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Introduction: Sildenafil citrate is an effective treatment for erectile dysfunction (ED). Despite established safety profile, its long-term ocular implications remain unclear. We evaluate the relationship between the duration of use with retinal nerve fibre layer (RNFL), macular and choroidal thickness. Materials and methods: A cross-sectional study was done between July 2020 and June 2021, among 47 ED patients on sildenafil. The subjects fulfilling the inclusion criteria underwent optical coherent tomography (OCT) to evaluate RNFL, macular and choroidal thickness. Linear regression analysis was done to assess the relationship between duration of use with OCT parameters. Other possible associated factors were evaluated. Results: Forty-seven patients with the mean age of 54.30±8.41 years old recruited. These patients had not experienced visual disturbance on each sildenafil use. There were significant correlations between diabetes mellitus (DM) (r=0.330, P=0.023), erection hardness score (EHS) (r=-0.469, P=0.001) and total cumulative dose (r=0.806, P=<0.001) with duration of use. Duration of use had significant negative linear relationship with the average RFNL (b = -0.284, P=<0.001), superior RNFL (b = -0.195, P=0.018), and inferior RNFL (b = -0.887, P=<0.001). Multiple linear regression (MLR) reveals average RNFL was also influenced by total cumulative dose (b = -0.003, P = 0.029). No significant relationship observed to the macular thickness. Significant linear relationship observed between duration of use with sub-foveal choroidal thickness (b = 0.640, P<0.001). Conclusion: Sildenafil in general does not cause visual symptoms, however subclinical ocular changes; RNFL thinning and choroidal thickening may be influenced by its duration of use. Long term ocular monitoring is recommended. [ABSTRACT FROM AUTHOR]

Sexual behaviors play a role in the social construction of masculinity. Moreover, this stereotype has been capitalized upon by pharmaceutical companies, as well as those that sell products not approved by the U.S. Food and Drug Administration, for purposes of marketing sexual medicines. Stereotypical notions of masculinity, however, also emphasize the importance of self-reliance, which may cause some to look unfavorably upon the use of sexual medicine. Consistent with this notion, a male target was viewed as more masculine when his female partner consistently reached orgasm, unless he had no history of erectile dysfunction (ED), but was taking Viagra anyway (Experiment 1; N = 522). In addition, when his partner consistently reached orgasm, ratings of his sexual esteem were also lower if he used Viagra than if he did not, but only if he had no history of ED. In Experiment 2 (N = 711), although there was no effect of a male target's use of testosterone, social perception of his masculinity and sexual esteem increased as his "natural" levels of testosterone increased. In addition, exploratory analysis revealed that if the male target had low (but not normal or high) "natural" levels of testosterone, ratings of his masculinity were higher if his female partner consistently had an orgasm, which suggests that female orgasm served to "rescue" masculinity. Because expectations about drugs drive their use, it is important to address preconceived notions about the use of sexual medicines for purposes of enhancing masculinity and sexual esteem, as the social perception of their use is much more complex. [ABSTRACT FROM AUTHOR]

Purpose: A national additional risk minimization measures (aRMMs) program was implemented to train pharmacists for safe supply of non-prescription Viagra Connect® (VC) to erectile dysfunction (ED) patients in United Kingdom (UK). A survey aimed to evaluate the effectiveness of aRMMs. Methods: A cross-sectional, web-based survey enrolled ED patients who purchased at least 1 supply of VC in UK, using a structured self-administered questionnaire. Patients were assessed for the suitability of VC and received appropriate advice from pharmacists. Descriptive statistics were used. Results: The final sample had 297 patients, who reported that pharmacists inquired about blood pressure and heart comorbidities (91.9%), relevant illnesses (87.9%), medications (86.5%), ED diagnosis (82.2%), and were advised to consult their doctor regarding ED (51.2%). Furthermore, 85.5% of patients were advised on how to take VC correctly, 82.2% on possible side effects for which they might have to discontinue taking VC and consult their doctor, 80.1% on being informed that ED could be caused by underlying conditions. About 65.0% reported that they had visited (19.2%) or planned to visit (45.8%) their doctor. A majority (68.7%) also indicated that they had received advice on lifestyle modifications to manage their ED-related health risks. Conclusion: This survey provided a reasonable confirmation of the effectiveness of the VC aRMMs program and assurance that ED patients, when requesting and purchasing VC in UK pharmacies, are assessed appropriately for suitability of VC and receive the appropriate advice from pharmacists. Plain Language Summary: A national additional risk minimization measures (aRMMs) program was implemented to train pharmacists for safe supply of non-prescription VC to erectile dysfunction (ED) patients in United Kingdom (UK). A cross-sectional, web-based survey enrolled ED patients who purchased at least 1 supply of VC in UK, using a structured self-administered questionnaire. Patients were assessed for the suitability of VC and received appropriate advice from pharmacists. The final sample had 297 patients, who reported that pharmacists inquired about blood pressure and heart comorbidities, relevant illnesses, medications, ED diagnosis, and were advised to consult their doctor regarding ED. Additionally, most of the patients had consulted or planned to consult their doctors, on how to take VC correctly, on possible side effects for which they might have to discontinue taking VC and consult their doctor, on being informed that ED could be caused by underlying conditions, and on lifestyle modifications. A majority also indicated that they had received advice on lifestyle modifications to manage their ED-related health risks. This survey provided a reasonable confirmation of the effectiveness of the VC aRMMs program and assurance that ED patients, when requesting and purchasing VC in UK pharmacies, are assessed appropriately for suitability of VC and receive the appropriate advice from pharmacists. [ABSTRACT FROM AUTHOR]

Background: Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is widely used for the treatment of erectile dysfunction (ED). However, the safety profile of sildenafil, including adverse event (AEs), requires comprehensive evaluation. Methods: This retrospective pharmacovigilance study aimed to evaluate AEs linked to sildenafil by analyzing data sourced from the FDA Adverse Event Reporting System (FAERS) database. A case/non‐case design was utilized, and various algorithms including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) were employed to measure the signals indicating the presence of sildenafil‐related AEs. Results: Among 339,230 reports, 33,692 specifically mentioned sildenafil use. Most of AEs occurred in males over 60 years old. The United States accounted for the highest proportion of reported AEs. Severe outcomes, including death, disability, and life‐threatening events, were reported. Significant system organ class (SOC) included "Reproductive system and breast disorders" (SOC: 10038604), "Neoplasms benign, malignant and unspecified" (SOC: 10038738), "Vascular disorders" (SOC: 10047065), and "Blood and lymphatic system disorders" (SOC: 10005329). Noteworthy preferred terms (PTs) associated with sildenafil included "Vision blurred," "Flushing," "sudden hearing loss," "Painful erection," and "Priapism." Unexpected AEs, such as "Malignant melanoma," "Pulmonary hypertension," "Malignant melanoma in situ," "Pulmonary arterial hypertension," "Metastatic malignant melanoma," "Malignant melanoma stage III," "Malignant melanoma stage II," "Acquired hemophilia," "Aortic dissection rupture," and "Intracranial artery dissection" were also identified. Conclusions: These findings emphasize the importance of monitoring and understanding the potential risks associated with sildenafil. Further investigation is warranted to validate these associations and address previously unrecognized safety concerns. [ABSTRACT FROM AUTHOR]

