Lower urinary tract symptoms
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Lower Urinary Tract Symptoms, Benign Prostatic Hyperplasia, and Sexual DysfunctionJonathan K. Park, BA, Tobias S. Köhler, MD, MPH,and Kevin T. McVary, MDCorresponding authorKevin T. McVary, MDDepartment of Urology, Northwestern University Medical School, Tarry 16-749, 303 East Chicago Avenue, Chicago, IL 60611, USA.E-mail: k-mcvary@Current Bladder Dysfunction Reports 2008, 3:233–240Current Medicine Group LLC ISSN 1931-7212Copyright © 2008 by Current Medicine Group LLCPreviously viewed as independent processes, sexual dys-function (SD) and lower urinary tract symptoms (LUTS) frequently associate and signifi cantly detract from overall quality of life for men. Analysis of historic and emerging literature using some of the Bradford-Hill criteria argues causality between the two disease processes, with most data focusing on the interplay between LUTS and erectile dysfunction. Understanding of the relationship between SD and LUTS is crucial given the current societal age demographics leading to an increased pool of affected patients. Additional information on risk factors for either disease could potentially improve patient screening, and many currently available treatments (medical and surgical) for SD impact LUTS and vice versa.IntroductionLower urinary tract symptoms (LUTS) and sexual dysfunc-tion (SD) are two highly prevalent disease processes that affect aging men [1,2]. Previously viewed as independent processes, these diseases frequently associate and signifi-cantly impact overall quality of life for men [2,3]. Almost all accepted therapies for LUTS (surgical or medical) can impact some aspect of sexual health, and treatments for SD can also affect LUTS [4,5]. The current literature describing the interplay of LUTS and SD predominantly focuses on erectile dysfunction (ED) but can also relate to ejaculatory dysfunction (EJD) [5]. Furthermore, the link between LUTS and sexual function is not restricted to men, as there appears to be a link between female sexual dysfunction and LUTS or incontinence [6–8].In the context of an increasingly aging population and the current environment of expanding indications for intervention, a more in-depth understanding of the rela-tionship between LUTS and sexual function is needed. Because the link between LUTS and sexual function seems to affect men and women, this knowledge will benefi t all patients and health care professionals.To further understand the relationship between LUTS and ED, one must apply some of the Bradford-Hill criteria to the mounting body of epidemiologic evidence to sepa-rate causal from noncausal explanations. Cross-sectional epidemiologic data, case-control reports, and cohort studies grounded by supportive plausible mechanisms are assessed to further comprehend the epidemiologic evidence. Data are examined for the strength of associa-tion through assessing RR, consistency between studies (replication of fi ndings), dose-response effect, and the presence of a temporal relationship between index disease development and progression or cessation. Most impor-tantly, the observed epidemiologic data must not only account for alternative explanations, such as chance, bias, and confounders, but must also be biologically plausible. The current review summarizes our understanding of the epidemiologic relationship between LUTS and sexual dys-function and offers four potential biologic mechanisms to explain these interactions.The Epidemiologic Relationship Between LUTS and Sexual DysfunctionAge is widely recognized as one of the most important risk factors for SD. The preponderance of epidemio-logic data linking LUTS to SD pertains to ED but also includes EJD and female SD. Men in their 50s have a twofold increase in their RR of ED compared with men in their 40s [9•]. Men are increasingly burdened with ED as time progresses, and most of these men have advanced symptoms. These fi ndings were demonstrated by the Massachusetts Male Aging Study (MMAS), which showed that 52% of men ages 40 to 70 have234 Male Voiding Dysfunctionsome degree of ED and also that two thirds of these men manifest moderate to severe symptoms [1].Paralleling the trend with ED, the prevalence of gross, potentially clinically signifi cant benign prostatic hyperpla-sia (BPH) lesions positively correlates with increasing age. Studies show that BPH increases progressively from the fourth (8%) through the eighth (82%) decade of life [10]. Further supporting these studies, the Baltimore Longitudi-nal Study of 1057 men demonstrated that the cumulative prevalence of a history and