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This article is an up-to-date review of 112 unapproved phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in sexual enhancement dietary supplements and other products from 2003 to July 2023. Seventy-five of these unapproved PDE-5i are analogues of sildenafil (67%), followed by 26 analogues of tadalafil (23%), 9 analogues of vardenafil (8%) and 2 other type of compounds (2%). The products have been formulated in various packaging, primarily in capsule, tablet, and powder forms. Common screening techniques allowing detection of such analogues include high performance or ultra-high performance liquid chromatography in tandem with ultra-violet detector (HPLC-UV or UPLC-UV) (50%) and thin-layer chromatography in tandem with ultra-violet detection (TLC-UV) (7%). Screening by mass spectrometry (MS) is relatively less common with the use of single-, triple-quadrupole or time-of-flight (TOF) mass spectrometers (9%). Meanwhile, the combined detection by UV-MS has been recorded at 10% usage. Screening by proton nuclear magnetic resonance spectroscopy (NMR) (11%) has also been applied. For compound characterization, i.e. structural elucidation, NMR spectroscopy has been preferred (100 out of 112 compounds), followed by high-resolution mass spectrometry (HRMS) (74 out of 112 compounds) and Fourier-transform infrared spectroscopy (FTIR) (44 out of 112 compounds). Over the past two decades, analytical technology has been evolving with enhanced sensitivity and resolution. Despite this, structural elucidation of the new emerging analogues in adulterated dietary supplements remains a challenge, especially when the analogues involve complex structural modification. Therefore, the above-mentioned techniques may not be adequate to characterize the analogues. Additional work involving chiroptical methods, two-dimensional (2D) NMR experiments and X-ray crystallography are likely to be required in the future. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) is an emerging pandemic caused by a novel coronavirus (SARS-CoV-2). Since December 2019 the new virus has spread all over the world and has become a major health problem also because of the public measures that could affect people’s sexual activity. We report a case of a 35-year-old married male admitted to the andrology outpatient clinic in July 2021 because of sudden onset erectile dysfunction (ED). The diagnostic workup showed no risk factor for ED, normal levels of testosterone, increased levels of endothelial dysfunction markers, such as CRP (C-Reactive Protein) and Endothelin-1, and reduced Vitamin D (VD) levels. Dynamic penile duplex ultrasound (D-PDU) revealed dysfunctional penile arterial flow. The five-item International Index of Erectile Function (IIEF-5) and the Short-Form Health Survey (SF-36) showed a reduction in all domain scores. The patient, initially unresponsive to the high dose oral phosphodiesterase 5 inhibitors (PDE-5is), was treated with vitamin-D and then submitted to LI-SWT (low intensity shockwave treatment), with a progressive clinical benefit at the 12-month follow-up. After 18 months, hormone levels persisted in normal ranges, with a consistent reduction in CRP and Endothelin-1. Additionally, IIEF-5, SF-36 and arterial flow significantly improved over the follow-up period. Thus far, the erectile function was restored and the patient is no more treated with PDE-5i.

The coronavirus disease 2019 (COVID-19) is an emerging pandemic caused by a novel coronavirus (SARS-CoV-2). Since December 2019 the new virus has spread all over the world and has become a major health problem also because of the public measures that could affect people's sexual activity. We report a case of a 35-year-old married male admitted to the andrology outpatient clinic in July 2021 because of sudden onset erectile dysfunction (ED). The diagnostic workup showed no risk factor for ED, normal levels of testosterone, increased levels of endothelial dysfunction markers, such as CRP (C-Reactive Protein) and Endothelin-1, and reduced Vitamin D (VD) levels. Dynamic penile duplex ultrasound (D-PDU) revealed dysfunctional penile arterial flow. The five-item International Index of Erectile Function (IIEF-5) and the Short-Form Health Survey (SF-36) showed a reduction in all domain scores. The patient, initially unresponsive to the high dose oral phosphodiesterase 5 inhibitors (PDE-5is), was treated with vitamin-D and then submitted to LI-SWT (low intensity shockwave treatment), with a progressive clinical benefit at the 12-month follow-up. After 18 months, hormone levels persisted in normal ranges, with a consistent reduction in CRP and Endothelin-1. Additionally, IIEF-5, SF-36 and arterial flow significantly improved over the follow-up period. Thus far, the erectile function was restored and the patient is no more treated with PDE-5i. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between phosphodiesterase-5 inhibitors (PDE-5i) and hearing impairment adverse events (HIAEs) while providing an overview of the characteristics of drug-related HIAEs., Research Design and Methods: We conducted a detailed pharmacovigilance analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, covering 2004 to 2022. By calculating the reporting odds ratio (ROR) and the information component (IC), we identified signals that indicate the association between PDE-5i use and HIAEs., Results: Among the 191,398 reports related to PDE-5i, we identified 2,608 cases of HIAEs. Signals were observed for both PDE-5i monotherapy and polytherapy, indicating combinations of drugs. Avanafil exhibited the strongest signal (ROR: 4.35, 95% CI: 2.56-7.41, IC: 2.09, 95% CI: 0.10-3.51), while vardenafil showed the weakest signal (ROR: 2.69, 95% CI: 2.21-3.28, IC: 1.14, 95% CI: 0.74-2.04). Sildenafil had the highest reported cases (ROR: 3.03, 95% CI: 2.82-3.24, IC: 1.57, 95% CI: 1.34-1.80)., Conclusion: These findings highlight a significant correlation between PDE-5i use and HIAEs, emphasizing the need for careful evaluation in clinical practice and providing appropriate guidance to patients before initiating treatment.