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Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCβ2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition. [ABSTRACT FROM AUTHOR]

This research work studied the phenolic composition of Pentaclethra macrophylla (PM), the inclusion of dietary supplementation of PM leaves on sexual functions and its connection to inhibit enzymes (arginase and phosphodiesterase-5) and nitric oxide level, linked to type 2 diabetes-induced erectile dysfunction in rats. Gallic acid, chlorogenic and ellagic acids, Kaempferol, and epicatechin etc. was spotted with High performance liquid chromatography–diode array detector from PM extract. Twenty-five (25) rats were used for the study. Five rats were placed with basal diet; diets not supplemented with PM leaves (normal rat group) while twenty rats were made diabetic by feeding them with high fat diet for two weeks, prior to single injection with 35 mg/kg of streptozotocin (STZ). After checking with glucometer, experimental animals with blood glucose level >250 mg/dL were accepted as diabetic. The diabetic rats were subsequently divided into four groups of five rats each (n=5). The diabetic rats were placed on basal diet, or diets supplemented with PM leaves (10 % or 5 % inclusion) or sildenafil citrate (SC) The result revealed that PM supplemented diets caused significant (p<0.05) reduction in blood glucose level, and augmented erectile function by inhibiting arginase and PDE5 activities as well as enhancing nitric oxide level. In conclusion, dietary inclusion of PM leaves could serve as a potent nutraceutical source in hyperglycemia induced erectile dysfunction management. [ABSTRACT FROM AUTHOR]

Background: A lot of people come to us complaining about erectile dysfunction. These days, even those under the age of 30 frequently deal with the problem of early onset hypertension and diabetes. Material and Methods: The study comprised 70 consecutive patients who were referred from several departments, including general medical outpatient, psychiatry, diabetology, and urology. This study was conducted at the Department of Radiology, Sri Balaji Medical College. Renigunta, Tirupati, Andhra Pradesh, India between March 2023 to Jan 2024. Every patient complained of erectile dysfunction for at least half a year. A thorough clinical history and basic blood chemistry were performed on each subject. Results: These are a few instances of venous and arterial insufficiency patterns associated with erectile dysfunction. The individuals' ages ranged from 22 to 65 years old, with a mean age of 44. The average score of the 70 subjects on the SHIM questionnaire was 14.6. About 30% of the participants had no identified risk factors, despite the fact that diabetes and hypertension were the primary causes in the great majority of instances. Out of 70 participants, 56 responded normally to sildenafil and 59 to papaverine. Papaverine found that 21 individuals taking sildenafil had erectile dysfunction, compared to 18 who did not. Conclusion: Tab. Sildenafil significantly increases blood flow to the penile vasculature, according to the study, suggesting it may be useful as an erectogenic agent in penile Doppler studies when paired with self-tactile stimulation. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a serious condition characterized by bleeding within the brain tissue. Although the use of sildenafil, a vasodilator agent for erectile dysfunction, has been associated with rare cases of ICH, the combination of sildenafil usage and smoking as risk factors for ICH has not yet been reported. This case report describes the occurrence of ICH in a patient with a history of both sildenafil usage and heavy smoking.Case Presentation: A 53-year-old male, with a history of smoking and regular sildenafil use, was brought to the emergency department due to loss of consciousness with right-side weakness, he initially experienced with nausea, vomiting and dizziness after taking sildenafil 100mg tablet once. The Glasgow Coma Score (GCS) was 10 with side hemiparesis. Non-contrast CT revealed left thalamic acute hemorrhage with ventricular extension. Furthermore, a head CT angiography ruled out any vascular anomalies after that the patient was admitted to the intensive care unit (ICU) for conservative management. After three days on clinical and neurological improvement, the patient was transferred to the inpatient ward for further management, monitoring and physiotherapy. On day 6, the patient was discharged and planned for flow up.Conclusion: This rare case highlights the need for further research and awareness regarding the potential risks associated with the combination of sildenafil and heavy smoking. Healthcare professionals should carefully evaluate the individual risk factors of patients, educate them about potential complications, and consider alternative treatments if necessary. Additionally, patients should be encouraged to quit smoking and adopt a healthy lifestyle to minimize the risk of cerebrovascular events. [ABSTRACT FROM AUTHOR]

Phosphodiesterase type 5 (PDE5) is pivotal in cellular signalling, regulating cyclic guanosine monophosphate (cGMP) levels crucial for smooth muscle relaxation and vasodilation. By targeting cGMP for degradation, PDE5 inhibits sustained vasodilation. PDE5 operates in diverse anatomical regions, with its upregulation linked to various pathologies, including cancer and neurodegenerative diseases. Sildenafil, a selective PDE5 inhibitor, is prescribed for erectile dysfunction and pulmonary arterial hypertension. However, considering the extensive roles of PDE5, sildenafil might be useful in other pathologies. This review aims to comprehensively explore sildenafil's therapeutic potential across medicine, addressing a gap in the current literature. Recognising sildenafil's broader potential may unveil new treatment avenues, optimising existing approaches and broadening its clinical application. [ABSTRACT FROM AUTHOR]

Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association. A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis. Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma. [ABSTRACT FROM AUTHOR]