physical examination–based diagnosis of LUTS or BPH voiding dysfunction increased progressively from 26% to 79% from the fi fth to eighth decade of life [11]. These studies demonstrate that age is a signifi cant risk factor for BPH and sexual dysfunction.Although the aforementioned studies assessed the link between LUTS and SD in men, several studies also documented a comparable prevalence of similar LUTS in aging women, challenging the idea that prostatic change is the cardinal cause of LUTS [12,13]. However, given the potential role of the central nervous system and the blad-der in LUTS, this seemingly surprising relationship seen in women does not weaken the putative argument for a relationship between LUTS and ED [14].Having demonstrated the impact of age on LUTS and sexual function, the next logical step is to assess the possibil-ity of a relationship between LUTS and SD independent of age. One of the fi rst studies to investigate the role between sexual function and LUTS used a cross-sectional, com-munity-based survey and noted that sexual satisfaction correlated negatively with increasing age and LUTS [15]. The RR of ED stratifi ed by the International Prostate Symp-tom Score (IPSS) showed a 3.3-fold increase for symptom scores greater than 19 compared with IPSS scores of zero. Several cross-sectional, questionnaire-based studies have since shown an increased RR of ED in men who also had LUTS [16–18]. However, these studies did not control for confounders such as age through multivariate analysis.Building on these early results, the Multinational Survey of the Aging Male (MSAM-7) study revealed a strong asso-ciation between IPSS score and the level of sexual activity and International Index of Erectile Function (IIEF) score [2]. This study is important, as it demonstrated that the associa-tion between LUTS and ED persisted even after controlling for age and other comorbidities known to impact sexual function, such as diabetes mellitus. This study also empha-sized that sexual activity is common in most men over age 50 and contributes heavily to quality of life.Multiple other reports confi rmed the independent association between ED and LUTS. In Europe, Val-lancien et al. [19] used the IPSS and Danish Prostatic Symptom Score sex questionnaires to evaluate 1274 men older than age 45 who suffered from LUTS. The inci-dence of ED rose from 55% in men with mild LUTS to 70% in men suffering from severe LUTS. After multiple regression analysis, ED was independently associated with the presence of LUTS.Further studies demonstrated that the LUTS–ED independent relationship was upheld even in different demographic populations. Terai et al. [20] used the IPSS and IIEF questionnaires to evaluate 2084 Japanese men undergoing routine health screening. Increasing severity of LUTS was associated with increased incidence of ED, and this relationship persisted even after controlling for age.Other studies have controlled for age and common medical comorbidities. McVary et al. [21] reported a statistically signifi cant association between baseline American Urology Association (AUA) Symptom Index and the various domains of sexual function, such as erec-tile capability, libido, ejaculation, and overall satisfaction with sexual life. There was also signifi cant association between maximum fl ow rate (Qmax) and the various sex-ual function domains, such as libido, erectile capability, ejaculation, problem assessment, and overall satisfaction with sexual life (P < 0.001 for each domain). The rela-tionship between Qmax, total prostate volume, transition zone volume, and ED noted in the Medical Therapy of Prostatic Symptoms (MTOPS) study is crucial, as it links ED symptoms with more fundamental physiologic and biologic measures of bladder and prostate dysfunction. Importantly, statistical signifi cance remained even after performing a multivariate analysis with excellent subject characterization that controlled for ED comorbidities such as age, partner status, marital status, hypertension, lipid disorders, and diabetes. Also, the duration of LUTS associated very strongly with erectile function, problem assessment, and the overall satisfaction with sexual life (P < 0.01). These results strongly support the idea that the association between LUTS and sexual dysfunction is independent of the usual comorbidities.The preponderance of the evidence for studies between LUTS and ED fulfi ll the Hill’s Causality criteria for strength of association, internal consistency, and dose-response effects (worse LUTS equals worse ED) (Table 1).The issue of an alternate explanation to account for the LUTS–ED association