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BPO/LUTS – Aktuelles zur medikamentösen Therapie

  • Thomas Burtscher
  • Jasmin BekticEmail author
Originalien
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Zusammenfassung

„Lower urinary tract symptoms“ (LUTS) gehören zu den häufigsten Beschwerden der Patienten in der täglichen urologischen Praxis, wobei eine benigne Prostatavergrößerung die häufigste Ursache für LUTS bei Männern darstellt. Für die Therapie, die nur bei subjektiv störender Symptomatik eingeleitet werden sollte, stehen neben einer operativen Sanierung zunächst konservative und medikamentöse Therapiestrategien zur Verfügung. Diverse Phytotherapeutika führen zwar zur Verbesserung der Symptomatik (IPSS [„international prostate symptome score“]) und des Harnstrahls (Qmax), die Krankheitsprogression wird jedoch nicht beeinflusst. Ähnliches, wenn auch deutlich besser untersucht, gilt für die Gruppe der schnell wirksamen α1-Blocker. Bei Patienten mit einem Prostatavolumen <40 ml gelten sie als Mittel der ersten Wahl. Mit einer Reduktion des Prostatavolumens und damit einhergehend einer Verhinderung der Krankheitsprogression bilden 5α-Reduktase-Hemmer eine wichtige Säule in der medikamentösen Therapie der männlichen LUTS. Ein Wirkungseintritt ist jedoch frühestens nach 3‑monatiger Therapiedauer zu erwarten. Mit Tadalafil, 5 mg/Tag, steht auch ein PDE5-Hemmer („Phosphodiesterase-5“) für die Pharmakotherapie der LUTS zur Verfügung. Neben der Verbesserung einer ED („Erektile Dysfunktion“) vermindert die Behandlung auch die LUTS-Symptomatik (IPSS). Patienten, bei denen die Harnspeichersymptomatik vordergründig ist, profitieren von einer Therapie mit verschiedenen Muskarinrezeptorantagonisten. Dabei sollte im Vorfeld eine ausgeprägte subvesikale Obstruktion mit Restharnbildung ausgeschlossen werden. Bei schlechter Verträglichkeit dieser Substanzgruppe (Mundtrockenheit, Obstipation) kann alternativ der Beta-3-Agonist Mirabegron eingesetzt werden, der bei ähnlicher Wirksamkeit besser verträglich ist, sofern keine ausgeprägte Hypertonie bekannt ist. Die angeführten Substanzgruppen wurden in verschiedenen Kombinationen getestet, wobei neben der erwünschten additiven Wirkung auch eine Verstärkung der Nebenwirkungen berücksichtigt werden muss.

Schlüsselwörter

Prostata 5α-Reduktase-Hemmer Tadalafil Phytotherapeutika Mirabregon 

BPO/LUTS—latest news on drug treatment

Abstract

“Lower urinary tract symptoms” (LUTS) are among the most common complaints of urological patients. Benign prostate enlargement represents the most common cause of LUTS in men and treatment should only be initiated in patients with bothering symptoms. There are various different therapeutic strategies to choose from: phytotherapeutic drugs significantly improve obstructive symptoms (IPSS [“international prostate symptome score”]) and maximum urinary flow (Qmax), yet disease progression is not inhibited. The same applies to the group of the rapid-acting α1-blockers, which are considered as first-line therapy in patients with a prostate volume <40 ml. The 5α-reductase inhibitors are another important therapeutic option for men with symptoms of LUTS and a prostate volume >40 ml, accompanying the effect of prostate volume reduction and concomitant prevention of disease progression—onset of these favorable effects are expected after a therapy period of 3 months. Tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor, has its main indication in the treatment of erectile dysfunction, yet a daily oral dose of 5 mg was also shown to significantly improve LUTS. Patients predominantly suffering from storage symptoms can benefit from oral therapy with a muscarinic receptor antagonist. Here, infravesical obstruction should be ruled out in advance and the absence of increased post-void residual urine volume is necessary. Mirabregone, a beta-3 agonist, can be used as a safe alternative in individuals with persistent side effects like xerostomia or constipation, yet is not recommended for patients with severe hypertension. Combination therapies have been subject to many studies in the past and have been shown to achieve more symptom relief when the higher rate of side effects is well tolerated by the patient.

