Purpose
To review the role of a persistent prostatic inflammatory status (PIS) in the development and progression of benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms ...(LUTS) and which medical therapies approved for LUTS/BPH may reduce persistent PIS.
Methods
Literature search in PubMed up to July 2019.
Results
The cause of histologically defined persistent PIS or chronic prostatic inflammation is multifactorial. It is evident in many men with LUTS/BPH, particularly in older men and in men with a large prostate volume or more severe (storage) LUTS. Additionally, persistent PIS is associated with an increased risk of acute urinary retention and symptom worsening. Of medical therapies approved for LUTS/BPH, the current evidence for a reduction of persistent PIS is greatest for the hexanic extract of
Serenoa repens
(HESr). This treatment relieves LUTS to the same extent as α
1
-adrenoceptor antagonists and short-term 5α-reductase inhibitors. Limited evidence is available on the effect of other mainstream LUTS/BPH treatments on persistent PIS.
Conclusions
Persistent PIS plays a central role in both the development and progression of LUTS/BPH. In men with LUTS/BPH who have a high chance of harbouring persistent PIS, HESr will not only improve LUTS, but also reduce (underlying) inflammation. Well-designed clinical studies, with a good level of evidence, are required to better evaluate the impact of BPH/LUTS medical therapies on persistent PIS.
Telocytes are a recently described stromal cell type widely distributed in various organs including the female and male reproductive systems. This study was aimed to investigate for the first time ...the existence, distribution and characteristics of telocytes in normal human testis by an integrated morphological approach (immunohistochemistry, immunofluorescence and transmission electron microscopy). We found that telocytes displaying typical long and moniliform prolongations and coexpressing CD34 and PDGFRα formed networks in the outer layer of peritubular tissue and around Leydig cells and vessels in the intertubular stroma. Testicular telocytes were immunophenotypically negative for CD31, c-kit/CD117 as well as α-SMA, thus making them clearly distinguishable from myoid cells/myofibroblasts located in the inner layer of peritubular tissue. Transmission electron microscopy confirmed the presence of cells ultrastructurally identifiable as telocytes (i.e. cells with telopodes alternating podomers and podoms) in the aforementioned locations. Intercellular contacts between neighboring telocytes and telopodes were observed throughout the testicular stromal compartment. Telopodes intimately surrounded and often established close contacts with peritubular myoid cells/myofibroblasts, Leydig cells and vessels. Extracellular vesicles were also frequently detected near telopodes. In summary, we demonstrated that telocytes are a previously neglected stromal component of human testis with potential implications in tissue homeostasis deserving further investigation.
Abstract Context Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the ...treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE). Objective Update of the latest evidence on the mechanisms of action, evaluate the current meta-analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE. Evidence acquisition Literature analysis of basic researches on PDE5-Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5 mg. Evidence synthesis Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35–4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25–5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01–1.43). Pooled data analyses revealed that tadalafil 5 mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement. Conclusions PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking. Patient summary We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction.
Abstract Context This review focuses on the relationship among sexual dysfunction (SD), lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and related therapies. Objective ...We reviewed the current literature to provide an overview of current data regarding epidemiology and pathophysiology of SD and LUTS. Moreover, we analysed the impact of currently available therapies of LUTS/BPH on both erectile dysfunction (ED) and ejaculatory dysfunction and the effect of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with ED and LUTS. Evidence acquisition We conducted a Medline search to identify original articles, reviews, editorials, and international scientific congress abstracts by combining the following terms: benign prostatic hyperplasia, lower urinary tract symptoms, sexual dysfunction, erectile dysfunction, and ejaculatory dysfunction. Evidence synthesis We conducted a comprehensive analysis of more relevant general population–based and BPH/LUTS or SD clinic-based trials and evaluated the common pathophysiologic mechanisms related to both conditions. In a further step, the overall impact of current BPH/LUTS therapies on sexual life, including phytotherapies, novel drugs, and surgical procedures, was scrutinized. Finally, the usefulness of PDE5-Is in LUTS/BPH was critically analysed, including preclinical and clinical research data as well as possible mechanisms of action that may contribute to the efficacy of PDE5-Is with LUTS/BPH. Conclusions Community-based and clinical data demonstrate a strong and consistent association between LUTS and ED, suggesting that elderly men with LUTS should be evaluated for SD and vice versa. Pathophysiologic hypotheses regarding common basics of LUTS and SD as discussed in the literature are (1) alteration of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway, (2) enhancement of RhoA–Rho-kinase (ROCK) contractile signalling, (3) autonomic adrenergic hyperactivity, and (4) pelvic atherosclerosis. The most important sexual adverse effects of medical therapies are ejaculation disorders after the use of some α-blockers and sexual desire impairment, ED, and ejaculatory disorders after the use of α-reductase inhibitors. Minimally invasive, conventional, and innovative surgical treatments for BPH may induce both retrograde ejaculation and ED. PDE5-Is have demonstrated significant improvements in both LUTS and ED in men with BPH; combination therapy with PDE5-Is and α1-adrenergic blockers seems superior to PDE5-I monotherapy.
