Biopsychosocial approach to male chronic pelvic pain syndrome: recent treatments and trials.

INTRODUCTION: Chronic pelvic pain syndrome (CPPS) is a common urologic condition that can cause significant disability in affected individuals. Physiologic explanations of chronic pain are often incomplete; appropriate management of CPPS includes recognition of biological, psychological, and social elements, known as the biopsychosocial model. OBJECTIVE: The aim of this narrative review is to investigate treatments for men with CPPS, with a special focus on those utilizing the biopsychosocial model of care. METHODS: A comprehensive literature search was conducted on the electronic databases PubMed, Embase, and Cochrane Library, using relevant Medical Subject Heading terms and keywords related to CPPS treatments. The search was limited to studies published in English from inception to January 2023. Additionally, reference lists of selected studies were manually reviewed to find studies not identified by the initial search. Studies were included if they investigated pharmacologic or nonpharmacologic treatments for men with CPPS. RESULTS: A total of 30 studies met the inclusion criteria. Antibiotics, α-blockers, nonsteroidal anti-inflammatory drugs, gabapentinoids, antidepressants, and phosphodiesterase type 5 inhibitors were among the pharmacologic agents included in trials attempting to reduce symptoms of male CPPS. Studies that focused on treating CPPS without medication included interventions such as shockwave therapy, acupuncture, physical therapy, botulinum toxin, cryotherapy, electrotherapy, exercise, and cognitive behavioral therapy. CONCLUSION: α-Blockers and nonsteroidal anti-inflammatory drugs have shown promising results in treating CPPS in men, while the effectiveness of antibiotics remains controversial. Antidepressants and phosphodiesterase type 5 inhibitors may also be useful in decreasing symptoms in patients with CPPS. Treatments such as pelvic floor muscle therapy, acupuncture, shockwave therapy, and cognitive behavioral therapy must be considered effective complements to medical management in men with CPPS. While these interventions demonstrate benefits as monotherapies, the individualization and combination of treatment modalities are likely to result in reduced pain and improved quality of life.

Efficacy and safety assessment of traditional Chinese medicine for erectile dysfunction: A meta-analysis and trial sequential analysis.

BACKGROUND: Several patients with erectile dysfunction do not accept or benefit from conventional therapy with phosphodiesterase type 5 inhibitors; thus, alternative and complementary therapies are in need. Traditional Chinese medicine has been treating erectile dysfunction in China, but its clinical value is inconclusive. OBJECTIVE: To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating erectile dysfunction. METHODS: Randomized controlled trials were retrieved from a comprehensive search in the literature published in the past decade from the Web of Science, PubMed, Embase, Cochrane Library, SinoMed, China National Knowledge Internet, WanFang, and VIP. We performed a meta-analysis of the International Index of Erectile Function 5 questionnaire scores, clinical recovery rates, and testosterone levels using Review Manager 5.4 software. The trial sequential analysis was conducted to check the results. RESULTS: A total of 45 trials with 5016 patients were included. Meta-analysis results showed that traditional Chinese medicine effectively improved the International Index of Erectile Function 5 questionnaire scores (weighted mean difference = 3.78, 95% confidence interval: 3.12, 4.44; p < 0.001), clinical recovery rates (risk ratio = 1.57, 95% confidence interval: 1.38, 1.79; p < 0.001), testosterone levels (weighted mean difference = 2.42, 95% confidence interval: 1.59, 3.25; p < 0.001) compared with the controls. The single and add-on applications of traditional Chinese medicine could improve the International Index of Erectile Function 5 questionnaire score (p < 0.001). The trial sequential analysis confirmed the robustness of the analysis of the International Index of Erectile Function 5 questionnaire scores. A significant difference in the incidence of adverse effects between the treatment and control groups was not observed (risk ratio = 0.82, 95% confidence interval: 0.65, 1.05; p = 0.12). CONCLUSION: Traditional Chinese medicine can gain better responses in improving the International Index of Erectile Function 5 questionnaire scores, clinical recovery rates, and testosterone levels as an alternative and complementary treatment, with no increase in side effects. However, more standardized, long-term, traditional Chinese medicine and integrative therapy clinical trials are needed to support the clinical application of traditional Chinese medicine.

