Latest Evidence on the Use of Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

Gacci, Mauro; Andersson, Karl Erik; Chapple, Christopher R.; Maggi, Mario; Mirone, Vincenzo; Oelke, Matthias; Porst, Hartmut; Roehrborn, Claus G.; Stief, Christian G.; Giuliano, François

doi:10.1016/j.eururo.2015.12.048

Cited by 112 publications

(96 citation statements)

References 57 publications

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“…These agents have been increasingly utilized for the treatment of LUTS/BPH. By increasing cellular levels of cGMP these medications have been shown to increase LUT oxygenation, induce smooth muscle relaxation in the prostate and bladder neck, decrease prostatic stromal proliferation, and reduce afferent nerve activity from the LUT (56). These agents have been shown to reduce prostatic inflammation, particularly in men with the metabolic syndrome (57,58).…”

Section: Effect Of Bph Treatments On Ejaculatory Functionmentioning

confidence: 99%

Ejaculatory dysfunction in the treatment of lower urinary tract symptoms

DeLay

Nutt

McVary

2016

Transl. Androl. Urol.

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The link between lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and sexual dysfunction is well established. Sexual dysfunction can encompass both ejaculatory dysfunction (EjD) and erectile dysfunction (ED). Ejaculatory dysfunction can consist of premature ejaculation, delayed ejaculation, retrograde ejaculation, anejaculation, decreased force of ejaculation and pain upon ejaculation. The impact of different medical and surgical therapies on ejaculatory function will be reviewed. We reviewed the various categories of LUTS treatment including the canonical epidemiology and pathophysiology as well as the surgical and medical treatments for LUTS/BPH. We note that most surgeries and several medical treatments have a certain but ill-defined negative impact on ejaculatory function. Several MISTs and selected medical therapies appear to have little impact on EjD. Both EjD and BPH are very common disorders in men under the care of an urologist. It is well documented that there is a clinical association between these two entities. Unfortunately many of the medical treatments and almost all surgical treatment impact the ejaculatory function of the patient. The surgical treatment of BPH often leads to retrograde ejaculation while medical treatment leads to anejaculation.

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Section: Effect Of Bph Treatments On Ejaculatory Functionmentioning

confidence: 99%

Ejaculatory dysfunction in the treatment of lower urinary tract symptoms

DeLay

Nutt

McVary

2016

Transl. Androl. Urol.

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“…The entire lower urinary tract (LUT) expresses PDE5 (Fibbi et al, ; Filippi et al, ), and studies support the use of PDE5 inhibitors to reduce LUTS, utilizing the NO/cGMP pathway on several potential targets. These include increasing LUT oxygenation, decreasing afferent nerve activity, negatively regulating proliferation of LUT stroma and LUTS‐related inflammation (Gacci et al, ). The ability of sildenafil to relax smooth muscle directly has also been demonstrated, where sildenafil‐induced relaxation of human detrusor strips is significantly decreased using a soluble GC inhibitor to block the formation of cGMP (Oger et al, ).…”

Section: Introductionmentioning

confidence: 99%

Influence of sildenafil on the purinergic components of nerve‐mediated and urothelial ATP release from the bladder of normal and spinal cord injured mice

Chakrabarty

Ito

Ximenes

et al. 2019

British J Pharmacology

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Background and purpose PDE inhibitors such as sildenafil alleviate lower urinary tract symptoms; however, a complete understanding of their action on the bladder remains unclear. We are investigating the effects of sildenafil, on post and preganglionic nerve‐mediated contractions of the mouse bladder, and neuronal and urothelial ATP release. Experimental approach Bladders were used from young (12 weeks), aged (24 months), and spinal cord transected (SCT), mice, for in vitro contractility experiments. An arterially perfused in situ whole mouse model was used to record bladder pressure. Nerve‐mediated contractions were generated by electrical field stimulation (EFS) of postganglionic nerve terminals or the pelvic nerve. ATP release during EFS in intact detrusor strips, and during stretch of isolated mucosa strips, was measured using a luciferin‐luciferase assay. Key results Sildenafil (20 μM) inhibited nerve‐mediated contractions in young mice, with an increase in f 1/2 values in force–frequency relationships, demonstrating a greater effect at low frequencies. Sildenafil reduced the atropine‐resistant, purinergic component of nerve‐mediated contractions, and suppressed neuronal ATP release upon EFS in vitro. Sildenafil reduced the preganglionic pelvic nerve stimulated bladder pressure recordings in situ; comparable to in vitro experiments. Sildenafil reduced stretch‐induced urothelial ATP release. Sildenafil also relaxed nerve‐mediated contractions in aged and SCT mice. Conclusion and implications Sildenafil has a greater effect on the low‐frequency, purinergic‐mediated contractions and suppresses neuronal ATP release. In addition, sildenafil reduces stretch‐induced urothelial ATP release. These results demonstrate a novel action of sildenafil to selectively inhibit ATP release from nerve terminals innervating detrusor smooth muscle and the urothelium.

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“…Whereas the role of PDE5 inhibitors in vasculature has already been discussed (20), nothing is known about the functional relevance of PDE5 inhibitors in prostate ducts with their large amount of PDE5-expressing SMCs. Therefore, prostate ducts were isolated and investigated by our life-imaging approach ex vivo (Fig.…”

Section: Isolated Prostate Glands Show Spontaneous Contractions That mentioning

confidence: 99%

“…In their most recent review, Gacci et al (20) describe a series of cGMP/PDE5 actions in LUTS and BPH such as modulation of oxygenation, inflammation, proliferation, and nerve activity. However, the most established mechanism of action of PDE5 inhibitors is smooth muscle relaxation leading to reduced muscle tone (20,21). PDE5 inhibitors have been shown to relax isolated prostate strips in numerous species (14,(21)(22)(23).…”

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confidence: 99%

Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects

et al. 2018

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Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques-notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/ in situ hybridization-compatible tissue-hydrogel (CLARITY) and time-lapse imaging-and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate's contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.-Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.

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Latest Evidence on the Use of Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

Cited by 112 publications

References 57 publications

Ejaculatory dysfunction in the treatment of lower urinary tract symptoms

Ejaculatory dysfunction in the treatment of lower urinary tract symptoms

Influence of sildenafil on the purinergic components of nerve‐mediated and urothelial ATP release from the bladder of normal and spinal cord injured mice

Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects

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