Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

BACKGROUND: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Sildenafil Vs. Tadalafil for The Treatment of Benign Prostatic Hyperplasia: A Single-arm Self-controlled Clinical Trial.

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 IPSS- 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 responsiveness 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 (ß = 0.31) compared to tadalafil (ß = 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.

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.

Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails.

INTRODUCTION: On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. AIM: To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. METHODS: PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. MAIN OUTCOME MEASURES: The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). RESULTS: Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. CONCLUSION: For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, et al. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.

A Case of Hepatotoxicity Induced by Adulterated "Tiger King", a Chinese Herbal Medicine Containing Sildenafil.

Detection of Phosphodiesterase Type 5 (PDE-5) inhibitors and their analogues in "100% natural" or "herbal" supplements have been described in numerous reports. However, few reports have been published in relation to actual harm caused by counterfeit erectile dysfunction herbal supplements. We describe a case of a 65-year old male admitted to a tertiary hospital with acute liver toxicity, possibly induced by adulterated "Chinese herbal" supplement "Tiger King" for sexual enhancement. Chemical analysis of the tablets discovered the presence of therapeutic doses of sildenafil with no other herbal components. Other medications were excluded as potential causes of the hepatic impairment. According to the Naranjo adverse drug reaction scale and the Roussel Uclaf Causality Assessment Method (RUCAM) the probability of association of Hepatotoxicity with Sildenafil was "possible" and "probable" respectively (Naranjo score of 4, RUCAM score of 7). Within three days of admission, the patient's clinical status and liver function improved without any specific treatment. His liver function tests normalized 30 days post discharge. Further pharmacovigilance actions should be taken by regulatory authorities and pharmaceutical companies in order to determine the relation between sildenafil and hepatotoxicity. This case emphasizes the importance of raising public awareness on the potential dangers of "Tiger king" in particular, and other counterfeit medications or herbal supplements of unknown origin.

[Falsified dietary food supplements for men: expertise difficulties and medical problems].

Falsified dietary food supplements for men: expertise difficulties and medical problems. According to numerous chemical-toxicological and forensic researches it have been sildenafil and tadalafil in a variety of dietary food supplements. Falsified dietary food supplements, are essentially a substitute for drugs - phosphodiesterase type 5 inhibitor, but are produced with unknown composition and in unknown dose of synthetic pharmaceutical substances. This can cause consumers unpredictable nezative conseauences. including death.

[Pharmacological treatment of benign prostatic hyperplasia]. / Medikamentöse Therapie des benignen Prostatasyndroms.

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.

Use of phosphodiesterase type 5 inhibitors in assistive living and home care settings.

UNLABELLED: The purpose of this descriptive study was to assess frequency of phosphodiesterase type (PDE-5) inhibitor use (sildenafil, tadalafil, ardenafil) in community settings. METHODS: A retrospective record review was conducted to determine PDE-5 inhibitor use in older males (mean age 79.2) residing in three assisted living communities (n=126), or living in private homes with home care services (n=109). RESULTS: Two participants from assisted living had PDE-5 inhibitors listed on medication profiles, while no participants from the home care setting had any listed. IMPLICATIONS: Many factors may have contributed to the absence of PDE-5 inhibitors in records, including comorbidities precluding use; fear of side effects; reluctance to report use; and lack of erectile dysfunction diagnosis to name a few. It is unknown whether sexual function, or the need for PDE-5 inhibitors was ever assessed by providers. Future research is warranted given the aging population and the benefits of holistic assessments.

PDE-5 inhibitors: clinical points.

Erectile dysfunction is usually of vascular origin and is frequently encountered in men with cardiovascular disease. The introduction of phosphodiesterase-5 inhibitors has revolutionized the management of patients with erectile dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring sexual therapy according to patient characteristics and needs. Phosphodiesterase-5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic effects, which need to be taken into account when other cardiovascular drugs are co-administered. Special caution is needed with alpha-blockers, while the co-administration with nitrates is contra-indicated due to the risk of life-threatening hypotension. This review presents the advent of sexual therapy, describes the mechanism of action and the specific characteristics of commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy and safety of these drugs with special emphasis on the cardiovascular system, and discusses the clinical criteria used for the selection of each drug for the individual patient.

Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction.

INTRODUCTION: Several cases of adulteration of dietary supplements with tadalafil, sildenafil, and vardenafil, or their unapproved analogues have been reported worldwide. Mainly, the presence of the latter represents a serious health risk to consumers as their efficacy and toxic effects have not been assessed and may result in unpredictable adverse effects. AIM: To investigate the suspected adulteration with synthetic phosphodiesterase type 5 (PDE-5) inhibitors in a dietary supplement marketed in Argentina for the treatment of erectile dysfunction (ED). METHODS: The content of the capsules of the dietary supplement (sample A) was analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) diode-array detection. From the organic extract of sample A, a major compound was purified by column chromatography (CC). The isolated compound was identified by proton nuclear magnetic resonance (1H NMR) and carbon NMR (13C NMR), heteronuclear single quantum coherence, distortionless enhancement by polarization transfer (DEPT 135), electrospray ionization mass spectrometry, and ultraviolet, and infrared (Fourier transform infrared spectroscopy) spectroscopy. MAIN OUTCOME MEASURE: Proof of adulteration of herbal products with synthetic PDE-5 inhibitors. RESULTS: By TLC and HPLC analysis, a major compound was detected in sample A organic extract. The purification of this extract by CC led to the isolation of a pure compound which was identified according to its spectral data as (6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino [1',2':1,6] pyrido [3,4-b] indole-1,4-dione or aminotadalafil. CONCLUSIONS: An unapproved PDE-5 inhibitor analogue, which was identified as aminotadalafil, has been detected in a dietary supplement. This study represents the first report in Latin America and one of the few independent studies of an adulteration with an unapproved PDE-5 inhibitor of an herbal product for ED treatment.