An Electrophysiological Technique to Accurately Diagnose and Treat Erectile Dysfunction.

Erectile dysfunction (ED) is a common disease in males. In the past, the first-line treatment of ED was mainly noninvasive-psychotherapy and oral phosphodiesterase 5 (PDE5) inhibitors. Oral PDE5 inhibitors often need to be used before sexual intercourse and do not repair the pathological damage; hence, the therapeutic effect for secondary ED caused by neurological or endocrine disorders is poor. Second-line treatments mainly include penile corpus cavernosum injection of alprostadil, transurethral administration, vacuum negative pressure devices, and other methods, with obvious side effects such as local pain. The third-line treatment mainly refers to penile prosthesis implantation. Indications of this treatment are strict, complications such as mechanical failure and infection may occur after operation, and it is expensive. Other treatments such as stem cell therapy and gene therapy are still in the experimental research stage and have not been used in clinics. A new treatment based on an electrophysiological technique combines a medical infrared thermal imager with low-frequency (20-50 Hz) neuromuscular electrical stimulation, which has achieved good results in the prevention and treatment of female pelvic floor dysfunction. Male generative organs are located in the pelvic floor area, and their normal function not only depends on the integrity of the structure and function of the male generative organs, but is also closely related to the blood vessels, nerves, muscles, and other pelvic floor organs. Therefore, this electrophysiological technique was applied to male ED, focusing on the observation of the penis, groin, and hypogastrium for accurate diagnosis and treatment. This demonstrated effective improvement in the conscious erectile status and erectile function scores of patients suffering from ED.

Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: In Erectile dysfunction (ED) patients, phosphodiesterase type 5 (PDE5) inhibitors are considered as the first-line therapy. However, 30-50% of ED patients fail to follow this therapeutic option because of adverse events, lack of efficacy, or drug costs. Antioxidant supplementation is widely applied in clinical practice and viewed as a potential therapeutic option for ED. Therefore, it is attractive to assess the effect of antioxidants supplementation on ED patients. OBJECTIVES: To evaluate the effects of antioxidants supplementation on ED. METHODS: Published randomized controlled trials of antioxidants in ED were searched in the PubMed, Embase, and Cochrane Library databases from inception to October 3, 2021. Meta-analyses were carried out using a random-effects model. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: Eighteen studies with 1,331 ED patients were included in the study. Compared with placebo, antioxidants alone treatment showed a statistical increase in International Index of Erectile Function (IIEF) score (SMD = 1.93; 95% CI: 0.15, 3.72; P = .034). Compared with placebo, antioxidants compound treatment elicited a significant increase in IIEF score (SMD = 2.74; 95% CI: 1.67, 3.81; P < .001) as well as sexual satisfaction score (SMD = 1.61; 95% CI: 0.63, 2.59; P = .001). Compared with the PDE5 inhibitors alone, combination of PDE5 inhibitors and antioxidants showed a significant increase in IIEF score (SMD = 1.1; 95% CI: 0.51, 1.68; P < .001) and sexual satisfaction score (SMD = 1.28; 95% CI: 0.06, 2.51; P = .04). CONCLUSION: This study found that the effect of antioxidant alone treatment on ED may be limited. However, antioxidant compound treatment, as well as combination of PDE5 inhibitors and antioxidants, were associated with improved ED, and can be considered as an accessary therapeutic option for ED. Su L, Yang Z, Qu H, et al. Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sex Med Rev 2022;10:754-763.

An up-to-date overview of the pharmacotherapeutic options for premature ejaculation.