• Strategy for the screening analysis of falsified samples was developed. • ATR proved to be appropriate technique for PDE-5i identification in complex matrix. • Complementarity between ATR-FTIR and XRPD was demonstrated. • Developed strategy was successfully introduced into routine analysis. Falsified drugs are a growing problem and a great threat all over the world. Searching for easy, fast, not expensive and reproducible methods for identification of active pharmaceutical ingredients (APIs) is an important issue. The application of ATR-IR technique for identification of phosphodiesterase-5 inhibitors (PDE-5i) in falsified products from the Polish market has been demonstrated. Furthermore, the strategy of confirmation of the product's originality in a quick and easy way has been developed. The advantages of this application are: exceptional simplicity, very short measurement time, high selectivity in relation to structurally similar substances and almost no sample preparation. After validation, developed strategy has been successfully introduced into routine analysis. [ABSTRACT FROM AUTHOR]

Background: Sildenafil and tadalafil are recommended firstline treatments for erectile dysfunction (ED). Sildenafil was legally reclassified to a ‘pharmacy’ medicine in the UK in 2018. Aim: To assess the prescribing patterns and costs associated with prescribing of ED drugs in England, and to investigate the link between prescribing and deprivation, regional demography, and legal reclassification. Design & setting: Analyses were conducted of publicly available government data from various sources pertaining to primary care prescribing and demographics in England. Method: Prescribing and cost data from January 2009 to November 2019 were extracted and adjusted for inflation, male populations, and regional deprivation. Results: Between 2009 and 2019 the rate of prescribing, measured as the number of items per 1000 men, increased by 110%. In 2019, the rate of prescribing of ED medicines in the most deprived areas was 21.0% higher than the rate observed in least deprived areas. The northern regions of England approximately had a 50% higher rate of prescribing compared with London. A 1.3% annual increase in the number of prescription items was observed between 2018 and 2019 for Sildenafil, with a 5.8% increase observed from 2017–2018. Conclusion: The two-fold increase in the rate of primary care prescriptions in the past 10 years suggests that more men are being screened for, or seeking help for, ED. The higher rate of prescribing offers opportunity for monitoring of linked risk factors, such as diabetes mellitus, dyslipidaemia, and vascular disorders, in deprived populations. Reclassification of sildenafil had a modest impact on prescribing practices.