appears to be satisfi ed by several large studies that use multiple regression analyses (and thus minimize confounding), after which the LUTS–ED rela-tionship remains signifi cant [2,19–22]. The requirement of LUTS–ED temporality had not been satisfi ed until recently, with the publication of three studies in which the adminis-tration of a phosphodiesterase (PDE) inhibitor resulted in an immediate improvement of LUTS [4,23•,24,25].As demonstrated, LUTS signifi cantly correlates with ED; however, the MSAM-7 additionally noted that LUTS also correlates with EJD. Moreover, the study showed that the severity of ejaculatory problems increases with wors-ening LUTS [2]. The cumulative results of the MSAM-7 suggest that although older men still actively engage in sexual activity, the severity of LUTS affects their ability to perform, independent of other risk factors.Several medical and surgical treatments for LUTS nega-tively impact ejaculatory function. The 2003 AUA BPHLUTS, BPH, and Sexual Dysfunction Park et al.235guidelines reported EJD for tamsulosin to be 10%; inter-estingly, the highest rates reported for other drugs in the α-blocker class, such as doxazosin and terazosin, were 0% and 1%, respectively [26]. A recent study revealed that the most common aspect of EJD associated with tamsulosin is not retrograde ejaculation, but decreased volume of ejacu-late, followed by anejaculation [27]. In contrast, the samestudy reported no anejaculation with alfuzosin, further236 Male Voiding Dysfunctionsuggesting that the effect is unique to tamsulosin within the α-blocker class. Rates of EJD for another commonly used BPH medication, fi nasteride, are reported at 4% [26].The surgical treatment for LUTS also impacts EJD. The frequency of EJD was reported at 65% with transurethral resection of prostate (TURP); 5% to 16% with transure-thral wave thermotherapy (TUMT); 4% with transurethral needle ablation (TUNA); and 2% for sham controls [26]. These surgical options correlate with EJD and, to a varying extent, with ED. ED incidence has been reported as 10% with TURP, 1% with TUMT, 3% for TUNA, and 2% for sham controls [26]. Although most studies report worsen-ing ED with TURP compared with less invasive treatments, one study reported amelioration of ED following TURP and no signifi cant differences in erectile function between TURP and laser therapy [28].Sexual dysfunction following non-LUTS surgery is common. Elevated rates of SD have occurred following open aortic aneurysm repair, colorectal resection, and orthopedic joint replacement surgery [29–31]. These studies highlight the possibility that surgical procedures in general may result in SD. Alternatively, those with baseline ED or other sexual disorders may not have had a chronologic event with which to associate the onset of their disease, thus spuriously indicting their operation as a potential cause. These scenarios provide a conceptual rationale for possible prior overestimation of sexual dys-function following LUTS surgery.While various investigators have examined the link between LUTS and SD in men, studies have also exam-ined a potential link in women [6–8]. Salonia et al. [6] compared women with and without LUTS/urinary incontinence (UI) and found that women with urinarycomplaints noted signifi cantly more sexual dysfunction than women lacking urinary complaints. Furthermore, a study by Özel et al. [7] suggested that the presence of pelvic organ prolapse exacerbated SD in women with UI. In 2008, Dalpiaz et al. [8] sought to further develop the link between LUTS/UI and female SD. Although the rea-son for this link remains unclear, the investigators assert that the cause is likely multifactorial and may include a psychological basis (namely, the fear of urinary leakage during intercourse).Biological Plausibility: Mechanisms of Interaction Between LUTS and EDTo support the epidemiologic evidence of a relationship between LUTS and sexual dysfunction, a biologically sen-sible mechanism explaining the interaction is required. To date, possible biologic interrelationships between LUTS and ED fall into four related physiologically relevant theories (Fig. 1).NOS/NO levels decreased or altered in the bladder, prostate, and penile smooth muscleThis hypothesis asserts that reduced production of nitric oxide synthase (NOS) and/or nitric oxide (NO) in the pel-vis (bladder, penis, and prostate) explains the link between ED and LUTS [32]. This theory incorporates the nitrergic innervation–smooth muscle cell relaxation molecular mechanism of ED. It also elegantly unifi es both disease processes because it is reported that NOS/NO production