INTRODUCTION: Premature ejaculation (PE) is a sexual dysfunction of unknown etiology affecting a substantial number of males and deteriorating sexual health and quality of life of the patient and his partner. Treatment still remains challenging; however, pharmacotherapy is considered the mainstay of therapy with behavioral and psychosexual interventions being particularly important as adjudicate procedures, within the context of a holistic approach. AREAS COVERED: The authors review the literature on the available medications for PE, both officially registered and non-registered. Currently, only dapoxetine and an anesthetic spray containing lidocaine and prilocaine (Fortacin™) are officially approved, with the rest being used off-label. Herein, updated data regarding the efficacy and safety of the pharmaceutical agents are presented. EXPERT OPINION: On-demand dapoxetine is reportedly efficacious and safe in treating lifelong PE and is the first medication to be approved for this purpose. Fortacin has also shown considerable efficacy and may be reliably used on-demand. Phosphodiesterase type 5 inhibitors (PDE5Is) have been found to be effective in the treatment of PE and are therefore recommended either as monotherapy or combined with other therapies (i.e. dapoxetine). Adverse events of any therapy should be taken under consideration. Physicians should encourage patients to discuss their needs and expectations and grade any improvement of their condition with treatment.

Mirabegron improves erectile function in men with overactive bladder and erectile dysfunction: a 12-week pilot study.

Phosphodiesterase type 5 inhibitors (PDE5i) is the only approved oral treatment for erectile dysfunction (ED) in the US, and alternative management remains necessary when this treatment fails or is contraindicated. Targeting other pathways than the NO-cGMP pathway and/or combining this approach with PDE5i may introduce new treatments for men who are unresponsive to PDE5i. This study aims to evaluate whether Mirabegron improves erectile function in men with concurrent overactive bladder and mild to moderate ED. Twenty subjects, 40-70 years old, registering International Index of Erectile Function (IIEF) score 11-25 and International Prostate Symptom Score 8-20, were treated with Mirabegron therapy for 12 weeks. Study participants were re-administered IIEF and OAB-q questionnaires on weeks 2, 4, 8, and 12 and assessed for adverse events. The primary and secondary endpoints were an increase in the IIEF-5 score of 4 units and a decrease in the Overactive Bladder questionnaire (OAB-q) symptom severity score of 10 units between study time points. Thirteen men completed the 12-week study. Mirabegron treatment improved the IIEF-5 scores in five patients (38.4%) by 4 points or more, whereas IIEF-5 scores were not affected by Mirabegron treatment in eight patients (61.5%). There were no clinically relevant decreases in the IIEF-5 score. Significant improvements were observed in intercourse satisfaction at week eight compared to baseline (p = 0.01). Orgasmic function and sexual desire were not affected by Mirabegron treatment. As expected, Mirabegron treatment reduced OAB symptoms based on OAB-q short form (p = 0.006) and OAB-q total health-related quality of life (HRQL) scores compared to baseline (p = 0.03). Residual bladder volumes were not affected by treatment. No serious side effects were reported during the study period. This study suggests that Mirabegron may improve both EF and OAB-related symptoms in some individuals without causing serious adverse events.

Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: In Erectile dysfunction (ED) patients, phosphodiesterase type 5 (PDE5) inhibitors are considered as the first-line therapy. However, 30-50% of ED patients fail to follow this therapeutic option because of adverse events, lack of efficacy, or drug costs. Antioxidant supplementation is widely applied in clinical practice and viewed as a potential therapeutic option for ED. Therefore, it is attractive to assess the effect of antioxidants supplementation on ED patients. OBJECTIVES: To evaluate the effects of antioxidants supplementation on ED. METHODS: Published randomized controlled trials of antioxidants in ED were searched in the PubMed, Embase, and Cochrane Library databases from inception to October 3, 2021. Meta-analyses were carried out using a random-effects model. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: Eighteen studies with 1,331 ED patients were included in the study. Compared with placebo, antioxidants alone treatment showed a statistical increase in International Index of Erectile Function (IIEF) score (SMD = 1.93; 95% CI: 0.15, 3.72; P = .034). Compared with placebo, antioxidants compound treatment elicited a significant increase in IIEF score (SMD = 2.74; 95% CI: 1.67, 3.81; P < .001) as well as sexual satisfaction score (SMD = 1.61; 95% CI: 0.63, 2.59; P = .001). Compared with the PDE5 inhibitors alone, combination of PDE5 inhibitors and antioxidants showed a significant increase in IIEF score (SMD = 1.1; 95% CI: 0.51, 1.68; P < .001) and sexual satisfaction score (SMD = 1.28; 95% CI: 0.06, 2.51; P = .04). CONCLUSION: This study found that the effect of antioxidant alone treatment on ED may be limited. However, antioxidant compound treatment, as well as combination of PDE5 inhibitors and antioxidants, were associated with improved ED, and can be considered as an accessary therapeutic option for ED.