Background: Despite their efficacy and general safety, rare but devastating adverse drug reactions have been associated with phosphodiesterase type 5 inhibitors. Objectives: To determine the safety profile of oral phosphodiesterase type 5 inhibitors with a particular focus on priapism and malignant melanoma. Materials and methods: In this case–non‐case study, we queried the individual case safety reports for phosphodiesterase type 5 inhibitors within the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021. We included all individual case safety reports for sildenafil, tadalafil, vardenafil, and avanafil in men. For comparison, we also extracted the safety data from the Food and Drug Administration trials for these drugs. We assessed the safety profile of phosphodiesterase type 5 inhibitors by disproportionality analysis by measuring reporting odds ratio for their most commonly reported adverse drug reactions, once for all phosphodiesterase type 5 inhibitor reports and once for reports of oral phosphodiesterase type 5 inhibitor use in adult men (≥18 years old) with sexual dysfunction. Results: A total of 94,713 individual case safety reports for phosphodiesterase type 5 inhibitors were extracted. A total of 31,827 individual case safety reports were identified relating to adult men taking oral sildenafil, tadalafil, vardenafil, or avanafil for sexual dysfunction. The most common adverse drug reactions included poor drug efficacy (42.5%), headache (10.4% vs. 8.5%–27.6% [Food and Drug Administration]), abnormal vision (8.4% vs. ≤4.6% [Food and Drug Administration]), flushing (5.2% vs. 5.1%–16.5% [Food and Drug Administration]), and dyspepsia (4.2% vs. 3.4%–11.1% [Food and Drug Administration]). Priapism showed significant signals for sildenafil (reporting odds ratio = 13.81, 95% confidence interval: 11.75–16.24), tadalafil (reporting odds ratio = 14.54, 95% confidence interval: 11.56–18.06), and vardenafil (reporting odds ratio = 14.12, 95% confidence interval: 8.36–22.35). Comparing with other medications in VigiBase, sildenafil (reporting odds ratio = 8.73, 95% confidence interval: 7.63–9.99) and tadalafil (reporting odds ratio = 4.25, 95% confidence interval: 3.19–5.55) had significantly higher reporting odds ratios for malignant melanoma. Conclusion: Phosphodiesterase type 5 inhibitors show significant signals correlating with priapism among a large international cohort. Further clinical study is needed to elucidate whether this is from proper or inappropriate use or other confounding conditions, as analysis of pharmacovigilance data does not allow for quantifying the clinical risk. Also, there appears to be a relationship between phosphodiesterase type 5 inhibitor use and malignant melanoma, which warrants additional study to better understand causation. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs). Aim: This study aims to investigate and compare the characteristics of AEs associated with PDE5Is used for erectile dysfunction and identify any safety signals in a postmarketing surveillance database between 2010 and 2021. Methods: A descriptive analysis was conducted for all AEs reported to the Food and Drug Administration Adverse Event Reporting System for 4 PDE5Is—avanafil, sildenafil, tadalafil, and vardenafil—indicated for erectile dysfunction between January 2010 and December 2021. The frequency of the most reported AEs and outcomes were identified. A disproportionality analysis based on proportional reporting ratio (PRR) and reporting odds ratio (ROR) was conducted for the most common and clinically important AEs to identify signals to gain insights into potential differences in safety profiles. Outcomes: The outcome measures of the study are frequency of reported AEs and outcomes following AE. Results: A total of 29 236 AEs were reported for PDE5Is during the study period. The most reported AE was "drug ineffective" with 7115 reports (24.3%). Eight safety signals were detected across the 4 drugs. Key signals were sexual disorders (PRR, 3.13 [95% CI, 2.69-3.65]; ROR, 3.24 [95% CI, 2.77-3.79]) and death (PRR, 3.17 [2.5-4.01]; ROR, 3.211 [2.52-4.06]) for sildenafil, priapism (PRR, 3.63 [2.11-6.24]; ROR, 3.64 [2.12-6.26]) for tadalafil, and drug administration error (PRR, 2.54 [1.84-3.52]; ROR, 2.6 [1.86-3.63]) for vardenafil. The most reported outcomes were other serious events with 6685 events (67.2%) and hospitalization with 1939 events (19.5%). Clinical Implications: The commonly reported AEs and detected signals may guide clinicians in treatment decision making for men with erectile dysfunction. Strengths and Limitations: This is the first comprehensive report and disproportionality analysis on all types of AEs associated with PDE5Is used for erectile dysfunction in the United States. The findings should be interpreted cautiously due to limitations in the Adverse Event Reporting System, which includes self-reports, duplicate and incomplete reports, and biases in reporting and selection. Therefore, establishing a causal relationship between the reported AEs and the use of PDE5Is is uncertain, and the data may be confounded by other medications and indications. Conclusion: PDE5Is demonstrate significantly increased risks of reporting certain clinically important AEs. While these events are not common, it is imperative to continually monitor PDE5I use at the levels of primary care to national surveillance to ensure safe utilization. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound‐targeted MB destruction (UTMD)‐mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB‐cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO–cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to "awaken" the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation. [ABSTRACT FROM AUTHOR]

The Interventions Testing Program (ITP), funded by the National Institute on Aging (NIA), is a 22-year-old project that evaluates compounds to determine if they extend longevity in mice, with the hope that they will also have the same effect in humans. The ITP has tested over 60 drugs, dietary components, hormones, and other molecules, and has identified 12 compounds and two combinations that prolonged the lives of mice. The program is praised for its transparency, meticulous methods, commitment to replication, and publication of all results, even negative ones. While the ITP has not yet produced a treatment to slow human aging, it has identified molecules, such as the drug rapamycin, that have shown positive effects in counteracting some age-related conditions in people. However, turning these insights into treatments is challenging due to regulatory barriers and funding limitations. Nonetheless, the ITP continues to receive proposals for testing molecules and is seen as a valuable approach in the search for anti-aging interventions. [Extracted from the article]

Purpose: Ingestion of sildenafil citrate has performance-enhancing effects at high altitudes above 3800 m in able-bodied individuals. It is unknown whether it can improve the performance of athletes with spinal cord injury (SCI) at moderate altitudes (<2200 m), relevant to Paralympic competitions. As most men with SCI suffer from erectile dysfunction of neurologic origin and use sildenafil on a regular basis, it seems important to study the impact of sildenafil on exercise capacity. The outcome of this study is also relevant to the antidoping community. Methods: Twenty-seven healthy male wheelchair athletes with a motor-complete SCI participated in this prospective double-blind, randomized, placebo-controlled study. The participants performed arm cranking exercise to exhaustion at sea level and moderate altitude (2200 m) after ingestion of 50 mg sildenafil citrate or a placebo. Peak power output, peak oxygen uptake, peak heart rate, rating of perceived exertion, oxygen saturation, and lactate concentrations at exhaustion were measured. Results: Friedman analysis showed that peak power output at sea level was significantly higher (P =.004) under placebo treatment (median [minimum; maximum]: 120 W [35; 170]) compared with sildenafil (115 W [40; 165]). Blood oxygen saturation under sildenafil treatment at sea level (98% [81; 100]) was significantly higher (P =.006) compared with sildenafil treatment at moderate altitude (94% [85; 100]). All other parameters revealed no impact of sildenafil or altitude. Conclusions: In this study, the ingestion of sildenafil citrate in athletes with SCI demonstrated no positive effects on peak arm-cranking-exercise capacity compared with placebo either at sea level or at moderate altitude. [ABSTRACT FROM AUTHOR]

Background and Aims: Since the increasing prevalence of erectile dysfunction disease, the use of phosphodiesterase type 5 (PDE-5) inhibitors is widespread in the current era. The first and the most known molecule of PDE-5 inhibitors is sildenafil. It is widely used in the market. The second and more developed one is tadalafil. It is known that these substances are found in sexual stimulant food supplements as adulteration. In addition, food supplements can contain metals that can cause hazardous activity by accumulating. In our study, 11 randomly chosen sexual stimulant known products are studied which were bought from different stores in Edirne. Methods: Adulteration with sildenafil and tadalafil was determined by LC-MS/MS because of the enhanced accuracy and precision, general applicability, and higher selectivity. Also, the determination of 23 metals, including known heavy metals, was made with ICP-MS. Results: In the study, 7 of 11 samples detected at least 1 compound of sildenafil (up to 92.44 mg in one serving) or tadalafil (up to 23.62 mg in one serving). Neither of the samples exceeded the limits of metal daily intakes that are shown in Table 4. Conclusion: In past studies, adulteration was determined in food supplements, and it is still detected today. The results we obtained are engrossing for the regulations of sexual stimulant food supplement sales. Their additional effects on total daily intake raise health concerns. The data obtained from this study will contribute to inform consumers and health professionals about the status of food supplements in the market. [ABSTRACT FROM AUTHOR]

