G, et al. Phase 1 and 2 studies demonstrate the safety and efficacy of intraprostatic injection of PRX302 for the targeted treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2011;59(5):747–754. doi: 10.1016/j.eururo.2010.11.024
   PubMed Web of Science ®Google Scholar
• Elhilali MM, Pommerville P, Yocum RC, et al. Prospective, randomized, double-blind, vehicle controlled, multicenter phase IIb clinical trial of the pore forming protein PRX302 for targeted treatment of symptomatic benign prostatic hyperplasia. J Urol. 2013;189(4):1421–1426. doi: 10.1016/j.juro.2012.11.003
   PubMed Web of Science ®Google Scholar
• Thomas D, Chughtai B, Kini M, et al. Emerging drugs for the treatment of benign prostatic hyperplasia. Expert Opin Emerg Drugs. 2017;22(3):201–212. doi: 10.1080/14728214.2017.1369953
   PubMed Web of Science ®Google Scholar
• Wang S, Bromley E, Xu L, et al. Talaporfin sodium. Expert Opin Pharmacother. 2010;11(1):133–140. doi: 10.1517/14656560903463893
   PubMed Web of Science ®Google Scholar
• Li Z, Habuchi T, Tsuchiya N, et al. Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10. Carcinogenesis. 2004;25(2):237–240.
   PubMed Web of Science ®Google Scholar
• van den Bulk J, NFCC DM, Ten DP. Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression. Clin Sci (Lond). 2021;135(1):35–52. doi: 10.1042/CS20201236
   PubMed Web of Science ®Google Scholar
• Cunha GR, Donjacour AA, Cooke PS, et al. The endocrinology and developmental biology of the prostate. Endocr Rev. 1987;8(3):338–362. doi: 10.1210/edrv-8-3-338
   PubMed Web of Science ®Google Scholar
• Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26(6):833–876. doi: 10.1210/er.2004-0013
   PubMed Web of Science ®Google Scholar
• Liu CC, Huang SP, Li WM, et al. Relationship between serum testosterone and measures of benign prostatic hyperplasia in aging men. Urology. 2007;70(4):677–680. doi: 10.1016/j.urology.2007.05.025
   PubMed Web of Science ®Google Scholar
• Walsh PC, Hutchins GM, Ewing LL. Tissue content of dihydrotestosterone in human prostatic hyperplasis is not supranormal. J Clin Invest. 1983;72(5):1772–1777. doi: 10.1172/JCI111137
   PubMed Web of Science ®Google Scholar
• Kohn TP, Mata DA, Ramasamy R, et al. Effects of testosterone replacement therapy on lower urinary tract symptoms: a systematic review and meta-analysis. Eur Urol. 2016;69(6):1083–1090. doi: 10.1016/j.eururo.2016.01.043
   PubMed Web of Science ®Google Scholar
• Ho CK, Habib FK. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol. 2011;8(1):29–41. doi: 10.1038/nrurol.2010.207
   PubMed Web of Science ®Google Scholar
• Cannarella R, Condorelli RA, Barbagallo F, et al. Endocrinology of the aging prostate: Current concepts. Front Endocrinol. 2021;12:554078. doi: 10.3389/fendo.2021.554078
   PubMed Web of Science ®Google Scholar
• Cheon CK. Practical approach to steroid 5alpha-reductase type 2 deficiency. Eur J Pediatr. 2011;170(1):1–8. doi: 10.1007/s00431-010-1189-4
   PubMed Web of Science ®Google Scholar
• Wilkin RP, Bruchovsky N, Shnitka TK, et al. Stromal 5 alpha-reductase activity is elevated in benign prostatic hyperplasia. Acta Endocrinol (Copenh). 1980;94(2):284–288.