Structural Determination, Biological Function, and Molecular Modelling Studies of Sulfoaildenafil Adulterated in Herbal Dietary Supplement.

Unapproved ingredients included in herbal medicines and dietary supplements have been detected as adulterated synthetic drugs used for erectile dysfunction. Extraction from a dietary supplement was performed to isolate the compounds by HPLC analysis. The structural characterization was confirmed using mass spectrometry (ESI-TOF/MS and LC-MS/MS), 1H NMR, and 13C NMR spectroscopy techniques. Results identified the thus-obtained compound to be sulfoaildenafil, a thioketone analogue of sildenafil. The biological activities of this active compound have been focused for the first time by the experimental point of view performance in vitro. The results revealed that sulfoaildenafil can affect the therapeutic level of nitric oxide through the upregulation of nitric oxide synthase and phosphodiesterase type 5 (PDE5) gene expressions. This bulk material, which displays structural similarity to sildenafil, was analyzed for the presence of a PDE5 inhibitor using a theoretical calculation. These unique features of the potential activity of PDE5 protein and its inhibitors, sildenafil and sulfoaildenafil, may play a key consideration for understanding the mode of actions and predicting the biological activities of PDE5 inhibitors.

Natural phosphodiesterase 5 (PDE5) inhibitors: a computational approach.

In 1998, sildenafil was marketed as the first FDA-approved oral drug for the treatment of erectile dysfunction (ED). During the last two decades, the commercialization of other synthetic phosphodiesterase 5 (PDE5) inhibitors has been paralleled by the rise of remedies based on natural molecules from different chemical classes (flavonoids, polyphenols and alkaloids in general). In this work, a set of in silico tools were applied to study a panel of 30 natural compounds claimed to be effective against ED in the scientific literature or in folk medicine. First, pharmacokinetic properties were analysed to exclude the compounds lacking in specific drug-like features. Estimated binding energy for PDE5 and selectivity towards other PDE isoforms were then considered to highlight some promising molecules. Finally, a detailed structural investigation of the interaction pattern with PDE in comparison with sildenafil was conducted for the best performing compound of the set.

Medicinal plants as a potential source of Phosphodiesterase-5 inhibitors: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence and distress caused by erectile dysfunction (ED) to both male and female partners are increasing at a steady rate. ED has now become the most treated sexual disorder for men among young and old age groups due to varying physical and psychological factors. The treatment with synthetic Phosphodiesterase-5 (PDE5) inhibitors are cost-effective but due to adverse effects such as priapism, loss of vision, heart attack and syncope, the daily life patterns of these patients are distressed and hence the need for alternative medicaments or sources are of utmost important. Therefore, the exploration of medicinal plants as PDE5 inhibitors will be worthwhile in tackling the problems as many plant extracts and fractions have been long used as aphrodisiacs and sexual stimulants which may be found to be active against PDE5 enzyme. AIM OF THE STUDY: To provide a review on the different medicinal herbs traditionally used as natural aphrodisiacs, libido or sexual enhancers which are proven for their PDE5 inhibitory effect. MATERIALS AND METHODS: Ethnobotanical and scientific information was procured, reviewed and compiled from the literature search of electronic databases and search engines. RESULTS: A total of 97 medicinal plants exhibiting PDE5 inhibitory effect are reviewed in this paper which is supported by preclinical experimental evidence. Among them, 77 plants have been selected according to their traditional and ethnobotanical uses as aphrodisiacs and the rest are screened according to their effectiveness against predisposing factors responsible for ED and sexual dysfunction such as diabetes and hypertension or due to the presence of phytochemicals having structural similarity towards the identified natural PDE5 inhibitors. In addition, sixteen alkaloids, sixty-one phenolics and eight polycyclic aromatic hydrocarbons have been isolated or identified from active extracts or fractions that are exhibiting PDE5 inhibitory activity. Among them, isoflavones and biflavones are the major active constituents responsible for action, where the presence of prenyl group for isoflavones; and the methoxy group at C-5 position of flavones are considered essential for the inhibitory effect. However, the prenylated flavonol glycoside, Icariin and Icariside II isolated from Epimedium brevicornum Maxim (hory goat weed) are the most effective inhibitor, till date from natural sources. Traditional medicines or formulations containing extracts of Ginkgo biloba L., Kaempferia parviflora Wall. ex Baker, Clerodendrum colebrookianum Walp., Eurycoma longifolia Jack and Vitis vinifera L. are also found to be inhibitors of PDE5 enzyme. CONCLUSION: The review suggests and supports the rational use of traditional medicines that can be further studied for the development of potential PDE5 inhibitors. Many traditional medicines are still used in various regions of Africa, Asia and South America that are poorly characterized and experimented. Despite the availability of a vast majority of traditional formulations as aphrodisiacs or sexual stimulants, there exists a need for systemic evaluation on the efficacy as well as the mechanism of action of the herbal constituents for the identification of novel chemical moieties that can be further developed for maximum efficacy.