Background Inflammation is a key risk factor for heart disease and has also been linked to erectile dysfunction (ED). Sildenafil is a phosphodiesterase type 5 inhibitor with a strong antioxidant effect. Interleukin (IL)-18 is a proinflammatory factor. Excessive production and release of IL-18 disrupt the balance between IL-18 and IL-18 binding proteins in certain inflammatory diseases, leading to the occurrence of pathological inflammation. Aim We evaluated the effects of sildenafil on erectile function in a rat model of high-fat diet–induced ED. Methods Male Sprague Dawley rats (6 weeks old) were divided into 5 groups: control, ED, sildenafil, IL-18, and IL-18 + sildenafil. Subsequently, intracavernous pressure and mean arterial pressure were used to assess the erectile function of these rats. The expression of endothelial nitric oxide synthase, pyroptosis factors, and the ratio of smooth muscle cells and collagen fibers were evaluated in the serum and corpora tissue. Outcomes Exploring the role and mechanism of sildenafil in ED through NLRP3-mediated pyroptosis pathway. Results In comparison to the ED and IL-18 groups, there were statistically significant increases in the ratio of intracavernous pressure to mean arterial pressure, endothelial nitric oxide synthase expression, and the ratio of smooth muscle cells to collagen fibers following sildenafil intervention (P <.05). The sildenafil group and IL-18 + sildenafil group also showed statistically significant decreases the expression of NLRP3, caspase-1, and gasdermin D (P <.05). Clinical Implications Sildenafil can improve erectile dysfunction by inhibiting inflammation. Strengths and Limitations Strengths are that the relationship between pyroptosis and ED has been verified through in vitro and in vivo experiments. The limitation is that the conclusions drawn from animal and cells experiments need to be confirmed in clinical research. Conclusion Sildenafil may reduce the effect of IL-18–induced inflammation in high-fat diet–induced ED rats through NLRP3/caspase-1 pyroptosis pathway. [ABSTRACT FROM AUTHOR]

Oral phosphodiesterase inhibitors have emerged as a game changer for the treatment of erectile dysfunction (ED) since attaining FDA approval for its first member, sildenafil, in 1998. Topical penile therapy could be a viable replacement for oral medication that would transform the treatment of ED for many decades to come. This innovative idea could offer a safer topical alternative with less vision and cardiovascular side effects than the oral route. This work aims at developing proniosomal gels for three selected members (sildenafil, vardenafil, and tadalafil) and investigating the proniosomal gels on a rodent model. Niosomes derived from the parent proniosomal gels were characterized for entrapment efficiency (EE%), size, polydispersity index (PDI), zeta potential, and morphology. Proniosomal gels were evaluated for skin permeation, in vivo mating behaviors, and biochemical assays of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) post penile topical administrations. The optimized proniosomes loaded with tadalafil (F1-T) were compared with oral tablets (Cialis®). Proniosomal gels demonstrated significant enhancement of skin penetration by up to 5.5-fold, compared to control topical suspension. Tadalafil-loaded proniosomes showed superior skin permeability over sildenafil- and vardenafil-loaded proniosomes. In addition, significant improvement was noticed regarding intromission number, intromission ratio, NO, and cGMP for the proniosomal gel F1-T, compared to the untreated control. No statistically significant (p > 0.05) differences in sexual performance or biochemical parameters (NO and cGMP levels) were recorded among orally and topically (tadalafil proniosomal gel) administered groups. These findings support tadalafil topical penile therapy as a promising alternative to the oral route. [ABSTRACT FROM AUTHOR]

Background: In recent times, attention has been shifted from synthetic drugs to the use of medicinal plants and this has greatly improved reproductive functions. Abrusprecatorious plant has different parts which are used as diverse sources of naturally occurring chemicals that have a variety of therapeutic effects on the body. However, in this present study, we consolidated the reproductive property of Abrus precatorius in paroxetine-induced male reproductive dysfunction. Methods: Twenty four (24) male rats were divided into four (4) groups each containing six animals was used for this experiment following paroxetine-induced erectile dysfunction. Group one, received 1ml of distilled water, Group two received 20mg/kg of Paroxetine and 50mg/kg of sildenafil, Group three received 20mg/kg of Paroxetine and 300mg/kg of A. precatorius extract, Group four received 20mg/kg of Paroxetine and 900mg/kg of A. precatorius extract for 21 days. Results: Results from the studies reveal that there was significant decrease in the sperm motility of the rats administered with Abrus precatorius when compared with control. Interestingly, the high dose extract increased the serum testosterone levels significantly while the low dose extract significantly reduce the level of testosterone when compared with the control. Histological examination of the testes of treated rats displayed noticeable atrophy, which was characterized by disruption of the seminiferous epithelium and reduction in cell population of the Leydig cells. Conclusion: It appears that very high dose of Abrusprecatoriusmay induce infertility by increasing serum testosterone levels. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and adverse events of sildenafil monotherapy for benign prostatic hyperplasia (BPH) with its FDA-approved counterpart, tadalafil. Materials and Methods: In this single-arm self-controlled clinical trial, 33 patients were enrolled. All patients underwent a 6-week treatment with sildenafil, followed by a 4-week washout period and finally a 6-week treatment with tadalafil. Patients were examined on each appointment and post-void residual (PVR) urine, International Prostate Symptom Score (IPSS) and Quality of life index (IPSS-QoL index) were recorded subsequently. Efficacy of each drug regimen was then evaluated by comparing these outcome parameters. Results: Both sildenafil and tadalafil were shown to improve PVR (both p < .001), IPSS (both p < .001) and IP- SS-QoL index (both p < .001) significantly. Sildenafil was more effective than tadalafil in reducing PVR (mean difference (95%CI) = 9.91% (4.11, 15.72), p < .001) and ameliorating IPSS-QoL index (mean difference (95%CI) = 19.3% (4.47, 34.41), p = .027). Moreover, although not significant, sildenafil reduced IPSS more than tadalafil (mean difference (95%CI) = 3.33% (-0.22, 6.87), p = .065). Concurrent erectile dysfunction did not affect respon- siveness to therapy with either sildenafil or tadalafil but age was inversely related to post-treatment IPSS in both sildenafil (B = 0.21 (0.04, 0.37), p = .015) and tadalafil (B = 0.14 (0.02, 0.26), p = .021) regimens with a more prominent role in responsiveness to sildenafil (β = 0.31) compared to tadalafil (β = 0.19). Conclusion: Considering the significantly better improvement of PVR and IPSS-Qol index with sildenafil, this drug can be nominated as a suitable alternative for tadalafil as a BPH treatment, especially in younger patients who don’t have any contraindications. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to assess the comparative effectiveness of continuous positive airway pressure (CPAP) therapy and sildenafil pharmacological therapy in improving sexual function among patients with obstructive sleep apnea (OSA) and erectile dysfunction (ED). Materials and methods: Population: Patients affected by OSA and ED; Intervention: CPAP therapy vs. Comparison: Sildenafil pharmacological therapy; Outcomes: Improvement in erectile function, as measured by the International Index of Erectile Function 5 (IIEF-5) scoring system; Time: A systematic review of the literature from the past 20 years; Study Design: Observational studies comparing erectile function improvements after OSA treatment. Results: A total of eight papers were included in the qualitative summary, involving four hundred fifty-seven patients with ED and OSA. Erectile function improvements were observed in both treatment groups. After sildenafil and CPAP treatment, the mean IIEF-5 domain scores were 37.7 and 27.3, respectively (p < 0.001). Sildenafil 100 mg demonstrated a higher therapeutic impact compared to CPAP treatment. Conclusions: CPAP therapy significantly improved sexual parameters in most studies for OSA patients with ED. The findings suggest that CPAP therapy effectively alleviates erectile dysfunction symptoms, resulting in improved sexual performance in OSA patients. The comparison of the two treatments indicates that sildenafil has a more substantial therapeutic impact on erectile function than CPAP therapy; however, a combined treatment will provide a cumulative effect. [ABSTRACT FROM AUTHOR]

