Yılmaz ASLAN, Özer GÜZEL, Altuğ TUNCEL, Ali ATAN

Benign prostat hiperplazisi ve erektil disfonksiyon tedavisinde fosfodiesteraz tip 5 enzim inhibitörlerinin rolü var mıdır?

Erektil disfonksiyon (ED), tatmin edici cinsel performans için gerekli ereksiyonu sağ- lama ve sürdürmedeki yetersizliğin süreklilik kazanması hali olarak tanımlanır. Benign prostat hiperplazisi (BPH) ve ED sıklıkla ileri yaşta görülmekte ve ortak fizyopatolojiyi paylaşmaktadırlar. Her iki durum hastanın yaşam kalitesini olumsuz etkileyen önemli sağlık problemleridir. ED tedavisinde fosfodiesteraz tip 5 enzim inhibitörleri (PDE5i), BPHda alfa bloker tedaviler birinci basamak tedavi olarak kullanılmaktadır. Son yıllarda BPHya bağlı alt üriner sistem semptomlarının (AÜSS) tedavisinde PDE5ilerin kullanımı gündeme gelmiş- tir. PDE5iler hem erektil fonksiyonları hem de AÜSS iyileştirerek BPHda monoterapi olmaya adaydır. Bu derlemede BPHya bağlı AÜSS olan hastalarda PDE5ilerin kullanımındaki güncel durum tartışılmaktadır

Is there a role of phosphodiesterase type 5 enzyme ınhibitors in the treatment of benign prostatic hyperplasia and erectile dysfunction?

Erectile dysfunction (ED) is defined as persistent inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. Benign prostatic hyperplasia (BPH) is often seen at advanced age like ED, and they share a common pathophysiologic mechanism. Both are major health problems that negatively affect the patients quality of life. As the first-line treatment, phosphodiesterase type 5 inhibitors (PDE5i) are used for ED, and alpha-blockers for BPH. The using of PDE5i in the treatment of lower urinary tract symptoms (LUTS) due to BPH, has been gaining popularity in recent years. Having therapeutic effects for both erectile function and LUTS, PDE5i are good candidates as a monotherapy in BPH patients. In this review, the current status of PDE5i therapy for patients with LUTS due to BPH is discussed.