Soluble guanylyl cyclase stimulation and phosphodiesterase-5 inhibition improve portal hypertension and reduce liver fibrosis in bile duct-ligated rats.

BACKGROUND: In cirrhosis, the nitric oxide-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired, which contributes to increased intrahepatic vascular resistance (IHVR) and fibrogenesis. We investigated if sGC stimulation (riociguat (RIO)), sGC activation (cinaciguat (CINA)) or phosphodiesterase (PDE)-5 inhibition (tadalafil (TADA)) improves portal hypertension (PHT) and liver fibrosis. METHODS: Fifty male Sprague-Dawley rats underwent bile-duct ligation (BDL) or sham operation. RIO (0.5 mg/kg), CINA (1 mg/kg), TADA (1.5 mg/kg) or vehicle (VEH) was administered from weeks 2 to 4 after BDL. At week 4, invasive haemodynamic measurements were performed, and liver fibrosis was assessed by histology (chromotrope-aniline blue (CAB), Picro-Sirius red (PSR)) and hepatic hydroxyproline content. RESULTS: Cirrhotic bile duct-ligated rats presented with PHT (13.1 ± 1.0 mmHg) and increased IHVR (4.9 ± 0.5 mmHg⋅min/mL). Both RIO (10.0 ± 0.7 mmHg, p = 0.021) and TADA (10.3 ± 0.9 mmHg, p = 0.050) decreased portal pressure by reducing IHVR (RIO: -41%, p = 0.005; TADA: -21%, p = 0.199) while not impacting heart rate, mean arterial pressure and portosystemic shunting. Hepatic cGMP levels increased upon RIO (+239%, p = 0.006) and TADA (+32%, p = 0.073) therapy. In contrast, CINA dosed at 1 mg/kg caused weight loss, arterial hypotension and hyperlactataemia in bile duct-ligated rats. Liver fibrosis area was significantly decreased by RIO (CAB: -48%, p = 0.011; PSR: -27%, p = 0.121) and TADA (CAB: -21%, p = 0.342; PSR: -52%, p = 0.013) compared to VEH-treated bile duct-ligated rats. Hepatic hydroxyproline content was reduced by RIO (from 503 ± 20 to 350 ± 30 µg/g, p = 0.003) and TADA (282 ± 50 µg/g, p = 0.003), in line with a reduction of the hepatic stellate cell activation markers smooth-muscle actin and phosphorylated moesin. Liver transaminases decreased under RIO (AST: -36%; ALT: -32%) and TADA (AST: -24%; ALT: -27%) treatment. Hepatic interleukin 6 gene expression was reduced in the RIO group (-56%, p = 0.053). CONCLUSION: In a rodent model of biliary cirrhosis, the sGC stimulator RIO and the PDE-5 inhibitor TADA improved PHT. The decrease of sinusoidal vascular resistance was paralleled by a reduction in liver fibrosis and hepatic inflammation, while systemic haemodynamics were not affected.

Effect and mechanism of prophylactic use of tadalafil during pregnancy on l-NAME-induced preeclampsia-like rats.

