Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: Pathophysiology and mechanism(s) of action

Andersson, Karl‐Erik; Groat, William C. de; McVary, Kevin T.; Lue, Tom F.; Maggi, Mario; Roehrborn, Claus G.; Wyndaele, Jean Jacques; Melby, Thomas; Viktrup, Lars

doi:10.1002/nau.20999

Cited by 207 publications

(227 citation statements)

References 127 publications

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“…Tadalafil has its therapeutic effects through beneficial actions on smooth muscle relaxation, smooth muscle and endothelial cell proliferation, nerve activity and tissue perfusion. 89 Significant improvement in IPSS after PDE5-inhibitor therapy compared with placebo was reported in all clinical studies with the magnitude of IPSS improvement comparable with those reported in previous a-blocker studies. Interestingly, none of the studies showed a significant effect of PDE5-I on peak urinary flow rate.…”

Section: Luts and Ed: Effects On Clinical Managementsupporting

confidence: 82%

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

2011

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There is strong evidence from multiple epidemological studies that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are correlated, independent of age or comorbidities as diabetes or hypertension. Although a direct causal relationship is not established yet, four pathophysio logical mechanisms can explain the relationship. These include alteration in nitric oxide bioavailability, a1-adrenergic receptor hyperactivity, pelvic atherosclerosis and sex hormones. This association has different clinical implications on the management of both disorders. Men seeking care for one condition should always be screened for complaints of the other condition. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. PDE5 inhibitors show promise as a future treatment for LUTS, either in conjunction with existing therapies or as a primary treatment. There may be a potential therapeutic role for testosterone in LUTS treatment in cases of testosterone deficiency that needs to be investigated. Much further investigation is required, but it is evident that the association between LUTS and ED is fundamental for future therapies and possible preventative strategies.

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Section: Luts and Ed: Effects On Clinical Managementsupporting

confidence: 82%

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

2011

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“…Bladder ischemia is caused by reduced bladder blood flow associated with aging, arteriosclerosis and BOO. Recent reports indicated a strong relationship of LUTS/BPH with metabolic syndrome and erectile dysfunction (ED) [22,23], and many studies demonstrated that PDE5i, agents used for the treatment of ED, also improved LUTS in patients with BPH [11][12][13]. The results of these studies implicate that LUTS/BPH are partially attributed to disturbance in the NO/cGMP pathway caused by reduced bladder blood flow, and that PDE5i could improve LUTS/BPH by activating the NO/cGMP pathway.…”

Section: Discussionmentioning

confidence: 99%

“…These basic studies are translated into clinical urology and PDE5i is Matsumoto S, et al, Effect of PDE3i treatment on female rat obstructed bladder -5 -used for treating male LUTS [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Chronic Treatment With Cilostazol, a Phosphodiesterase 3 Inhibitor, on Female Rat Bladder in a Partial Bladder Outlet Obstruction Model