of the prostate is reduced in BPH (transition zone) com-pared with normal prostate tissue. Prostate tissue levels of NOS/NO are reduced in BPH progression, which then reduces prostatic tone relaxation, leading to LUTS [33]. The LUTS–ED, NOS/NO theory is further supported by the characterization and functional relevance of cyclic nucleotide PDE isoenzymes of the human prostate [34], the most common PDEs found in prostate tissue being PDE type 4 and PDE type 5.It was shown recently that PDE5 mRNA is found in greatest quantity in the human corpora cavernosa (~ 10-fold higher); however, PDE5 mRNA was also found in order of decreasing magnitude over the vas deferens, prostate, epi-didymis, bladder (immunolocalized to vascular endothelium and muscle fi bers only), testis, and kidney [35]. Conversely, rat PDE5 is expressed highest in the bladder, about 10-fold higher than rat corpora cavernosa, followed in decreas-ing prevalence by the vas deferens, prostate, kidney, testis, and epididymis [36]. All PDE5 inhibitors inhibited cGMP catabolizing activity in human bladder cells and rat bladder strips and induced a consistent antiproliferative and relax-ant effect, supporting the idea of the role of NO/NOS in the urinary system.To further characterize the pelvic PDE profi le, Fawcett et al. [37] performed Northern and RNA dot blots forPDE11A gene expression and isolated its presence in testes,Figure 1. Potential linkages in the pathophysiology among the four proposed mechanisms for the association between lower urinary tract symptoms and erectile dysfunction. A—agonist; DAG—dia-cylglycerol; IP 3—inositol triphosphate; MLC—myosin light chain; MLC-P—myosin light chain-phosphatase; PKC—protein kinase C; PLC—phospholipase C; R—receptor; SR—sarcoplasmic reticulum.LUTS, BPH, and Sexual Dysfunction Park et al. 237skeletal muscle, and the prostate. Type 11A protein abun-dance was greatest in the prostate compared with other organs. Although the role of prostatic PDE11A is unknown, its relatively low abundance in the smooth muscle makes its pivotal role in the LUTS–ED relationship less likely. Thus, based on these studies, it is apparent that PDE5 may have a signifi cant role in the pathogenesis of LUTS and ED.With the apparent biologic basis of a role for PDE in the prostate and bladder, the next logical step is to translate this hypothesis into a useful clinical tool. The concept that PDE5 inhibitors could be used to improve LUTS is provocative, fueling three recent studies seeking to elucidate the relationship between these two important diseases in a randomized, placebo-controlled fashion [23•,24,25]. McVary et al. [4,24] performed a 12-week, double-blinded, placebo-controlled study of sildenafi l in 369 men 45 years old or older who had IIEF scores less than 26 and IPSS scores greater than 11. Compared with placebo, patients in the sildenafi l group demonstrated improved IIEF scores and emotional well-being, as well as greater treatment satisfaction (P < 0.0001).Stief et al. [25] performed a study on 221 men 45 to 64 years old who had an IPSS greater than 11 at time of random-ization before 8 weeks of treatment with 10 mg of vardenafi l twice a day versus placebo [25]. After 8 weeks of treatment, the total IPSS score in the vardenafi l group improved signifi -cantly compared with placebo (P = 0.0013).The study by McVary et al. [23•] with tadalafi l likely yields the most reliable fi ndings given its trial design. The magnitude of IPSS improvement observed compared similarly with results reported in α-blocker studies. Taken together, these three studies consistently demonstrated tem-porality between LUTS and ED. As for the specifi c site of action of the PDE5 inhibitors, a recent study in spinal cord injury patients demonstrated improvements in maximum cystometric capacity and increase in detrusor overactivity volume value, suggesting that the site of action by PDE5 inhibitors in alleviating LUTS is the bladder [38].Autonomic hyperactivity and metabolic syndrome effects on LUTS, prostate growth, and EDThe autonomic nervous system (ANS) plays an important role in the control of prostate growth and differentiation [39]. Using a rat model, McVary et al. [39] demonstrated that the ANS provides an environment that induces rat prostatic growth, whereas its absence leads to glandular regression. These fi ndings were supported by additional animal studies using spontaneously hypertensive rats (SHR) that developed increased autonomic activity, prostate hyperplasia, and ED [40,41]. Following brief but aggressive hypertension treat-ment, erectile function improved [41]. These effects may be related