INTRODUCTION: Preeclampsia (PE) is a serious maternal inflammatory disease with endothelial cell dysfunction, and there is a lack of effective treatment and prevention. Tadalafil is considered to be a promising drug for PE. This study aimed to determine whether and how tadalafil use during early pregnancy alleviates PE induced by N-nitro-l-arginine-methyl-ester (l-NAME), an antagonist of nitric oxide synthase, in rats. METHODS: Twenty-eight Sprague-Dawley (SD) rats were randomly divided into 4 equal groups on gestational day 0 (GD0): a pregnant control group, an l-NAME-treated PE group and two prophylactic low-dose and high-dose tadalafil groups. Blood pressure was measured on GD0, 5, 10, 15 and 20. Proteinuria was assessed on GD0 and 18. Femoral artery ultrasound was performed on GD19. Tissue sampling was performed on GD20. The perinatal outcomes, placenta and kidney tissue morphology, and endothelial and inflammatory markers were examined. RESULTS: Prophylactic administration of low and high doses of tadalafil improved l-NAME induced hypertension, proteinuria, maternal weight loss during pregnancy, fetal growth restriction and flow-mediated dilatation, balanced endothelial-relative factors, and alleviated inflammation activation in placenta and kidney tissue. What's more, in some results, the HT group performed better than the LT group. DISCUSSION: Our results indicate that prophylactic use of tadalafil in l-NAME-induced PE-like rat models alleviates PE symptoms, promotes fetal growth, protects endothelial function and reduces inflammation, suggesting that tadalafil may be a potential drug for the prevention of PE.

Chinese herbal medicine combined with tadalafil for erectile dysfunction: a systematic review and meta-analysis.

BACKGROUND: Erectile dysfunction (ED) is a tough problem in medicine. This article aims to provide the latest evidence for the efficacy and safety of traditional Chinese medicine (TCM) combined with tadalafil in treatment of erectile dysfunction. METHODS: All randomized controlled trials that Chinese herbal medicine combined with tadalafil for erectile dysfunction were included in databases of China National Knowledge Infrastructure (CNKI), Wanfang, Weip Database, China Biology Medicine disc (CBM), MEDLINE, EMBASE, and Cochrane Library. The quality of the included articles was evaluated using Cochrane Reviewer's Handbook 5.3, and meta-analysis was performed using Stata 13.1. RESULTS: A total of 11 studies including 451 cases in the treatment group and 452 cases in the control group were obtained. Compared with tadalafil alone, meta-analysis suggests there were statistically significant differences in International Index of Erectile Function-5 (IIEF-5), effective rate, Sexual Encounter Profile questions 2 and 3 (SEP-Q2, SEP-Q3) between traditional Chinese medicine combined with tadalafil, and no statistically significant differences in side effects between the two groups. All included studies were tested for publication bias, and the results indicated that there was no significant bias. Two of the articles mentioned the scheme that traditional Chinese medicine combined with low-dose tadalafil for erectile dysfunction by down stairs. CONCLUSION: Traditional Chinese medicine combined with tadalafil has significant efficacy in the treatment of ED with no increase in side effects. The specific implementing regulations and effect of de-escalation therapy still need more long-term, multicenter, randomized, and double-blind clinical trials.

Early administration of phosphodiesterase 5 inhibitors after induction of diabetes in a rat model may prevent erectile dysfunction.