Keywords

Prostate 5α-reductase inhibitors Tadalafil Phytotherapeutic drugs Mirabregone 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

J. Bektic und T. Burtscher geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Literatur

  1. 1.
  2. 2.
    Flanigan RC, Reda DJ, Wasson JH, Anderson RJ, Abdellatif M, Bruskewitz RC (1998) 5‑year outcome of surgical resection and watchful waiting for men with moderately symptomatic benign prostatic hyperplasia: a Department of Veterans Affairs cooperative study. J Urol 160(1):12–16 (discussion 6–7)PubMedGoogle Scholar
  3. 3.
    Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, Mulligan K et al (2007) Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ 334(7583):25PubMedGoogle Scholar
  4. 4.
    Yap TL, Brown C, Cromwell DA, van der Meulen J, Emberton M (2009) The impact of self-management of lower urinary tract symptoms on frequency-volume chart measures. BJU Int 104(8):1104–1108PubMedGoogle Scholar
  5. 5.
    Levin RM, Das AK (2000) A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa repens. Urol Res 28(3):201–209PubMedGoogle Scholar
  6. 6.
    Buck AC (2004) Is there a scientific basis for the therapeutic effects of serenoa repens in benign prostatic hyperplasia? Mechanisms of action. J Urol 172(5 Pt 1):1792–1799PubMedGoogle Scholar
  7. 7.
    Madersbacher S, Berger I, Ponholzer A, Marszalek M (2008) Plant extracts: sense or nonsense? Curr Opin Urol 18(1):16–20PubMedGoogle Scholar
  8. 8.
    Morgia G, Russo GI, Voce S, Palmieri F, Gentile M, Giannantoni A et al (2014) Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial). Prostate 74(15):1471–1480PubMedGoogle Scholar
  9. 9.
    Tacklind J, Macdonald R, Rutks I, Stanke JU, Wilt TJ (2012) Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD001423.pub3 CrossRefPubMedGoogle Scholar
  10. 10.
    Novara G, Giannarini G, Alcaraz A, Cozar-Olmo JM, Descazeaud A, Montorsi F et al (2016) Efficacy and safety of hexanic lipidosterolic extract of serenoa repens (Permixon) in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. Eur Urol Focus 2(5):553–561PubMedGoogle Scholar
  11. 11.
    Michel MC, Vrydag W (2006) Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 147(Suppl 2):S88–119PubMedPubMedCentralGoogle Scholar
  12. 12.
    Schwinn DA, Roehrborn CG (2008) Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol 15(3):193–199PubMedPubMedCentralGoogle Scholar
  13. 13.
    Schwinn DA et al (2004) Alpha1-adrenoceptor subtype selectivity and lower urinary tract symptoms. Mayo Clin Proc 79:1423–1434PubMedGoogle Scholar
  14. 14.
    Kenny BA et al (1996) Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies. Br J Pharmacol 118:871–878PubMedPubMedCentralGoogle Scholar
  15. 15.
    Akiyama K et al (1999) KMD-3213, a uroselective and long-acting a1a-adrenoceptor antagonist, tested in a novel rat model. J Pharmacol Exp Ther 291:81–91PubMedGoogle Scholar
  16. 16.
    Roehrborn CG, Siami P, Barkin J, Damiao R, Major-Walker K, Nandy I et al (2010) The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4‑year results from the CombAT study. Eur Urol 57(1):123–131PubMedGoogle Scholar
  17. 17.
    Roehrborn CG, Siami P, Barkin J, Damiao R, Major-Walker K, Morrill B et al (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)PubMedGoogle Scholar
  18. 18.
    Roehrborn CG (2006) Three months’ treatment with the alpha1-blocker alfuzosin does not affect total or transition zone volume of the prostate. Prostate Cancer Prostatic Dis 9(2):121–125PubMedGoogle Scholar
  19. 19.
    Boyle P, Robertson C, Manski R, Padley RJ, Roehrborn CG (2001) Meta-analysis of randomized trials of terazosin in the treatment of benign prostatic hyperplasia. Urology 58(5):717–722PubMedGoogle Scholar
  20. 20.
    Djavan B, Chapple C, Milani S, Marberger M (2004) State of the art on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology 64(6):1081–1088PubMedGoogle Scholar
  21. 21.
    Nickel JC, Sander S, Moon TD (2008) A meta-analysis of the vascular-related safety profile and efficacy of alpha-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 62(10):1547–1559PubMedCentralGoogle Scholar
  22. 22.
    Chang DF, Campbell JR (2005) Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 31(4):664–673PubMedGoogle Scholar
  23. 23.
    Andriole G, Bruchovsky N, Chung LW, Matsumoto AM, Rittmaster R, Roehrborn C et al (2004) Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 172(4 Pt 1):1399–1403PubMedGoogle Scholar
  24. 24.