Matsumoto

Watanabe

Hashizume

et al. 2014

Urology

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Tel; +81-166-68-2533, Fax; +81-166-68-2539, E-mail; matsums@asahikawa-med.ac.jp utnnin title Effect of PDE3i treatment on female rat obstructed bladder. Methods Twelve-week-old female Sprague-Dawley rats were divided into five groups; group 1 and 2, sham operated rats (each 4 rats); group 3-5, BOO rats (each 6 rats).Group 1 and 3 rats were given normal diet, group 2 and 5 rats were given high dose PDE3i diet, and group 4 rats were given low dose PDE3i diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO, the bladder was excised and dissected into four longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol and KCl was determined for each group.uestlts BOO induced a significant increase in bladder weight in group 3-5 compared with group 1 and 2. PDE3i treatment did not affect bladder weight in either sham or BOO rats.Contractile forces in response to EFS, carbachol and KCl in group 3 were about 20-40% of those in group 1. Contractile responses to EFS or KCl in PDE3i treated BOO rats were not significantly different from those in normal diet treated BOO rats. Only high dose of PDE3i treatment in BOO rats caused a statistically significant increase in the response to carbachol compared with normal diet treated BOO rats. ConcltsionsPDE3i has a small but significant protective effect on the contractile Matsumoto S, et al., Effect of PDE3i treatment on female rat obstructed bladder-3 -dysfunction induced by 4-weeks BOO in rats, although the increase in bladder mass was not altered. PDE3i could be a useful protection against contractile dysfunction of the obstructed bladder. Matsumoto S, et al., Effect of PDE3i treatment on female rat obstructed bladder -4 - IntroductionLUTS are highly prevalent among elderly men and women, and have a significant impact on the patients' quality of life. The cause of LUTS is multifactorial and includes BOO, bladder ischemia, autonomic sympathetic overactivity, and so on [1]. Increasing evidence has shown that ischemia and reperfusion are major etiologic factors in the progression of bladder dysfunction induced by BOO, and that part of the damage is due to the generation of free radicals and the resultant cellular and subcellular membrane peroxidation [1]. The importance of ischemia as an etiologic factor in bladder dysfunction has been supported by recent animal studies in which bladder ischemia was experimentally created by BOO, bladder overdistension and atherosclerosis [2][3][4][5][6][7]. The evidence has suggested that bladder ischemia causes significant bladder dysfunction and leads to decreased contractile responses of the bladder.  1 -blocker has been shown to have a protective effect on bladder function of the rat after BOO or bladder overdistension possibly through an improvement of bladder ischemia [6,7]. In clinical practice, 1 -blocker is widely used as a first-line treatment for male patients with LUTS that are associated with BOO due to BPH (LUTS/BPH). 1 -...

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“…[19] While LUTS is ultimately a multifactorial and multidimensional problem, similarities between the pathophysiological mechanisms of LUTS and ED include the nitric oxide-cyclic guanosine monophosphate (NO/ cGMP) pathway, RhoA/Rho-kinase signaling, pelvic ischemia, and autonomic adrenergic over activity. [19,20] These similarities may explain why PDE5 inhibitors such as tadalafil and sildenafil are successfully utilized in the treatment of BPH-related LUTS. Taken alone, PDE5 inhibitors reduce the International Prostate Score Symptoms scores by nearly three points compared with the scores using a placebo and demonstrate moderate synergy when taken in combination with α-blockers.…”

Section: Avanafilmentioning

confidence: 99%

“…Taken alone, PDE5 inhibitors reduce the International Prostate Score Symptoms scores by nearly three points compared with the scores using a placebo and demonstrate moderate synergy when taken in combination with α-blockers. [19,20] There is currently a lack of objectivity, however, pertaining to the effects of PDE5 inhibitors (i.e., tadalafil) on other quantifiable variables such as Q max . [19,21] The AUA does not include PDE5 inhibitors in its clinical guidelines for LUTS, but the European Association of Urology lists the class of medications under "new emerging drugs" for the treatment of male LUTS.…”

Section: Avanafilmentioning

confidence: 99%

Current use of phosphodiesterase inhibitors in urology

Hakky¹,

Jain²

2015

Turkish Journal of Urology

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The causes of male erectile dysfunction (ED) are quite variable and are now commonly divided into etiologies such as ischemia, smooth muscle damage, or altered blood flow. Although varying rates of ED have been reported in literature, the number of men with ED is projected to increase worldwide by 2025 to approximately 322 million. Since the introduction of phosphodiesterase 5 (PDE5) inhibitors, there has been a paradigm shift in the treatment of ED because PDE5 inhibitors address a broad spectrum of etiologies for ED. Today, the American Urological Association recommends the use of three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) as a first-line therapy for the treatment of ED. This review evaluates the pharmacological mechanism of PDE5 inhibitors along with the impact and use of sildenafil, vardenafil, tadalafil, and avanafil. By increasing intracellular cGMP levels, PDE5 inhibitors have been shown to be effective in the treatment of ED. Through their effects on other cellular signaling pathways, PDE5 inhibitors have the potential for treating other urologic conditions as well. The use of PDE5 inhibitors can also be combined to produce a synergistic effect in conditions such as male hypogonadism and benign prostatic hyperplasia in addition to ED.

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Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: Pathophysiology and mechanism(s) of action

Cited by 207 publications

References 127 publications

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

Effects of Chronic Treatment With Cilostazol, a Phosphodiesterase 3 Inhibitor, on Female Rat Bladder in a Partial Bladder Outlet Obstruction Model

Current use of phosphodiesterase inhibitors in urology

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