BACKGROUND: The possible role of phosphodiesterase 5 inhibitors (PDE5Is) in prevention of negative effect of diabetes mellitus (DM) on erectile function is not well settled. OBJECTIVES: To investigate the effect of early administration of vardenafil on erectile function, cavernosal structure, and genes expression in a rat model of DM. MATERIALS AND METHODS: This experimental study was carried out at Suez Canal University's research laboratory. This study was conducted on a total of 60 adult male Albino Wistar rats, aged 60-80 days and weighing an average of 200 g. Rats were equally divided into six groups of 10 rats each: Group I (sham); Group II (DM with no treatment); Groups III, IV, V, and VI received vardenafil started at day 1, week 4, week 8, and week 12 after induction of DM, respectively. Functional study assessment of all groups was performed before euthanization, and then tissues were harvested for histopathological, ultrastructural, and molecular examinations. RESULTS: There was a significant difference of intracavernosal pressure between early (94 ± 2.18) and late (40.5 ± 1.94) treatment groups (p = 0.011). Histopathological and ultrastructural changes of DM with no treatment and late treatment groups showed distorted cavernous architecture and extensive fibrosis. There was significant difference of smooth muscle to collagen ratio between early and late treatment groups (p = 0.035). There was significant upregulation of nNOS(p = 0.021) and iNOS (p = 0.047) in early vs. late treatment group. The difference was insignificant in eNOS (p = 0.386) or TGF-ß1(p = 0.149). DISCUSSION AND CONCLUSION: Early treated rats with vardenafil had preserved erection and normal cavernosal structure, ultrastructure and gene expression of iNOS, nNOS, eNOS, and TGF-ß1. Quantification of gene expression would improve our knowledge regarding cytokines expression and molecular background of DM-associated ED. Clinical application of this result may encourage early administration of PDE5I to prevent deleterious effects of DM on erectile function in newly diagnosed DM patients with probable uncontrolled blood glucose.

Brazilian guidelines for the pharmacological treatment of idiopathic pulmonary fibrosis. Official document of the Brazilian Thoracic Association based on the GRADE methodology

Idiopathic pulmonary fibrosis (IPF) is a form of chronic interstitial lung disease of unknown cause, which predominantly affects elderly men who are current or former smokers. Even though it is an uncommon disease, it is of great importance because of its severity and poor prognosis. In recent decades, several pharmacological treatment modalities have been investigated for the treatment of this disease, and the classic concepts have therefore been revised. The purpose of these guidelines was to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of IPF in Brazil. We sought to provide guidance on the practical issues faced by clinicians in their daily lives. Patients of interest, Intervention to be studied, Comparison of intervention and Outcome of interest (PICO)-style questions were formulated to address aspects related to the use of corticosteroids, N-acetylcysteine, gastroesophageal reflux medications, endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, pirfenidone, and nintedanib. To formulate the PICO questions, a group of Brazilian specialists working in the area was assembled and an extensive review of the literature on the subject was carried out. Previously published systematic reviews with meta-analyses were analyzed for the strength of the compiled evidence, and, on that basis, recommendations were developed by employing the Grading of Recommendations Assessment, Development and Evaluation approach. The authors believe that the present document represents an important advance to be incorporated in the approach to patients with IPF, aiming mainly to improve its management, and can become an auxiliary tool for defining public policies related to IPF.

[Efficiency of phosphodiesterase-5 inhibitors for treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia and concomitant erectile dysfunction].

Lower urinary tract symptoms (LUTS) in combination with benign prostatic hyperplasia and erectile dysfunction are more common than commonly thought. Unfortunately, urologists often dont ask about concomitant erectile dysfunction in patients with irritative or obstructive symptoms, which leads to the progression of underline disease, a deterioration in the quality of sexual life, and, as a result, overall quality of life. The relevant studies of recent years dedicated to feasibility of using tadalafil 5 mg a day are analyzed in the article. In addition, the results of scientific work conducted on the Department of Urology and Andrology of Faculty of Fundamental Medicine of Lomonosov Moscow State University, whose aim was to study the efficiency of phosphodiesterase-5 inhibitors in patients with LUTS of varying severity in combination with other types of drugs, are presented. Tadalafil in a dose 5 mg leads to a decrease in the severity of LUTS, as confirmed by a decrease in the mean I-PSS score by 2.19 points in the presented studies. No significant changes were found in Qmax (>0,05). We also proved in our work that phosphodiesterase-5 inhibitor can supplement any combined therapy for benign prostatic hyperplasia in the case of concomitant erectile dysfunction. Tadalafil in a dose 5 mg once a day can be recommended as monotherapy for patients with moderate LUTS caused by benign prostatic hyperplasia with concurrent erectile dysfunction, as an alternative to conventional treatment schemes.

An Evaluation of a Clinical Care Pathway for the Management of Men With Nonorganic Erectile Dysfunction.