Abstract Context The correlation among metabolic syndrome, lower urinary tract symptoms (LUTS), and cardiovascular disease (CVD) is well established. In particular, CVD has been proposed as a ...potential risk factor for both LUTS progression and severity. Objective To evaluate whether LUTS severity can be considered as a significant risk factor of major adverse cardiac events (MACE) in the male population. Evidence acquisition A systematic literature search was performed using PubMed, Google Scholar, and Scopus. The combination of the following keywords was adopted in a free-text strategy: benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) and cardiovascular, cardio, major adverse cardiac events, MACE, heart disease, heart, myocardial infarction, myocardial, infarction, stroke, ischemic events, ischemic, cardiac death, coronary syndrome . We included all cross-sectional and longitudinal trials enrolling men and comparing the prevalence or incidence of MACE in men with moderate to severe LUTS compared with those without LUTS or with mild LUTS. The studies in which only nocturia was evaluated were excluded from the analysis. Evidence synthesis Of 477 retrieved articles, 5 trials longitudinally reported the incidence of MACE in patients with moderate to severe LUTS in comparisons to those with mild or no LUTS and 10 studies reported the prevalence of history of MACE at enrollment. All were included in the present meta-analysis. Among cross-sectional studies, 38 218 patients and 2527 MACE were included in the meta-analysis. The mean age of enrolled patients was 62.2 ± 8.0 yr. Presence of moderate to severe LUTS significantly increased the risk of reported history of MACE ( p < 0.001). Metaregression analyses showed that the risk of MACE was lower in older patients and higher in those with diabetes. The association between LUTS-related MACE and diabetes was confirmed in a multivariate regression model after adjusting for age (adjusted r = 0.498; p < 0.0001). Longitudinal trials included 25 494 patients and 2291 MACE. The mean age of enrolled patients was 52.5 ± 5.5 yr, and mean follow-up was 86.8 ± 22.1 mo. Presence of moderate to severe LUTS was associated with an increased incidence of MACE compared with the rest of the sample (odds ratio: 1.68; 95% confidence interval, 1.13–2.50; p = 0.01). Conclusions Men with moderate to severe LUTS seem to have an increased risk of MACE. A holistic approach in considering the morbidities of aging men should be strongly encouraged and represents an important role for the practicing urologist. Patient summary We evaluated whether the severity of lower urinary tract symptoms could be considered as a significant risk factor for major adverse cardiac events (MACE) in the male population. We demonstrated that men with moderate to severe LUTS have an increased risk of MACE.
Several drugs, currently used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), can be associated with bothersome sexual side effects, including ejaculatory ...dysfunction (EjD).
To provide a systematic review and meta‐analysis of the available randomized clinical trials (RCTs) reporting the impact of medical treatments for LUTS due to BPH on ejaculatory function.
EjD related to medical treatments for LUTS.
A systematic literature search was performed using PubMed, Scopus and Cochrane databases. EjD was identified using both free text (“ejaculat*,” “retrograde ejaculation,” “anejaculation,” “ejaculatory dysfunction”) and Mesh (“Ejaculation”) searches.
Of 101 retrieved articles, 23 were included in the present meta‐analysis. EjD was significantly more common with alpha‐blockers (ABs) than with placebo (OR:5.88; P < 0.0001), in particular, considering Tamsulosin (OR:8.58; P = 0.006) or Silodosin (OR:32.5; P < 0.0001), with Tamsulosin associated with significantly lower risk of EjD than Silodosin (OR:0.09; P < 0.00001). Conversely, Doxazosin and Terazosin were associated with a risk similar to placebo. Meta‐regression showed that EjD was associated with IPSS and with Qmax both before and after treatment with ABs, while multivariate analysis demonstrated that EjD was independently associated with the improvement of IPSS (adj.r:0.2012; P < 0.0001) and Qmax (adj.r:0.522; P < 0.0001).
EjD was significantly more common with 5ARIs as compared with placebo (OR:2.73; P < 0.0001). Both Finasteride (OR 2.70; P < 0.0001) and Dutasteride (OR 2.81; P = 0.0002) were associated with significantly higher risk of EjD than placebo. EjD was significantly more common with combination therapy as compared with ABs alone (OR:3.75; P < 0.0001),or with 5ARIs alone (OR:2.76; P = 0.02).
ABs and 5ARI were both associated with significantly higher risk of EjD than placebo. More the AB is effective over time, greater is the incidence of EjD. Finasteride has the same risk of Dutasteride to cause EjD. Combination therapy with ABs and 5ARIs resulted in a 3‐fold increased risk of EjD as compared with ABs or 5ARIs alone. These data can be relevant both for drug selection and patients counseling. Gacci M, Ficarra V, Sebastianelli A, Corona G, Serni S, Shariat SF, Maggi M, Zattoni F, Carini M, and Novara G. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: A systematic review and meta‐analysis. J Sex Med 2014;11:1554–1566.
Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in ...human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.
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