Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Phosphodiesterase 5 inhibitors in the management of benign prostatic hyperplasia and erectile dysfunction: the best of both worlds Peter Wong, Nathan Lawrentschuk and Damien M. Bolton Introduction In 1986, Caine [1] proposed that infravesical obstruction in men with symptomatic benign prostatic hyperplasia (BPH) comprised both static and dynamic components. The static component of obstruction is related primarily to the mechanical obstruction caused by the enlarging prostatic adenoma, whereas the dynamic component is principally determined by the tone of the prostatic smooth muscle. Two avenues for pharmacotherapy have therefore evolved, namely shrinking the prostate tissue or relaxing the smooth muscle of the prostate. Medical therapy is now first-line treatment for most men with symptomatic benign prostatic hyperplasia [2]. Contem- porary medical therapies are noninvasive, reversible, cause minimal side effects, and significantly improve symptoms [3,4]. Alpha-blockers (alpha 1 -adrenoceptor antagonists) are first line in most instances, with 5- alpha-reductase inhibitors, alone or in combination with alpha-blockers, also clinically efficacious [5]. It is important to note the relationship between lower urinary tract symptoms (LUTS) and sexual dysfunction, with sexual dysfunction being highly prevalent in men with LUTS [6]. By sexual dysfunction, we refer to decreased libido, erectile dysfunction, decreased ejacula- tion and other ejaculation disorders. This knowledge has spurned interest in the potential use of phosphodiester- ase 5 (PDE-5) inhibitors in the treatment of symptomatic BPH [7,8]. Pathophysiology of lower urinary tract symptoms and benign prostatic hyperplasia Prostatic smooth muscle tone is under the influence of the autonomic nervous system. Thus, any pharmacologic agent that may affect the functioning of this system could alter resistance in smooth muscle tone. There are three main components to clinically significant BPH: static, dynamic and detrusor muscle components as outlined above. The dynamic component is associated with an increase in smooth muscle tone of the prostate. These smooth muscle cells contract under the influence of noradrenergic sympathetic nerves, thereby constrict- ing the urethra [9]. Prostatic tissue contains high levels of both alpha 1 and alpha 2 adrenoceptors – 98% of the alpha 1 adrenoceptors are associated with stromal elements of the prostate [10]. Thus, alpha 1 -receptor blockade relaxes smooth muscle, resulting in relief of bladder outlet obstruction that enhances urine flow [11]. Different subtypes of alpha 1 receptors have been identified, with alpha 1A being the predominant one. Two alpha 1A adre- noceptors generated by genetic polymorphism have been identified with different ethnic distributions but similar pharmacologic properties [12]. University of Melbourne, Departments of Surgery and Urology, Austin Hospital, Melbourne, Australia Correspondence to Associate Professor Damien M. Bolton, Director of Urology, Austin Health, 5/210 Burgundy Street, Heidelberg, Melbourne 3084, Australia Tel: +61 3 9457 4049; e-mail: damienmb@unimelb.edu.au Current Opinion in Urology 2009, 19:7–12 Purpose of review Phosphodiesterase 5 (PDE-5) inhibitors are established as first-line therapy in erectile dysfunction. There is emerging evidence that they may have a role in treating patients with lower urinary tract symptoms (LUTS) from benign prostatic hypertrophy. Recent findings All three commonly used PDE-5 inhibitors (sildenafil, vardenafil and tadalafil) appear to improve LUTS as measured by the International Prostate Symptom Score. However, to date, no change in urinary flow rates have been demonstrated. Summary Erectile dysfunction and LUTS frequently coexist in men of advancing age. There appears to be an emerging role for PDE-5 inhibitors as a treatment for both conditions. Further studies are required to elicit the exact mechanism of action in LUTS. Keywords benign prostatic hypertrophy, lower urinary tract symptoms, phosphodiesterase 5 inhibitors Curr Opin Urol 19:7–12 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins 0963-0643 0963-0643 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MOU.0b013e328316c357