Objective: We conducted a questionnaire survey on the usability of sildenafil’s new form, sildenafil OD film. Material and Methods: We focused on 25 patients who desired erectile dysfunction treatment and ingested sildenafil OD films. The patients’ ages ranged from 21 to 79 years. Among them, 13 patients had taken tablets in the past and switched to OD film, and the other 12 patients strictly used only OD film. Survey questions covered (1) storage and portability, (2) storage place, (3) ease of administration, (4) proximity level with partner, (5) freeness from exposure to a partner or others, (6) opinions on administering OD film, (7) comparison with tablets, and (8) efficacy and side effects. Results: Among the patients who changed formulation types, 61.5% answered that OD film improved storage and portability compared to tablets. In addition, 69.2% of the formulation-changed patients and 75.0% of newly prescribed patients stated that they could easily self-administer OD film; 61.5% of formulation-changed patients and 66.7% of newly prescribed patients indicated that they felt more comfortable using an OD film; and 28.0% of all patients addressed the negative opinions on OD film’s ease in oral administration. Conclusion: This study examined 25 patients’ OD film experience, and suggested that the film form improved usability and portability of the medication. [ABSTRACT FROM AUTHOR]

Sildenafil citrate (Viagra®) is used to treat male erectile dysfunction; however, little is known about the effects of sildenafil overdose and intoxication. We report a patient who presented with cerebral infarction and rhabdomyolysis after intentional sildenafil intoxication. A 61-year-old man visited the Emergency Department complaining of dysarthria about 1 h after taking more than 30 sildenafil tablets with the intention to commit suicide. Dysarthria and dizziness were observed, but there were no other neurological symptoms. The creatine kinase level was elevated to 3118 U/L, and the patient was diagnosed with rhabdomyolysis. Brain magnetic resonance imaging revealed multiple scattered acute cerebral infarctions in both midbrain artery branches. At 4 h post-intoxication, the dysarthria had improved and we initiated dual antiplatelet therapy for cerebral infarction. Emergency physicians should be able to anticipate and treat complications like cerebral infarction and rhabdomyolysis after sildenafil intoxication. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Phosphodiesterase 5 inhibitors (PDE5Is) and other more invasive options merely provide symptomatic relief rather than a permanent improvement in erectile dysfunction (ED), whereas the long-term improvement in ED via low-intensity extracorporeal shockwave therapy (Li-ESWT) has been confirmed. So far, no comparative study of sildenafil versus Li-ESWT has been conducted with respect to treatment satisfaction. Objective: In this study, we aim to compare erectile function status and satisfaction rates in patients who received sildenafil or Li-ESWT for ED. Methods: Patients complaining of ED were considered candidates. Participants chose to enter one of two active treatment groups according to their treatment intention—either a 9-week Li-ESWT regimen or 100 mg on-demand sildenafil. The erectile function was evaluated using the erectile function domain of the International Index of Erectile Function questionnaires (IIEF-EF), while the treatment satisfaction was evaluated using the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaires (EDITS). Results: We enrolled 72 participants in the study (42 in the Li-ESWT group and 30 in the sildenafil group). Patients in both groups were young men. Four weeks after the last session, the IIEF-EF score for Li-ESWT and sildenafil was 16.3± 5.5 and 18.3± 6.5 (P >  0.05), respectively. The total EDITS index of the patient version and the partner version were similar in the two groups. Among EDITS questions measuring overall satisfaction and efficacy duration, the score was higher in the Li-ESWT group. Conclusion: We found that Li-ESWT may have better satisfaction than on-demand sildenafil for young ED patients. However, further studies are needed to determine the factors influencing satisfaction. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of female sexual arousal disorder (FSAD) requires that individuals experience clinically significant distress from their symptoms. Pre-trial content validity investigations were conducted by the sponsor to understand how women with FSAD best described their distress associated with this female sexual dysfunction (FSD) diagnosis. Objective: Responses to the Female Sexual Distress Scale – Desire, Arousal, Orgasm (FSDS-DAO) survey among healthy premenopausal women enrolled in a Phase 2b, exploratory, randomized, placebo-controlled, double-blind study of Sildenafil Cream, 3.6% for FSAD treatment (NCT04948151). Methods: After informed consent, enrollment diagnoses for each participant were established during a one-on-one clinical interview with independent experts. Baseline assessments were measured after a one-month, single-blind, placebo, run-in period. Participants were then randomized to Sildenafil Cream, 3.6% (n=101) versus Placebo (n=99) and used the investigational product (IP) as needed at home for 12 weeks, with monthly in-clinic assessments. The change from baseline at week 12 in question 14 (Q14) of the FSDS-DAO was a co-primary efficacy endpoint. All 15 FSDS-DAO questions begin with "How often did you feel, in the past 30 days" with a Likert score of 0 (Never) to 4 (Always). Results: Although changes from baseline at week 12 in FSDS-DAO Q14 responses were not different among active versus placebo users in the intent-to-treat population (p=0.84) or the future target population (women with FSAD only or primary FSAD with secondary hypoactive sexual desire disorder (HSDD)) (p=0.95), responses to several FSDS-DAO questions, showed reduced sexual distress among Sildenafil Cream, 3.6% users (Table 1). While Q14 asked specifically about concerns with sexual arousal, the other 5 questions asked about generalized sexual distress, using verbiage more congruent with pre-trial content validity investigations. Post-trial psychometric validation studies selected question 5 as the most appropriate for measuring sexual distress among this population. Conclusions: Data from this exploratory trial support that women with a diagnosis of FSAD only or primary FSAD with secondary HSDD experienced reduced sexual distress after receiving Sildenafil Cream, 3.6%. Disclosure: Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Science and Technologies. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and Strategic Science and Technologies. [ABSTRACT FROM AUTHOR]