INTRODUCTION: There exists little literature on the outcomes of the medical management of men with erectile dysfunction (ED) with no overt organic etiology. AIM: This study was conducted to assess the outcomes of men with nonorganic ED treated medically. METHODS: All patients had normal hormone profiles and vascular assessment. All were given a trial of a phosphodiesterase type 5 inhibitor (PDE5i). If no improvement was experienced, intracavernosal injection (ICI) therapy was administered. All patients were encouraged to seek a consultation with a mental health professional. MAIN OUTCOME MEASURE: Patient demographics, medical comorbidities, hormone and hemodynamics assessments, and change in International Index of Erectile Function scores of patients were recorded. RESULTS: 116 men with a mean age or 38 ± 19 (range 16-57) years were studied. 21% had mild ED, 47% had moderate ED, and 32% had severe ED. 21% had seen a psychiatrist. 81% of patients responded to PDE5i with a penetration hardness erection on follow-up (mean duration of 7 ± 3 months postcommencement of PDE5i). However, only 68% of these were capable of a consistently good response. The mean Erectile Function domain score on PDE5i for the entire group improved from 18 ± 11 to 22 ± 6 (P = .01), and for PDE5i responders it was 27 ± 4 (P < .001). 28% of men (22 PDE5i failures and 10 with a mixed response to PDE5i) attempted ICI, all obtaining consistently functional erections. At a mean time point of 11 ± 5 months, 83% of those responding to PDE5i had ceased using PDE5i due to a lack of need. 11% of those using ICI continued to use them 6 months after starting ICI; the remainder had been transitioned back to PDE5i. Of the 29 patients in the latter subgroup, 66% were no longer using PDE5i consistently due to a lack of need. CLINICAL IMPLICATIONS: Not all men with nonorganic ED respond to PDE5i initially and many of those who respond do so only intermittently; such patients are potentially curable, using erectogenic pharmacotherapy for erectile confidence restoration, most men are capable of being weaned from drug therapy. STRENGTHS & LIMITATIONS: The strengths of the study are the large number of patients and the use of serial validated instruments to assess erectile function outcomes. As a weakness, despite normal hormone and vascular assessments, the diagnosis of nonorganic ED is still a presumptive one. CONCLUSION: Medical management of nonorganic ED utilizing the process of care model results in cure in a large proportion of such patients. The transient use of ICI in some patients permits successful PDE5i rechallenge. Jenkins LC, Hall M, Deveci S, et al. An Evaluation of a Clinical Care Pathway for the Management of Men With Nonorganic Erectile Dysfunction. J Sex Med 2019;16:1541-1546.

Ocimum gratissimum Linn. Leaves reduce the key enzymes activities relevant to erectile dysfunction in isolated penile and testicular tissues of rats.

BACKGROUND: Ocimum gratissimum L. is a medicinal plant widely grown in tropical and subtropical regions with the leaf decoction usually taken in folk medicine to enhance erectile performance in men although the probable mechanism of actions remains undetermined. This study examined the inhibitory potentials of Ocimum gratissimum leaves on some key enzymes associated with erectile dysfunction in penile and testicular tissues of the rat. METHODS: Inhibitory effect of aqueous extract (1:10 w/v) of O. gratissimum leaves on the activities of phosphodiesterase-5 (PDE-5), arginase, angiotensin I -converting enzyme (ACE), and acetylcholinesterase (AChE) in penile and testicular tissues were assessed. Also, the extract was investigated for ferric reducing antioxidant property(FRAP) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical scavenging abilities. RESULTS: The extract showed higher PDE-5 (IC50 = 43.19 µg/mL), ACE (IC50 = 44.23 µg/mL), AChE (IC50 = 55.51 µg/mL) and arginase (IC50 = 46.12 µg/mL) inhibitory activity in the penile tissue than PDE-5 (IC50 = 44.67 µg/mL), ACE (IC50 = 53.99 µg/mL), AChE (IC50 = 60.03 µg/mL) and arginase (IC50 = 49.12 µg/mL) inhibitory activity in the testicular tissue homogenate. Furthermore, the extract scavenged free radicals and in a dose-dependent manner. CONCLUSION: The enzyme activities displayed might be associated with the bioactive compounds present in the extract which could possibly explain its use in the management of erectile dysfunction (ED).