to improvement in structurally based vascular resis-tance within the penis and the decrease in responsiveness of α1-adrenoceptor–mediated erectolytic signaling.The metabolic syndrome, which includes glucose intolerance, hypertension, hyperlipidemia, and centralobesity, also incorporates autonomic hyperactivity. It is an attractive theory because it explains the association of the metabolic syndrome with LUTS and ED and also links established clinical physiologic fi ndings of LUTS, BPH, and ED with established basic science evidence [32]. However, it remains unclear whether the increase in LUTS or ED is the result of a central increase in sensitiv-ity to peripheral signals, or a consequence of an alteration in the function of the bladder and penis that generates increased central activation. Autonomic hypersensitivity may also impact smooth muscle relaxation and penile responsiveness through increasing sympathetic tone. The encouraging results of early laboratory research warrant future studies to further elucidate the precise mechanism linking autonomic hyperactivity to LUTS and ED.Animal studies suggesting that autonomic hyperactiv-ity contributes to increased prostate growth are bolstered by epidemiologic investigations linking the clinical diag-nosis of BPH with increased autonomic tone. The ANS is intimately involved in voiding mechanisms, and recent evidence shows that ANS hyperactivity is signifi cantly associated with BPH signs and symptoms, as well as the most commonly used measures of LUTS (AUA symptom score and BPH Impact Index score) [42]. As a result, fur-ther knowledge of autonomic hyperactivity will provide a better understanding of the pathophysiology of BPH, prostate growth, and ED. Thus, ANS hyperactivity is a plausible biological theory that potentially helps to explain the epidemiologic linkage between ED and LUTS.The alternate pathway: Rho-kinase activationInvestigators have suggested that the so-called alternate pathways of smooth muscle relaxation and contraction may be responsible for the relationship between ED and bladder outlet obstruction (BOO) [32]. Phosphorylation and dephosphorylation of myosin light chain (MLC) are the primary mechanisms of regulating smooth muscle contractility and are in part modulated by MLC phos-phatase (MP). It has been shown that MP is regulated by the protein Rho-kinase. Rho-kinase inhibits MP, lead-ing to an elevation of MLC phosphorylation without an accompanying increase in calcium concentration, a phe-nomenon referred to as calcium sensitization of smooth muscle [43]. Given the intricate role of Rho-kinase in smooth muscle contraction, it is not surprising that Rho-kinase is associated with increased bladder tone and prostatic smooth muscle proliferation, leading to BOO (Fig. 2A, Fig. 2B) [44•].Given the role of Rho-kinase in BOO, it is a potential target for drug inhibitor therapy, possibly by reducing the effects of BPH [44•]. In the previously mentioned SHR model, it was also found that Rho-kinase inhibitors sig-nifi cantly suppressed bladder overactivity [45]. Different isoforms of Rho-kinase have been characterized recently, suggesting that alterations in the isoform profi le may be part of a molecular mechanism of bladder adaptation238 Male Voiding Dysfunctionfollowing BOO [46]. Further isoform characterization will aid efforts to target a specifi c Rho-kinase variant for treatment of LUTS.The suggestion that BOO induces ED via an upreg-ulation of Rho-kinase in the penis has experimental merit. Multisystem dysfunction of Rho-kinase may also occur, leading to both LUTS and ED. Evidence from a rabbit study demonstrated increased basal corpus cav-ernosum smooth muscle (CCSM) tone associated with an elevated level of smooth muscle myosin phosphory-lation in BOO rats compared with control rats [47]. Furthermore, Rho-kinase was higher in the CCSM of the BOO group than that of the control group [48]. This study also illustrated that Rho-kinase inhibitors produce CCSM relaxation, reinforcing the idea that Rho-kinase is involved in the pathophysiology of both LUTS and ED and that it may also serve as a therapeu-tic target for both disease processes.Pelvic atherosclerosis as a mechanism for LUTS and ED An additional hypothesis causatively linking LUTS andED is diffuse atherosclerosis of the prostate, penis, and bladder [49]. The proponent theorized that several ED risk factors (hypertension, smoking, hypercholesterol-emia, and diabetes mellitus) also impact LUTS and BPH.The hyperlipidemic rabbit model demonstratesincreased prostate weight, bladder overactivity, and ED after being fed a high-fat diet [50]. Potential