Background and Objective: Vericiguat is approved for the treatment of patients with heart failure with ejection fraction < 45%. Sildenafil, indicated for the treatment of erectile dysfunction, is a potential co-medication in male patients. This study investigated the safety and tolerability of co-administration of vericiguat and sildenafil in healthy volunteers. Methods: This was a single-center, randomized, placebo-controlled, parallel-group study in 32 healthy white male volunteers. Participants received vericiguat 10 mg or placebo once daily for 16 days. Both groups received single doses of sildenafil (25 mg, 50 mg, and 100 mg) on days 13–15. Safety, hemodynamic changes, and pharmacokinetic effects were assessed. Results: All subjects in the vericiguat group and seven (43.8%) in the placebo group reported one or more treatment-emergent adverse events, all of mild or moderate intensity. Decreases in seated blood pressure (≤ 5.4 mmHg) with the vericiguat-sildenafil combination compared with placebo-sildenafil were small and there was no evidence of a sildenafil dose-related effect. Standing blood pressure and standing and seated heart rate were similar between treatment groups. Co-administration of sildenafil did not affect vericiguat pharmacokinetics. A mild increase in sildenafil exposure (≤ 22%) when co-administered with vericiguat was observed. Conclusions: Adding single doses of sildenafil to vericiguat 10 mg once daily at steady state was well tolerated and produced a minimal reduction in seated blood pressure (≤ 5.4 mmHg) compared with administration of sildenafil alone. There was no effect of sildenafil on vericiguat pharmacokinetics, and an increase in sildenafil exposure with vericiguat co-administration was not clinically relevant. Clinical Trial Registration: EudraCT no. 2015-004997-14. Plain Language Summary: Vericiguat is approved for the treatment of patients with heart failure with reduced ejection fraction. Sildenafil is a treatment for erectile dysfunction. This study investigated whether sildenafil was safe to use in individuals treated with vericiguat. In total, 32 healthy white male volunteers were randomly allocated to receive either vericiguat 10 mg or placebo once daily for 16 days. Both groups received single doses of sildenafil (25 mg, 50 mg, and 100 mg) on days 13–15. Co-administration of single doses of sildenafil and vericiguat 10 mg was well tolerated. All side effects were of mild or moderate intensity, and the addition of sildenafil to vericiguat had a minimal effect on blood pressure. Giving these drugs together did not alter the way either drug was absorbed, distributed, or eliminated by the body to a clinically relevant extent. [ABSTRACT FROM AUTHOR]

Background: The increasing distribution of Substandard and Falsified Medical Products is a well-known health risk. The quantity of these medicines sent to consumers is not known, and it can only be accurately estimated with a specific sample collection study. These consignments ordered via mail from illegal online sources pose a great health risk on the population. Methods: We used an observation-based cross-sectional study in order to obtain accurate data regarding the number of medicinal shipments from dubious origin. We collected data on-site to assess the number of Substandard and Falsified Medical Products arrived in Hungary via postal services in 2020. Results: The therapeutic category (according to the Anatomical Therapeutic Chemical Classification (ATC) system of the WHO) of the most frequently shipped products contained active ingredients for treating erectile dysfunction. These substances were sildenafil (G04BE03), tadalafil (G04BE08), and other analgesics and antipyretics, such as anilides (N02BE). In 2020 we estimated that the real Defined Daily Dose of SFMP was 1.2 DDD per 1000 inhabitants per day. This value is equivalent to one third of Hungary's opioid analgesic use. We also calculated that the average exposure was approximately 4 ampoules per day and 40 oral preparations per day (without DDD value) for 1000 people in Hungary. Conclusions: This study accurately estimates the number of consignments received by post containing Substandard and Falsified Medical Products, and determines the quantity per 1000 persons per day expressed in DDD. This parameter may be used as a benchmark that helps more detailed research in the future. [ABSTRACT FROM AUTHOR]

Background and objectives: Erectile dysfunction (ED) is the inability to achieve or sustain an erection for satisfactory sexual activity Aim of work: evaluate sexual functions of patients with erectile dysfunction and their female partners across different ED therapies. Patient and methods: A total of 100 married couples (the males age range from 51-60 years, the females age range from 38-45 years) were included in the study. Results: female partners of ED patients who received sildenafil did not demonstrate improvements in frequency of pain during vaginal penetration, confidence of becoming aroused, frequency of satisfaction with arousal and maintenance of lubrication. Concolusion: This study linked treatment-related improvement in men's erectile function with observed improvements in women partner's sexual function mainly with Sildenafil. [ABSTRACT FROM AUTHOR]

Central serous chorioretinopathy (CSCR) is a retinal disease that may be complicated by the development of serous retinal pigment epithelial detachment (PED). The exact molecular mechanisms of CSCR have remained uncertain as well as there is no effective medical therapy. Herein, we describe a case of a 43-year-old male suffering from chronic CSCR with PED and visual acuity reduction (20/40) that showed improvement in visual acuity (20/25) and metamorphopsia 2 weeks after daily intake of 20 mg sildenafil tablets. Optical coherence tomography (OCT) scan showed resolution of PED with residual degeneration of the photoreceptor inner and outer segment layer and retinal pigmented epithelium. The patient continued treatment with sildenafil 20 mg for 2 months. Six months after the discontinuation of therapy, visual acuity was maintained, with absence of PED at OCT. Our case supports the hypothesis that phosphodiesterase type 5 (PDE-5) inhibitors may be an alternative in the treatment of patients with CSCR, alone or combined with other medications. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A recent study suggests that the drug sildenafil, commonly known as Viagra, may reduce the risk of developing Alzheimer's disease. The study found that individuals who used sildenafil had a 69% reduced risk of Alzheimer's disease compared to non-users. However, there are limitations to the research, such as the reliance on prescription records and the inability to determine if the medication was actually used. The study raises the question of whether drugs developed for one condition can be repurposed for another, and there is growing interest in exploring this possibility. While the findings are intriguing, further research, including randomized controlled trials, is needed to confirm the potential benefits of sildenafil in preventing Alzheimer's disease. [Extracted from the article]