With an increase in the detection of structural and functional analogues of phosphodiesterase type 5 inhibitors (PDE-5i) in dietary supplements (DS) and foods, public health is threatened. Some products advertise natural ingredients despite containing PDE-5i that can cause serious adverse effects on human health. To avoid detection during routine screening, novel PDE-5i have been synthesised and added to DS and foods. The purpose of this study was to detect, identify, and quantify 94 PDE-5i and related compounds in DS and foods. Furthermore, the study investigated the detection cases and compared them by sample type, formulation, and compounds. The HPLC and LC-MS/MS methods were validated for limit of detection (LOD), limit of quantification (LOQ), linearity, and recovery in solid and liquid type samples. Both HPLC and LC-MS/MS showed satisfactory results, which were in conformance with the ICH guidelines. A total of 404 samples, including DS (99), and foods (305) were purchased from online and offline markets. Samples divided into 5 types of formulation were analysed; tablet, capsule, pilula (herbal medicine pill), powder and liquid type. Of these 130 samples (47 of 99 DS, and 83 of 305 foods) contained one or more PDE-5i or related compounds. Among the five types of formulation, the tablet type showed the highest detection rate (61.1%) in DS, whereas the capsule type showed the highest detection rate (53.8%) in food samples. This study will be helpful for monitoring illegal ED-related products, providing information to consumers, and ultimately contributing to protecting public health. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Sexual dysfunction is a common toxicity following radiotherapy, similar to men undergoing radical prostatectomy, but the etiology is different. The pathophysiology of radiation-induced sexual dysfunction is multi-factorial, and the toxicity is a major cause of impaired quality of life among long-term prostate cancer survivors. Management of a patient's sexual function during and after radiotherapy requires multidisciplinary coordination of care between radiation oncology, urology, psychiatry, pharmacy, and dermatology. This review provides a framework for clinicians to better understand prostatic radiotherapy-induced sexual dysfunction diagnosis, evaluation, and a patient-centered approach to toxicity preventive strategies and management. [ABSTRACT FROM AUTHOR]

To date, there are 80 synthetic PDE-5i found as adulterants in dietary supplements. Analogues of sildenafil remain as the top list with 50 (62%) and are followed by analogues of tadalafil, 21 (26%), analogues of vardenafil, 7 (9%) and others, 2 (3%). The sildenafil group can be sub-categorized into sulphonamide-bonded (24, 48%), acetyl-bonded (11, 22%), carbonyl or thiocarbonyl-bonded (8, 16%) and other types (7, 14%) based on the functional group linked to pyrazolopyrimidine-one moieties. Meanwhile, analogues of tadalafil have become popularly found as adulterants in dietary supplements like beverages and herbal extracts from 2015 to 2016. The uptrend has been observed with the increase in number and complexity with more trans -oriented and dimerized tadalafil analogues being reported. Interestingly, there is no much increase for analogues of vardenafil. About two thirds of analogues have been reported from the Asian countries (67%), followed by Europe (22%) and North America (11%). South Korea and Singapore have reported the most number of analogues with a total number of 40 (50%). One plausible contributing factor to this trend is the convenient purchase of sexual enhancement dietary supplements, especially the on-line purchase. In terms of analytical methodologies, high performance liquid chromatography (HPLC) hyphenated to ultra-violet (UV) and/or mass spectrometry (MS) detection have been preferred in the screening analysis, i.e. 70 out of 77 compounds have been analysed by HPLC-UV. In addition, the electrospray ionization multistage fragmentation experiments (ESI-MS n ) for acquiring low- and high-resolution mass spectra have been successfully applied to detect and quantify PDE-5i in adulterated products simultaneously. Nuclear magnetic resonance (NMR) is another important technique in the structural elucidation of novel analogues. [ABSTRACT FROM AUTHOR]

Résumé La prise en charge de la dysfonction érectile (DE) a été bouleversée par la mise sur le marché des inhibiteurs de la phosphodiestérase V (iPDE-5). Leur utilisation est maintenant bien validée et codifiée. Les iPDE-5 ont largement fait la preuve de leur innocuité et de leur efficacité, y compris dans des populations vulnérables et poly-morbides ou poly-médiquées, chez lesquelles la prévalence des DE est importante et mal supportée. Ils représentent aujourd’hui le traitement de choix en première intention de la dysfonction érectile, en l’absence de contre-indication à leur utilisation. Nous reprenons dans cet article les recommandations du comité concernant les règles de prescription et d’encadrement de la prescription des différents iPDE-5. Summary Treatment of erectile dysfunction (ED) has been turned on its head by the market approval of Phosphodiesterase V inhibitors (iPDE-5), now fully validated and codified. iPDE-5 have proven their safety and their effectiveness, including for vulnerable populations or polymorbid or polymedicated populations, for whom the prevalence of ED is high and poorly tolerated. Today they are the best first-line treatment for ED, in the absence of medial contraindication. This article presents the recommendations of the committee concerning the guidelines for prescribing and managing the prescription of the various types of iPDE-5 drugs. [ABSTRACT FROM AUTHOR]