mechanisms include hypoxia-induced overexpression of transforming growth factor-β1 and altered prostanoid production. Penile ischemia results in smooth muscle loss and ED. An analogous loss of smooth muscle in the bladderwould decrease compliance and worsen LUTS. Similarly, bladder ischemia resulting from BOO or pelvic vascular disease can induce bladder smooth muscle loss, result-ing in collagen deposition and fi brosis, as well as loss of compliance, hyperactivity, and impaired contractility [50]. Loss of smooth muscle in the prostate causes a less distensible urethra, increased fl ow resistance, decreased urinary fl ow rate, and worsening LUTS. The pelvic ath-erosclerosis theory holds appeal because it integrates the other LUTS/ED theories, in that pelvic ischemia may induce ANS hyperactivity, reduce NOS expression, and upregulate Rho-kinase [3].ConclusionsLUTS and sexual dysfunction are highly prevalent in aging men. It is well established that LUTS and SD inde-pendently reduce quality of life. In combination, these two clinical entities logically compound life distress.The literature supporting an age- and comorbidity-independent association between LUTS and SD is strong, consistent, and demonstrates a dose response. The link between LUTS and ED has biologic plausibility given the four leading theories of how these diseases interrelate. It is possible that these theories collectively contribute to theoverall pathogenesis of LUTS and ED.Recent studies showing a clear improvement in LUTS with the use of effective ED treatment of PDE5 inhibitors demonstrate the strongest evidence to date that these two disease processes are temporally and causally related, notsimply coincidental.Understanding the relationship between SD and LUTS is essential because additional information on risk factors for either disease could be important for patient screen-ing, population demographics reveal an increasing pool of affected men, and many currently available treatments for one disease affect the other [4,5].Establishing the evolving relationship of LUTS and SD will allow further insight into the etiology of LUTS. Using PDE inhibitors as prophylaxis for LUTS, or as a primary treatment for the LUTS/overactive bladder, seems a viable future possibility. Furthermore, treatment of LUTS with PDE inhibitors could potentially be used to treat LUTS in female patients.Figure 2. A and B , The role of Rho-kinase in smooth muscle relaxation and erectile dysfunction (ED). LUTS—lower urinary tract symptoms;MLC—myosin light chain; MLC-P—myosin light chain-phosphatase; NO—nitric oxide; NOS—nitric oxide synthase.LUTS, BPH, and Sexual Dysfunction Park et al.239DisclosuresDr. McVary is consultant for Pfi zer; a consultant for, speaker for, and recipient of grant support from Eli Lilly and Company; a speaker for and recipient of grant support from GlaxoSmithKline; and a speaker for and recipient of grant support from Sanofi. No other potential confl icts of interest relevant to this article were reported. References and Recommended ReadingPapers of particular interest, published recently,have been highlighted as:• Ofimportance•• Of major importance1. Feldman HA, Goldstein I, Hatzichristou DG, et al.:Impotence and its medical and psychosocial correlates:results of the Massachusetts Male Aging Study. J Urol 1994,151:54–61.2. Rosen R, Altwein J, Boyle P, et al.: Lower urinary tractsymptoms and male sexual dysfunction: the multinationalsurvey of the aging male (MSAM-7). Eur Urol 2003,44:637–649.3. McVaryKT:Erectile dysfunction and lower urinary tract symptoms secondary to BPH. Eur Urol 2005, 47:838–845. 4. McVary KT, Monnig W, Camps JL Jr, et al.: Sildenafi l citrateimproves erectile function and urinary symptoms in menwith erectile dysfunction and lower urinary tract symptomsassociated with benign prostatic hyperplasia: a randomized,double-blind trial. J Urol 2007, 177:1071–1077.5. LeporH:Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. TamsulosinInvestigator Group. Urology 1998, 51:892–900.6. Salonia A, Zanni G, Nappi RE, et al.: Sexual dysfunctionis common in women with lower urinary tract symptomsand urinary incontinence: results of a cross-sectionalstudy. Eur Urol 2004, 45:642–648; discussion 648.7. Özel B, White T, Urwitz-Lane R, Minaglia S: The impactof pelvic organ prolapse on sexual function in womenwith urinary incontinence. Int Urogynecol J Pelvic FloorDysfunct 2006, 17:14–17.8. Dalpiaz O, Kerschbaumer A, Mitterberger M, et al.: Femalesexual dysfunction: a new urogynaecological research fi eld.BJU Int 2008, 101:717–721.9.