   PubMedGoogle Scholar
• Millar RP, Newton CL. Current and future applications of GnRH, kisspeptin and neurokinin B analogues. Nat Rev Endocrinol. 2013;9(8):451–466. doi: 10.1038/nrendo.2013.120
   PubMed Web of Science ®Google Scholar
• Conn PM, WF C Jr. Gonadotropin-releasing hormone and its analogs. Annu Rev Med. 1994;45(1):391–405. doi: 10.1146/annurev.med.45.1.391
   PubMedGoogle Scholar
• Rozsa B, Nadji M, Schally AV, et al. Receptors for luteinizing hormone-releasing hormone (LHRH) in benign prostatic hyperplasia (BPH) as potential molecular targets for therapy with LHRH antagonist cetrorelix. Prostate. 2011;71(5):445–452. doi: 10.1002/pros.21258
   PubMed Web of Science ®Google Scholar
• Walker LM, Tran S, Robinson JW. Luteinizing hormone–releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects. Clin Genitourin Cancer. 2013;11(4):375–384. doi: 10.1016/j.clgc.2013.05.004
   PubMed Web of Science ®Google Scholar
• Solomon ZJ, Mirabal JR, Mazur DJ, et al. Selective androgen receptor modulators: Current knowledge and clinical applications. Sex Med Rev. 2019;7(1):84–94. doi: 10.1016/j.sxmr.2018.09.006
   PubMed Web of Science ®Google Scholar
• Gao W, Kearbey JD, Nair VA, et al. Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology. 2004;145(12):5420–5428.
   PubMed Web of Science ®Google Scholar
• Nejishima H, Yamamoto N, Suzuki M, et al. Anti-androgenic effects of S-40542, a novel non-steroidal selective androgen receptor modulator (SARM) for the treatment of benign prostatic hyperplasia. Prostate. 2012;72(14):1580–1587. doi: 10.1002/pros.22511
   PubMed Web of Science ®Google Scholar
• Kumar R, Verma V, Sarswat A, et al. Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms–action of two new agents. Invest New Drugs. 2012;30(2):582–593.
   PubMed Web of Science ®Google Scholar
• Gonzalez G, Guendulain C, Maffrand C, et al. Comparison of the effect of the aromatase inhibitor, anastrazole, to the antioestrogen, tamoxifen citrate, on canine prostate and semen. Reprod Domest Anim. 2009;44(Suppl 2):316–319. doi: 10.1111/j.1439-0531.2009.01379.x
   PubMedGoogle Scholar
• La Vignera S, Condorelli RA, Russo GI, et al. Endocrine control of benign prostatic hyperplasia. Andrology. 2016;4(3):404–411. doi: 10.1111/andr.12186
   PubMed Web of Science ®Google Scholar
• Shibata Y, Arai S, Miyazawa Y, et al. Effects of steroidal antiandrogen or 5-alpha-reductase inhibitor on prostate tissue hormone content. Prostate. 2017;77(6):672–680. doi: 10.1002/pros.23315
   PubMed Web of Science ®Google Scholar
• Chen R, Yu Y, Dong X. Progesterone receptor in the prostate: A potential suppressor for benign prostatic hyperplasia and prostate cancer. J Steroid Biochem Mol Biol. 2017;166:91–96. doi: 10.1016/j.jsbmb.2016.04.008
   PubMed Web of Science ®Google Scholar
• Yu Y, Liu L, Xie N, et al. Expression and function of the progesterone receptor in human prostate stroma provide novel insights to cell proliferation control. J Clin Endocrinol Metab. 2013;98(7):2887–2896. doi: 10.1210/jc.2012-4000
   PubMed Web of Science ®Google Scholar
• Noguchi K, Takeda M, Hosaka M, et al. Clinical effects of allylestrenol on patients with benign prostatic hyperplasia (BPH) evaluated with criteria for treatment efficacy in BPH. Hinyokika Kiyo. 2002;48(5):269–273.