Objective: To evaluate sexual functions of patients with erectile dysfunction (ED) and their female partners. Methods: A total of 90 consecutive ED patients who received different ED therapies and their partners and 90 consecutive controls and their partners were divided into four groups. All participants were evaluated by the 15-item international index of erectile function and the Arabic version of female sexual function index (Ar-FSFI). Results: All ED patients who received sildenafil demonstrated significant improvements of their erectile function compared to baseline. Their partners did not demonstrate improvements in frequency of pain during vaginal penetration (3.86 ± 0.58, 3.93 ± 0.45, p = 0.477), confidence of becoming aroused (3.86 ± 0.58, 3.93 ± 0.45, p 0.477), frequency of satisfaction with arousal (3.07 ± 0.37, 3.03 ± 0.49, p 0.712), and maintenance of lubrication (4.37 ± 0.49, 4.23 ± 0.73, p 0.354). All ED patients who received quadmix demonstrated significant improvements of their erectile function compared to baseline. Their partners did not demonstrate improvements in desire level (2.6 ± 0.67, 2.63 ± 0.85, p = 0.869) and lubrication maintenance (3.53 ± 0.82, 3.47 ± 0.82, p = 0.423). Finally, All ED patients who underwent semi rigid penile implant demonstrated significant improvements of their erectile function compared to baseline. Their female partners demonstrated significant improvements in all items of FSFI-19 compared to baseline except the frequency of pain during vaginal penetration (3.86 ± 0.58, 3.93 ± 0.45, p = 0.477), confidence of becoming aroused (3.86 ± 0.58, 3.93 ± 0.45, p = 0.477), frequency of satisfaction with arousal (3.07 ± 0.37, 3.03 ± 0.49, p = 0.712), and maintenance of lubrication (4.37 ± 0.49, 4.23 ± 0.73, p = 0.354). Conclusions: Sexual functions of ED males significantly improved after ED therapies. Nevertheless, some sexual functions of their partners were not positively impacted. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the presence of undeclared sildenafil, tadalafil, and vardenafil in food supplements (FSs) for erectile dysfunction. The presence of sildenafil, tadalafil, and vardenafil was determined using the generated ultraviolet (UV)-spectra and mass-spectrometry (MS)-spectra as well as chromatograms produced by the photodiode array (PDA)-detector and ion trap MS-detector. The results were processed by Xcalibur ver. 2.0.7. Fourteen of the 20 analyzed FSs contained undeclared ingredients. Sildenafil was present in 12 of them. Many violations and discrepancies between the label information and the real composition of the FS were identified. 70% of the samples contained undeclared ingredients of an erectile dysfunction medicinal product. The quantities varied within broad limits from 2 mg per tablet to 116.55 mg per tablet. Sildenafil was present in amounts exceeding 16.55 mg that is the maximum recommended dose, thus creating risk of overdose. Besides that, food supplements adulterated with sildenafil analogues are a health risk for consumer's health as there is no evidence of modified sildenafil toxicity. All analyzed FSs were claimed to be 100% natural, not provoking side effects. No information for any FS contained indications of age limits or risk for interaction with other FSs or medical products. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) has a significant impact on the quality of life of patients. Xybilun® (IBSA Pharma SAS, France) is a new formulation of sildenafil in an orodispersible film (ODF). This study aims to assess the response rate (RR), satisfaction with, and safety of sildenafil-ODF in daily practice in France. Patients aged ≥18 years with ED were included in four groups: Group 1 mild, Group 2 moderate, Group 3 severe ED, according to the International Index for Erectile Function (IIEF)-6 subscore, never treated with phosphodiesterase inhibitors (PDE)5-I; Group 4, patients previously treated with another PDE5-I. Patients were evaluated at baseline (V1), one (V2), and three (V3) months. The RR and satisfaction were assessed using the IIEF-6 subscore questionnaire, a 5-point Likert scale, and a Global Assessment Question (GAQ). The primary endpoint for Groups 1 to 3 was the RR according to Rosen criteria at V3 compared to V1. For Group 4, the primary endpoint was the RR, defined as the satisfaction compared with previous treatment. Secondary endpoints were the RR at V2 compared to V1, the evolution of IIEF-6 and IIEF-15 scores, dose adjustment, satisfaction, convenience, and safety. One hundred and five patients were enrolled, 83 analysed. The RR at V3 was 100% (Group 1); 75% (Group 2); 65.2% (Group 3); and 84.2% (Group 4). The overall RR was 78.3%. Secondary parameters confirmed the satisfaction with sildenafil-ODF, with 81.6% of patients very satisfied at V3. No Serious Adverse Events (SAEs) were observed. In conclusion, sildenafil-ODF seems beneficial for patients irrespective of the severity of the ED. This study confirms in the context of daily clinical practice the satisfaction of patients with sildenafil-ODF. Data suggest that the availability of the intermediate dose of 75 mg could add greater flexibility to the therapy. [ABSTRACT FROM AUTHOR]

Phosphodiesterase-5 inhibitors (PDE5Is) represent a group of drugs that are registered for the treatment of erectile dysfunctions predominantly, but recently also for treatment of pulmonary hypertension and benign prostatic hypertrophy. However, more and more research deals with possible antitumor potential of PDE5Is in different types of cancers, including prostate cancer. Prostate cancer represents the one of the most common carcinoma in the male population, whose incidence is continuously increasing. Early detection combined with radical prostatectomy increases the survival rate, but also it is necessary to keep in mind the quality of life of patients undergoing prostatectomy in light of bladder control and erectile function. Authors of various clinical studies presented the results that often lead to totally opposing conclusions. For example, Chavez and colleagues have shown that use of PDE5Is in men with erectile dysfunction decreases the risk of developing prostate cancer, while, on the other hand, Michl and colleagues pointed out the adversely effect of PDE5Is on biochemical recurrence after bilateral nerve sparing radical prostatectomy. In that sense, the aim of this review was to present as many as possible of existing results dealing with of action of PDE5Is in the field of prostatic carcinoma. Taking into account all presented data, it can be concluded that eff ect of PDE5Is on formation, development and outcome of treatment in patients with prostate carcinoma is very intriguing question, whose response requires additional both experimental and clinical research. [ABSTRACT FROM AUTHOR]

Schumanniophyton magnificum is a medicinal plant used to manage many ailments including malaria, skin diseases, parasitic infections, male sexual dysfunctions, female infertility and typhoid fever. However, no scientific investigation has been made for its folkloric use by the "Baka" Pygmies of Cameroon as an aphrodisiac. To investigate the aphrodisiac and androgenic activities of the aqueous extract of the roots of Schumanniophyton magnificum in male rats and analyze the phytoconstituents by UHPLC/MS. Twenty-five male rats of 16-weeks old were divided into 5 groups and orally treated for 30 days with distilled water (10 ml/kg), or sildenafil citrate (5 mg/kg), or the aqueous extract of Schumanniophyton magnificum (43 mg/kg, 86 mg/kg and 172 mg/kg). The sexual behaviour parameters were monitored on day 1 and 30 by pairing male rats to receptive females. At the end of the experiment, rats were killed and the blood and reproductive organs were collected for histological sectioning, sperm analysis and biochemical analysis. The presence of phytoconstituents and their structures were revealed by UHPLC/MS. The plant extract significantly increased the mount, ejaculation and intromission frequencies in comparison to those in the normal control group; and significantly doubled the serum testosterone levels (2.15 ± 0.70 ng/ml) compared to the normal control group. UHPLC/MS of the aqueous extract of Schumanniophyton magnificum identified 7 major compounds such as Schumanniofioside A, Noreugenin and Rohitukine, with antioxidant and antibacterial activities. The plant extracts significantly increased the penile nitric oxide levels (P <0.05). These results were similar to those obtained after administration of sildenafil citrate. The aqueous extract of Schumanniophyton magnificum could be an alternative for erectile dysfunction management. [Display omitted] • The aqueous extract of S. magnificum significantly enhanced sexual parameters in male Wistar rats. • UHPLC-MS/MS revealed 7 major phytoconstituents identified in the aqueous extract. • The extract significantly increased testosterone and penile nitric oxide levels at 43 and 86 mg/kg, bw. • Oral administration of the extract had no adverse effects on the reproductive organs. • The extract exhibits androgenic and aphrodisiac properties. [ABSTRACT FROM AUTHOR]