PDF

___

1- Roehrborn CG. Pathology of benign prostatic hyperplasia. Int J Impot Res 2008;20 Suppl 3:11-8.
2- Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol 2005;7:3-14.
3- Shapiro E, Lepor H. Pathophysiology of clinical benign prostatic hyperplasia. Urol Clin North Am 1995;22:285-90.
4- Oelke M, Bachmann A, Descazeaud A et al. Guidelines on the Management of Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO). European Association of Urology 2013. http://www.uroweb.org/ gls/pdf/13_Male_LUTS_LR.pdf
5- Gacci M, Eardley I, Giuliano F et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 2011;60:809-25.
6- Lepor H. Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol 2007;9:181-90.
7- NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83-90.
8- Akkus E, Kadioglu A, Esen A et al. Turkish Erectile Dysfunction Prevalence Study Group. Prevalence and correlates of erectile dysfunction in Turkey: a population-based study. Eur Urol 2002;41:298-304. a. Kaynak eklenecek
9- Balcı M, Aslan Y, Aydın AÖ et al. Türk erkeklerinde cinsel fonksiyon bozukluğu taraması: anket çalışması. Ortadoğu Tıp Dergisi 2012:4;108-113.
10- Wespes E, Eardley I, Giuliano F et al. Guidelines on Male Sexual Dysfunction: Erectile dysfunction and premature ejaculation. European Association of Urology 2013. http:// www.uroweb.org/gls/pdf/14_Male%20Sexual%20Dysfunction_LR.pdf
11- Uckert S, Oelke M. Phosphodiesterase (PDE) inhibitors in the treatment of lower urinary tract dysfunction. Br J Clin Pharmacol 2011;72:197-204.
12- Elterman DS, Chughtai B, Lee RK, Te AE, Kaplan SA. Update on Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia. Rev Urol 2012;14:79-86.
13- He W, Manisha S, Victoria AK, Kimberly AD. U.S. Census Bureau, Current Population Reports, P23-209, 65+ in the United States: 2005, U.S. Government Printing Offi ce,Washington, DC 2005.
14- Jacobsen SJ, Girman CJ, Guess HA, Oesterling JE, Lieber MM. New diagnostic and treatment guidelines for benign prostatic hyperplasia. Potential impact in the United States. Arch Intern Med 1995;155:477-81.
15- Rosen R, Altwein J, Boyle P et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol 2003;44:637- 49.
16- Andersson KE, de Groat WC, McVary KT et al. Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. Neurourol Urodyn 2011;30:292- 301.
17- Truss MC, Uckert S, Stief CG, Kuczyk M, Jonas U. Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. I. Identification and characterization. Urol Res 1996;24:123-8.
18- Uckert S, Sandner P, Sigl K et al. Is there a role of the phosphodiesterase type 5 (PDE5) in the control of detrusor smooth muscle? A functional and molecular biology study. J Urol 2009;181:152
19- Kuciel R, Ostrowski W. Phosphodiesterase from human prostate gland. Bull Soc Chim Biol (Paris) 1970;52:1051 1060.
20- Fibbi B, Morelli A, Vignozzi L et al. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010;7:5969
21- Oger S, Behr-Roussel D, Gorny D et al. Signalling pathways involved in sildenafil-induced relaxation of human bladder dome smooth muscle. Br J Pharmacol 2010;160:11351143.
22- 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;8:2746-60.
23- Uckert S, Sormes M, Kedia G et al. Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology 2008;71:526-30.
24- Kedia GT, Uckert S, Kedia M, Kuczyk MA. Effects of phosphodiesterase inhibitors on contraction induced by endothelin-1 of isolated human prostatic tissue. Urology 2009;73:1397-401.
25- Kedia GT, Sonnenberg JE, Kuczyk MA, Uckert S. In vitro functional responses of isolated human urethral tissue to phosphodiesterase (PDE) inhibitors. Eur Urol Suppl 2011;10:291292.
26- Von Heyden B, Jordan U, Schmitz W, Hertle L. Urethral relaxation after electrostimulation in the guinea pig is independent of nitric oxide. J Urol 1997;157:1509-13.
27- Vignozzi L, Morelli A, Sarchielli E et al. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol 2012;212:71-84.
28- Morelli A, Comeglio P, Filippi S et al. Testosterone and farnesoid X receptor agonist INT-747 counteract high fat dietinduced bladder alterations in a rabbit model of metabolic syndrome. J Steroid Biochem Mol Biol 2012;132:80-92.
29- Persson K, Igawa Y, Mattiasson A, Andersson KE. Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro. Br J Pharmacol 1992;107:178-84.
30- Giuliano F, Ückert S, Maggi M et al. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol 2013;63:506-16.
31- McVary KT, Roehrborn CG, Avins AL et al. American Urological Association guideline: management of benign prostatic hyperplasia (BPH). American Urological Association Guideline 2010. http://www.auanet.org/content/ guidelines-and-quality-care/clinical-guidelines.cfm.)
32- McVary KT, Monnig W, Camps JL Jr et al. 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 2007;177:1071-7.
33- Gacci M, Vittori G, Tosi N et al. A randomized, placebocontrolled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med 2012;9:1624-33.
34- Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol 2008;180:1228-34.
35- Broderick GA, Brock GB, Roehrborn CG et al. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction. Urology 2010;75:1452-8.
36- Dmochowski R, Roehrborn C, Klise S et al. Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. J Urol 2010;183:1092-7.
37- 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;61:994-1003.
38- Oelke M, Giuliano F, Mirone V et al. Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol 2012;61:917-25.