    Naslund MJ, Miner M (2007) A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clin Ther 29(1):17–25PubMedGoogle Scholar
  25. 25.
    Boyle P, Gould AL, Roehrborn CG (1996) Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 48(3):398–405PubMedGoogle Scholar
  26. 26.
    Roehrborn CG, Siami P, Barkin J, Damiao R, Becher E, Minana B et al (2009) The influence of baseline parameters on changes in international prostate symptom score with dutasteride, tamsulosin, and combination therapy among men with symptomatic benign prostatic hyperplasia and an enlarged prostate: 2‑year data from the CombAT study. Eur Urol 55(2):461–471PubMedGoogle Scholar
  27. 27.
    Donohue JF, Sharma H, Abraham R, Natalwala S, Thomas DR, Foster MC (2002) Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of role of finasteride for decreasing operative blood loss. J Urol 168(5):2024–2026PubMedGoogle Scholar
  28. 28.
    Nickel JC, Gilling P, Tammela TL, Morrill B, Wilson TH, Rittmaster RS (2011) Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int 108(3):388–394PubMedGoogle Scholar
  29. 29.
    Giuliano F, Uckert S, Maggi M, Birder L, Kissel J, Viktrup L (2013) The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol 63(3):506–516PubMedGoogle Scholar
  30. 30.
    Morelli A, Sarchielli E, Comeglio P, Filippi S, Mancina R, Gacci M et al (2011) 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 8(10):2746–2760PubMedGoogle Scholar
  31. 31.
    Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA et al (2012) A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 61(5):994–1003PubMedGoogle Scholar
  32. 32.
    Chess-Williams R, Chapple CR, Yamanishi T, Yasuda K, Sellers DJ (2001) The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro. J Auton Pharmacol 21(5–6):243–248PubMedGoogle Scholar
  33. 33.
    Abrams P, Kelleher C, Staskin D, Kay R, Martan A, Mincik I et al (2017) Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY). World J Urol 35(5):827–838PubMedGoogle Scholar
  34. 34.
    Kuo HC, Lee KS, Na Y, Sood R, Nakaji S, Kubota Y et al (2015) Results of a randomized, double-blind, parallel-group, placebo- and active-controlled, multicenter study of mirabegron, a beta3-adrenoceptor agonist, in patients with overactive bladder in Asia. Neurourol Urodyn 34(7):685–692PubMedGoogle Scholar
  35. 35.
    Wagg A, Nitti VW, Kelleher C, Castro-Diaz D, Siddiqui E, Berner T (2016) Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics. Curr Med Res Opin 32(4):621–638PubMedGoogle Scholar
  36. 36.
    McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr., Dixon CM, Kusek JW et al (2003) The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349(25):2387–2398PubMedGoogle Scholar
  37. 37.
    Barkin J, Guimaraes M, Jacobi G, Pushkar D, Taylor S, van Vierssen Trip OB (2003) Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol 44(4):461–466PubMedGoogle Scholar
  38. 38.
    Kaplan SA, Roehrborn CG, Gong J, Sun F, Guan Z (2012) Add-on fesoterodine for residual storage symptoms suggestive of overactive bladder in men receiving alpha-blocker treatment for lower urinary tract symptoms. BJU Int 109(12):1831–1840PubMedGoogle Scholar
  39. 39.
    Yang Y, Zhao XF, Li HZ, Wang W, Zhang Y, Xiao H et al (2007) Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study. Chung Hua I Hsueh Tsa Chih 120(5):370–374Google Scholar
  40. 40.
    Athanasopoulos A, Gyftopoulos K, Giannitsas K, Fisfis J, Perimenis P, Barbalias G (2003) Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study. J Urol 169(6):2253–2256PubMedGoogle Scholar
  41. 41.
    Ichihara K, Masumori N, Fukuta F, Tsukamoto T, Iwasawa A, Tanaka Y (2015) A randomized controlled study of the efficacy of tamsulosin monotherapy and its combination with mirabegron for overactive bladder induced by benign prostatic obstruction. J Urol 193(3):921–926PubMedGoogle Scholar
  42. 42.
    Choi H, Kim HJ, Bae JH, Kim JH, du Moon G, Cheon J et al (2015) A meta-analysis of long- versus short-acting phosphodiesterase 5 inhibitors: comparing combination use with alpha-blockers and alpha-blocker monotherapy for lower urinary tract symptoms and erectile dysfunction. Int Neurourol J 19(4):237–245PubMedPubMedCentralGoogle Scholar
  43. 43.
    Casabe A, Roehrborn CG, Da Pozzo LF, Zepeda S, Henderson RJ, Sorsaburu S et al (2014) Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. J Urol 191(3):727–733PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Universitätsklinik für UrologieInnsbruckÖsterreich

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