Introduction: Quantifying the change in the mean number of satisfactory sexual experiences (SSEs) is an efficacy endpoint recommended by the US Food and Drug Administration in studies of treatments for female sexual dysfunctions (FSD), including female sexual arousal disorder (FSAD). Objective: Post-hoc analysis of sexual experiences in a study of Sildenafil Cream, 3.6% for treatment of FSAD Methods: Phase 2b, exploratory, randomized, placebo-controlled, double-blind study of Sildenafil Cream, 3.6% among premenopausal women with FSAD (NCT04948151). Following a baseline, single-blind, placebo, run-in period, participants were randomized and used investigational product (IP) at home for 12 weeks. Between monthly, in-clinic assessments, participants answered questions in an electronic diary (eDiary), within 24-hours of each sexual experience. Sexual experiences were categorized as "Partnered" versus "By Myself" and "Satisfactory" versus "Not Satisfactory". eDiary question 11 (Q11) asked "Were conditions appropriate for satisfactory sexual activity (enough time, no distractions, etc.)?". Changes from baseline in the mean number of SSEs was a secondary efficacy endpoint. The Orgasm domain (questions 22-24) of the Sexual Function Questionnaire (SFQ28) was an exploratory efficacy endpoint. Un-partnered women and women with sexual partners who did not sign informed consent were enrolled in the study, but in these cases (n=15), IP was only used in solo sexual experiences. Results: Sildenafil Cream users had more sexual experiences and more un-partnered sexual experiences during the double-blind treatment period compared to Placebo Cream users. Sildenafil Cream users were significantly more likely to engage in sexual experiences even when conditions were not appropriate for a satisfactory experience. Although, the change from baseline in the mean number of SSEs at week 12 decreased during solo, un-partnered sexual experiences for both product groups (-0.12±0.27 for Sildenafil versus -0.04±0.32 for Placebo, p=0.85), during the double-blind treatment period, Sildenafil Cream users reported significantly higher proportions of SSEs during un-partnered sexual experiences (197/261, 75.5%) compared to Placebo users (116/187, 62.0%) (p=0.002). Despite Sildenafil Cream users engaging in a sexual experience more frequently when conditions were not appropriate, the proportion of SSEs during these events when Q11="No" were not different between active (17/59, 28.8%) versus placebo (8/25, 32.0%) users (p=0.77). Finally, un-partnered women and women with un-enrolled sexual partners, who by definition had only solo sexual experiences, had an increase from baseline in their SFQ Orgasm at week 12 with Sildenafil use (2.58±1.13) versus Placebo users in this subset, who had decreases in this score (-0.34±1.13) (p=0.13). Conclusions: These data support that Sildenafil Cream 3.6% enhanced solo, un-partnered sexual experiences, which represented approximately 1 in 5 events in this FSAD treatment study. Disclosure: Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Science and Technologies LLC Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and Strategic Science and Technologies LLC. [ABSTRACT FROM AUTHOR]

Sildenafil (Viagra) is a vasodilator mainly used in the treatment of erectile dysfunction. Atrial or ventricular fibrillation may rarely occur as a side effect during sildenafil therapy. Although changes in inward rectifier potassium currents including I K1 are known to contribute to the pathogenesis of fibrillation, the effect of sildenafil on I K1 has not been studied. In experiments, Ba2+ is used as a specific inhibitor of I K1 at high concentrations (usually 100 µM). Being an environmental contaminant, it is also present in the human body; Ba2+ plasmatic concentrations up to 1.5 µM are usually reported in the general population. This study was primarily aimed to investigate changes of I K1 induced by sildenafil in a wide range of concentrations (0.1–100 µM). Additionally, the effect of combination of sildenafil and Ba2+ at selected clinically-relevant concentrations was tested, at 0.1 µM both on I K1 and on the action potential duration (APD). Experiments were performed by the whole-cell patch-clamp technique on enzymatically isolated rat ventricular cardiomyocytes, mostly at 23°C with the exception of APD measurements which were performed at 37°C as well. Sildenafil caused a significant, reversible, and concentration-dependent inhibition of I K1 that did not differ at −50 and −110 mV. Simultaneous application of sildenafil and Ba2+ at 0.1 µM revealed a massive inhibition of both inward and outward components of I K1 (this synergy was missing at other tested combinations). The combined effect at 0.1 µM (45.7 ± 5.7 and 43.0 ± 6.9% inhibition at −50 and −110 mV, respectively) was significantly higher than a simple sum of almost negligible effects of the individual substances and it led to a significant prolongation of APD at both 23 and 37°C. To our knowledge, similar potentiation of the drug-channel interaction has not been described. The observed massive inhibition of I K1 induced by a combined action of the vasodilator sildenafil and environmental contaminant Ba2+ at a low concentration and resulting in a significant APD prolongation may contribute to the genesis of arrhythmias observed in some patients treated with sildenafil. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of avanafil as compared with sildenafil in the management of patients with erectile dysfunction. Methods: It was a prospective, randomized, double‐blind, two‐arm, active‐controlled, parallel, multicenter, non‐inferiority clinical study carried out in patients with erectile dysfunction for at least 3 months and International Index of Erectile Function – Erectile Function domain score of <26 at enrolment. Results: A total of 220 patients were randomized to receive either avanafil tablets 100 mg or sildenafil tablets 50 mg in 1:1 ratio. After 4 weeks of treatment, 40.0% of patients in the avanafil group and 45.6% of patients in the sildenafil group required dose escalation to a high dose (avanafil 200 mg/sildenafil 100 mg). The difference in the mean change of International Index of Erectile Function – Erectile Function score from baseline in the two groups increased from week 4 (1.1, 95% confidence interval −0.2 to 2.5) to week 8 (1.4, 95% confidence interval 0.1–2.7) and week 12 (2.1, 95% confidence interval 0.8–3.5), showing non‐inferiority at week 4, and superiority at week 8 and week 12. Avanafil showed a faster onset of action as shown by a significantly better response to modified Sexual Encounter Profile 1 in the avanafil group (84.8%) as compared with that in the sildenafil group (28.2%; P < 0.001). Both avanafil and sildenafil were well tolerated by all the patients in the study; the most common adverse event reported during the study was headache in both the groups. Conclusion: Avanafil is superior to sildenafil in improving the International Index of Erectile Function – Erectile Function domain score at the end of 12 weeks of treatment with the added advantage of faster onset of action. [ABSTRACT FROM AUTHOR]

Patients presenting to the emergency department with priapism require immediate evaluation and treatment. Priapism is a urological emergency that carries the risk of erectile dysfunction if not managed in a timely manner. Therefore, it is important for providers to be able to identify and manage these patients emergently. Priapism has various causes, and knowing the difference between high-flow and low-flow priapism will help determine the appropriate patient management. Although the prevalence of priapism is thought to be low, there have been increasing reports over the years linked to new drugs used for the treatment of erectile dysfunction (Roghmann et al., 2013). For this reason, it is imperative that providers understand the etiology behind the different causes of priapism. Using a case of drug-induced priapism as an exemplar, this article discusses the epidemiology, etiology, and management of priapism conditions. [ABSTRACT FROM AUTHOR]