   PubMedGoogle Scholar
• Noguchi K, Harada M, Masuda M, et al. Clinical significance of interruption of therapy with allylestrenol in patients with benign prostatic hypertrophy. Int J Urol. 1998;5(5):466–470. doi: 10.1111/j.1442-2042.1998.tb00389.x
   PubMedGoogle Scholar
• Fujimoto K, Hirao Y, Ohashi Y, et al. The effects of chlormadinone acetate on lower urinary tract symptoms and erectile functions of patients with benign prostatic hyperplasia: a prospective multicenter clinical study. Adv Urol. 2013;2013:584678. doi: 10.1155/2013/584678
   PubMedGoogle Scholar
• Popovics P, AV Schally, Block NL, et al. Preclinical therapy of benign prostatic hyperplasia with neuropeptide hormone antagonists. World J Clin Urol. 2014;3(3):184–194.
   Google Scholar
• Siejka A, Schally AV, Block NL, et al. Antagonists of growth hormone-releasing hormone inhibit the proliferation of human benign prostatic hyperplasia cells. Prostate. 2010;70(10):1087–1093. doi: 10.1002/pros.21142
   PubMed Web of Science ®Google Scholar
• Rick FG, Schally AV, Block NL, et al. Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia. Proc Natl Acad Sci U S A. 2011;108(9):3755–3760. doi: 10.1073/pnas.1018086108
   PubMed Web of Science ®Google Scholar
• Popovics P, Schally AV, Salgueiro L, et al. Antagonists of growth hormone-releasing hormone inhibit proliferation induced by inflammation in prostatic epithelial cells. Proc Natl Acad Sci U S A. 2017;114(6):1359–1364. doi: 10.1073/pnas.1620884114
   PubMed Web of Science ®Google Scholar
• Hammarsten J, Högstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia. Eur Urol. 2001;39(2):151–158. doi: 10.1159/000052430
   PubMed Web of Science ®Google Scholar
• Wang JY, Fu YY, Kang DY. The association between metabolic syndrome and characteristics of benign prostatic hyperplasia: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(19):e3243. doi: 10.1097/MD.0000000000003243
   PubMed Web of Science ®Google Scholar
• Xia B, Zhao S, Chen Z, et al. The underlying mechanism of metabolic syndrome on benign prostatic hyperplasia and prostate volume. Prostate. 2020;80(6):481–490. doi: 10.1002/pros.23962
   PubMed Web of Science ®Google Scholar
• Farr OM, Gavrieli A, Mantzoros CS. Leptin applications in 2015: what have we learned about leptin and obesity? Curr Opin Endocrinol Diabetes Obes. 2015;22(5):353–359. doi: 10.1097/MED.0000000000000184
   PubMedGoogle Scholar
• Jung JH, Ahn SV, Song JM, et al. Obesity as a risk factor for prostatic enlargement: a retrospective cohort study in Korea. Int Neurourol J. 2016;20(4):321–328. doi: 10.5213/inj.1632584.292
   PubMed Web of Science ®Google Scholar
• Lagiou P, Signorello LB, Trichopoulos D, et al. Leptin in relation to prostate cancer and benign prostatic hyperplasia. Int J Cancer. 1998;76(1):25–28. doi: 10.1002/(sici)1097-0215(19980330)76:1
   PubMed Web of Science ®Google Scholar
• Habib CN, Al-Abd AM, Tolba MF, et al. Leptin influences estrogen metabolism and accelerates prostate cell proliferation. Life Sci. 2015;121:10–15. doi: 10.1016/j.lfs.2014.11.007
   PubMed Web of Science ®Google Scholar
• Comhaire F, Mahmoud A. Preventing diseases of the prostate in the elderly using hormones and nutriceuticals. Aging Male. 2004;7(2):155–169. doi: 10.1080/13685530412331284722
   PubMedGoogle Scholar
• Nickel JC, Chughtai B, De Nunzio C, et al. Rethinking the role of saw palmetto extract for men with lower urinary tract symptoms in North America. Uro. 2022;2(3):137–150. doi: 10.3390/uro2030017
   Google Scholar
• McVary KT, Roehrborn CG, Avins, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793–1803.