• McVaryKT:Clinical practice. Erectile dysfunction. N Engl J Med 2007, 13, 357:2472–2481.This review offers an excellent overview of ED pathophysiologyand treatment and recommendations for clinical use to aid patient evaluation and management.10. Berry SJ, Coffey DS, Walsh PC, Ewing LL: The developmentof human benign prostatic hyperplasia with age. J Urol 1984,132:474–479.11. Guess HA, Arrighi HM, Metter EJ, Fozard JL: Cumu-lative prevalence of prostatism matches the autopsyprevalence of benign prostatic hyperplasia. Prostate1990, 17:241–246.12. Chai TC, Belville WD, McGuire EJ, Nyquist L: Specifi cityof the American Urological Association voiding symptomindex: comparison of unselected and selected samples ofboth sexes. J Urol 1993, 150:1710–1713.13. GrayhackJT:Benign prostatic hyperplasia. The scope of the problem. Cancer 1992, 70:275–279.14. Andersson KE, Gratzke C: Pharmacology of alpha1-adre-noceptor antagonists in the lower urinary tract and centralnervous system. Nat Clin Pract Urol 2007, 4:368–378.15. Macfarlane GJ, Botto H, Sagnier PP, et al.: The relationshipbetween sexual life and urinary condition in the Frenchcommunity. J Clin Epidemiol 1996, 49:1171–1176.16. Braun MH, Sommer F, Haupt G, et al.: Lower urinary tractsymptoms and erectile dysfunction: co-morbidity or typical“Aging Male” symptoms? Results of the “Cologne MaleSurvey.” Eur Urol 2003, 44:588–594.17. Blanker MH, Bohnen AM, Groeneveld FP, et al.: Correlatesfor erectile and ejaculatory dysfunction in older Dutchmen: a community-based study. J Am Geriatr Soc 2001,49:436–442.18. Moreira ED Jr, Lisboa Lobo CF, Villa M, et al.: Prevalenceand correlates of erectile dysfunction in Salvador, north-eastern Brazil: a population-based study. Int J Impot Res2002, 14:S3–S9.19. Vallancien G, Emberton M, Harving N, van MoorselaarRJ: Sexual dysfunction in 1274 European men suffer-ing from lower urinary tract symptoms. J Urol 2003,169:2257–2261.20. Terai A, Ichioka K, Matsui Y, Yoshimura K: Association oflower urinary tract symptoms with erectile dysfunction inJapanese men. Urology 2004, 64:132–136.21. McVary KT, Foley JP, Slawin KM, et al.: The long termeffects of doxazosin, fi nasteride, and the combination onsexual function in men participating in the MTOPS Trial[abstract 1194]. J Urol 2004, 171:315.22. Elliott SP, Gulati M, Pasta DJ, et al.: Obstructive lowerurinary tract symptoms correlate with erectile dysfunction.Urology 2004, 63:1148–1152.23.• McVary KT, Roehrborn CG, Kaminetsky JC, et al.: Tadala-fi l relieves lower urinary tract symptoms secondary tobenign prostatic hyperplasia. J Urol 2007, 177:1401–1407. This study is of special interest in that it demonstrated improve-ment of LUTS (comparable to α-blocker studies) following use of PDE-5 inhibitor therapy. In doing so, it solidifi ed the temporality between LUTS and ED.24. McVary KT, Kaufman J, Young JM, Tseng LJ: Sildenafi lcitrate improves erectile function: a randomised double-blind trial with open-label extension. Int J Clin Pract 2007,61:1843–1849.25. Stief CG, Porst H, Neuser D, et al.: A randomised, placebo-controlled study to assess the effi cacy of twice-dailyvardenafi l in the treatment of lower urinary tract symptomssecondary to benign prostatic hyperplasia. Eur Urol 2008,53:1236–1244.26. AUA Practice Guidelines Committee: AUA guidelineon management of benign prostatic hyperplasia (2003).Chapter 1: diagnosis and treatment recommendations.J Urol 2003, 170:530–547.27. Hellstrom WJ, Sikka SC: Effects of acute treatment withtamsulosin versus alfuzosin on ejaculatory function innormal volunteers. J Urol 2006, 176:1529–1533.28. Brookes ST, Donovan JL, Peters TJ, et al.: Sexualdysfunction in men after treatment for lower urinary tractsymptoms: evidence from randomised controlled trial.BMJ 2002, 324:1059–1061.29. Jimenez JC, Smith MM, Wilson SE: Sexual dysfunction inmen after open or endovascular repair of abdominal aorticaneurysms. Vascular 2004, 12:186–191.30. Jayne DG, Brown JM, Thorpe H, et al.: Bladder andsexual function following resection for rectal cancer ina randomized clinical trial of laparoscopic versus opentechnique. Br J Surg 2005, 92:1124–1132.31. Nordentoft T, Schou J, Carstensen J: Changes in sexualbehavior after orthopedic replacement of hip or knee inelderly males—a prospective study. Int J Impot Res 2000,12:143–146.32. McVary KT, McKenna KE: The relationship betweenerectile dysfunction and lower urinary tract symptoms:epidemiological, clinical, and basic science evidence.Curr Urol Rep 2004, 5:251–257.33. Bloch W, Klotz T, Loch C, et al.: Distribution of nitricoxide synthase implies a regulation of circulation, smoothmuscle tone, and secretory function in the human prostateby nitric oxide. Prostate 1997, 33:1–8.。