Pulmonary artery hypertension (PAH) refers to several subgroups of disease in which the mean pulmonary artery pressure (mPAP) is elevated to more than 25 mm Hg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR) > 3 Wood units as confirmed by right heart catheterization. The prevalence and geographic distribution of PAH vary depending on the type and etiology of the disease. Despite enormous efforts in the research and development of therapeutic agents in the last twenty years, the disease remains relatively incurable and the overall prognosis remains guarded. Median survival for an untreated patient is 2.8 years. In the last three decades, there have been dramatic advances in understanding the molecular mechanisms and signaling pathways involved in the disease, resulting in emerging new treatment strategies. In the following pages, we will review currently approved treatments for PAH, as well as a new generation of investigational drugs. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). Patients and methods: The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, penile colour Doppler ultrasonography (CDUS) for peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) with an ICI test using 0.25mL of trimix of papaverine, PGE1 and phentolamine. Testosterone, prolactin and cholesterol levels were assessed. Patients received 25mg sildenafil daily for 8 weeks, combined with twice weekly ICI with 0.25mL of trimix. After treatment, the Erection Hardness Score (EHS), penile CDUS with ICI and ED Inventory of Treatment Satisfaction were assessed. Results: The mean (SD) SHIM-5 score before treatment was 8.3 (0.5) in 15 of the 40 men and 6.3 (0.4) in 25. Penile haemodynamics were normal in five (13%), showed arterial insufficiency in five (13%), venous occlusive disease in 26 (65%) and mixed vascular in four (10%). There was an improved SHIM-5 score in 28 (70%) patients, as shown by their haemodynamic values, duration of erection and EHS with therapy, and 66% satisfaction with treatment. Adverse effects (penile pain, headache, facial flushing, dyspepsia, nasal congestion, dizziness) were reported in 17 patients (43%). Conclusion: Chronic use of trimix plus daily low-dose sildenafil improved penile haemodynamics in these patients with ED not responding to on-demand phosphodiesterase-5 inhibitors or ICI with PGE1 monotherapy. [Copyright &y& Elsevier]

Background: Sildenafil and tadalafil are recommended firstline treatments for erectile dysfunction (ED). Sildenafil was legally reclassified to a 'pharmacy' medicine in the UK in 2018., Aim: To assess the prescribing patterns and costs associated with prescribing of ED drugs in England, and to investigate the link between prescribing and deprivation, regional demography, and legal reclassification., Design & Setting: Analyses were conducted of publicly available government data from various sources pertaining to primary care prescribing and demographics in England., Method: Prescribing and cost data from January 2009 to November 2019 were extracted and adjusted for inflation, male populations, and regional deprivation., Results: Between 2009 and 2019 the rate of prescribing, measured as the number of items per 1000 men, increased by 110%. In 2019, the rate of prescribing of ED medicines in the most deprived areas was 21.0% higher than the rate observed in least deprived areas. The northern regions of England approximately had a 50% higher rate of prescribing compared with London. A 1.3% annual increase in the number of prescription items was observed between 2018 and 2019 for Sildenafil, with a 5.8% increase observed from 2017-2018., Conclusion: The two-fold increase in the rate of primary care prescriptions in the past 10 years suggests that more men are being screened for, or seeking help for, ED. The higher rate of prescribing offers opportunity for monitoring of linked risk factors, such as diabetes mellitus, dyslipidaemia, and vascular disorders, in deprived populations. Reclassification of sildenafil had a modest impact on prescribing practices., (Copyright © 2020, The Authors.)

Introduction: Erectile function is an important aspect in the quality of life of many men. For men with erectile dysfunction (ED), a spectrum of treatment options exists. Novel therapies for ED are currently being developed in order to delay surgical placement of a penile prosthesis - the final step in the management of treatment-refractory ED. Areas covered: This review examines innovative treatments such as alternative vasoactive agents, trophic factors and bio-compounds as well as gene and stem cell therapy. All therapies are currently in some phase of development for the management of ED. Using the MedLine and FDA Clinical Trials Registry, recent developments in treatment of ED were queried. Expert opinion: Recent studies have demonstrated the potential for multiple, novel therapies in the treatment of ED. Much of the work requires further experimentation in large-scale, blinded, placebo-controlled studies. This will require a concerted effort to bring these products to market.