   PubMed Web of Science ®Google Scholar
• Gravas S, Gacci M, Gratzke C, et al. Summary Paper on the 2023 European Association of Urology Guidelines on the Management of Non-neurogenic Male Lower Urinary Tract Symptoms. Eur Assoc Urol. 2023 Aug;84(2): 207–222. doi: 10.1016/j.eururo.2023.04.008. Epub 2023 May 17 PMID: 37202311.
   PubMed Web of Science ®Google Scholar
• Tacklind J, Macdonald R, Rutks I, et al. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2012 Dec 12;12(12): CD001423. doi: 10.1002/14651858.CD001423.pub3
   PubMedGoogle Scholar
• Wilt TJ, Ishani A. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 1998;1:CD001044.
   Google Scholar
• Tamalunas A, Wendt A, Springer F, et al. Permixon®, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells. Life Sci. 2022Nov1; 308.120931. 10.1016/j.lfs.2022.120931
   PubMed Web of Science ®Google Scholar
• Breza J, Dzurny O, Borowka A, et al. Efficacy and acceptability of tadenan® (pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe. Curr Med Res Opin. 2008;14(3):127–139.
   Google Scholar
• Chatelain C, Autet W, Brackman F. Comparison of once and twice daily dosage forms of pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension. Urology. 1999;54(3):473–478. doi: 10.1016/S0090-4295(99)00147-8
   PubMed Web of Science ®Google Scholar
• Klippel KF, Hilt DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of β-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. Br J Urol. 1997;80(3):427–432. doi: 10.1046/j.1464-410X.1997.t01-1-00362.x
   PubMedGoogle Scholar
• Wilt TJ, Ishani A, MacDonald R, et al. Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database Syst Rev. 1999;2011(5): CD001043. doi: 10.1002/14651858.CD001043
   Google Scholar
• Suardi N, Gandaglia G, Nini A, et al. Effects of Difaprost® on voiding dysfunction, histology and inflammation markers in patients with benign prostatic hyperplasia who are candidates for surgical treatment. Minerva Urol Nefrol. 2014;66(2):119–125.
   PubMed Web of Science ®Google Scholar
• Allkanjari O, Vitalone A. What do we know about phytotherapy of benign prostatic hyperplasia? Life Sci. 2015;126:42–56. doi: 10.1016/j.lfs.2015.01.023
   PubMed Web of Science ®Google Scholar
• Li NC, Wu SL, Jin J, et al. [Comparison of different drugs on the treatment of benign prostate hyperplasia]. Zhonghua Wai Ke Za Zhi. 2007;45(14):947–950.
   PubMedGoogle Scholar
• Xu J, Qian WQ, Song JD. [A comparative study on different doses of cernilton for preventing the clinical progression of benign prostatic hyperplasia]. Zhonghua Nan Ke Xue. 2008;14(6):533–537.
   PubMedGoogle Scholar
• Stephens FO, Unit O. Phytoestrogens and prostate cancer: possible preventive role. Med J Aust. 1997;167(3):138–140. doi: 10.5694/j.1326-5377.1997.tb138812.x
   PubMed Web of Science ®Google Scholar
• Trinchieri A. Soy in benign prostate hyperplasia and prostate cancer: a literature review. Longhua Chin Med. 2022;5:9. doi: 10.21037/lcm-21-36
   Google Scholar
• Maserejian NN, Giovannucci EL, McVary KT, et al. Dietary, but not supplemental, intakes of carotenoids and vitamin C are associated with decreased odds of lower urinary tract symptoms in men. J Nutr. 2011 Feb;141(2):267–73.
   PubMed Web of Science ®Google Scholar
• Kahokehr A, Vather R, Nixon A, et al. 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 Feb;111(2):304–311.
   PubMed Web of Science ®Google Scholar
• Ditonno P, Battaglia M, Selvaggio O, et al. Clinical evidence supporting the role of lonidamine for the treatment of BPH. Rev Urol. 2005;7(Suppl 7):S27–S533.
   PubMedGoogle Scholar