Which is first? The controversial issue of precedence in the treatment of male sexual dysfunctions.

INTRODUCTION: In male sexual dysfunction (MSD), the presence of sexual comorbidities is relatively frequent. However, what is still a matter of controversy is what the first-line therapy in these patients should be. METHODS: Three scientists and the editor of the Controversies section, all experts in the medical treatment of MSD, present different perspectives on the use of phosphodiesterase type 5 inhibitors (PDE5), testosterone and dapoxetine in erectile dysfunction (ED), hypogonadism, and premature ejaculation (PE). The psychological aspects are discussed by an outstanding expert in psychosexology. MAIN OUTCOME MEASURE: Expert opinion supported by the critical review of the currently available literature. RESULTS: Testosterone should be used before PDE5s in hypogonadal men with comorbid ED; PDE5s should be used before dapoxetine in PE patients with comorbid ED, and counseling should be offered to all subjects with MSD. CONCLUSIONS: Although the answer to the question "which should be first?" is controversial in almost all MSDs, intuition, experience, and evidence should guide the choice of which treatment should be used first. This decision is highly critical in influencing the therapeutic outcome as well the patient's and couple's adherence to treatment.

[Efficiency of initiation with ambrisentan versus bosentan in the treatment of pulmonary arterial hypertension]. / Eficiencia del inicio con ambrisentan frente a bosentan en el tratamiento de la hipertensión arterial pulmonar.

OBJECTIVE: To evaluate the efficiency of initiation with endothelin receptor antagonists, ambrisentan or bosentan, followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids in the treatment of pulmonary arterial hypertension, from the Spanish National Health System perspective. METHODS: A Markov model was developed based on the four New York Heart Association functional classes. A panel of three experts reached a consensus on patient management based on clinical practice. Patients revised their treatment every 12 weeks, based on their health status and previous medication records. Pharmacological treatment costs and costs associated with very frequent adverse events (AE) were considered in a horizon of 60 weeks. Outcomes were measured in qualityadjusted life years (QALY). A probabilistic sensitivity analysis was performed. RESULTS: No clinically relevant differences in QALY per-patient and year were found for initiation with ambrisentan and bosentan: 0.6853 and 0.6902, respectively. Initiation with ambrisentan resulted in lower pharmacological treatment and AE management costs: ?35,550 and ?117 versus ?40,224 and ?171. In the sensitivity analysis, initiation with ambrisentan resulted in a negative significant cost difference: ?-4,982; CI95%[?- 8,014; ?-2,500]; while no significant differences in QALY were found: -0.0044; CI95%[-0.0189; 0.0101]. CONCLUSIONS: Initiation with ambrisentan followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids yields comparable outcomes at lower costs than initiation with bosentan.

Objetivo: Se pretende evaluar la eficiencia del tratamiento secuencial de combinación de la hipertensión arterial pulmonar iniciado con antagonistas del receptor de la endotelina, ambrisentan o bosentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, desde la perspectiva del Sistema Nacional de Salud. Métodos: Se desarrolló un modelo de Markov basado en las cuatro clases funcionales de la New York Heart Association. Un panel de tres expertos alcanzó un consenso sobre el manejo del paciente basado en la práctica clínica. Los pacientes revisaron su tratamiento cada 12 semanas, en función de su estado de salud y de la medicación recibida previamente. Se incluyeron costes farmacológicos y costes asociados al manejo de eventos adversos (EA) muy frecuentes, en un horizonte de 60 semanas. Los resultados se expresaron en términos de los años de vida ajustados por calidad (AVAC). Se realizó un análisis de sensibilidad probabilístico. Resultados: No se encontraron diferencias clínicamente relevantes en los AVAC por paciente y año para el inicio con ambrisentan y bosentan: 0,6853 y 0,6902, respectivamente. El inicio con ambrisentan resultó en un coste farmacológico y asociado al manejo de EA menor: 35.550 ??y 117 ??frente a 40.224 ??y 171 ?. En el análisis de sensibilidad, el inicio con ambrisentan presentó una diferencia de costes totales negativa y significativa: -4.982 ?; IC95%[-8.014 ?; -2.500 ?]; mientras que no se detectaron diferencias significativas en los AVAC: -0,0044; IC95%[-0,0189; 0,0101]. Conclusiones: El tratamiento secuencial de combinación de la HAP iniciado con ambrisentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, proporciona resultados en salud comparables y menores costes que el tratamiento iniciado con bosentan.

The effects of cyclic guanylate cyclase stimulation on right ventricular hypertrophy and failure alone and in combination with phosphodiesterase-5 inhibition.

BACKGROUND: We investigated if soluble guanylate cyclase stimulation either alone or in combination with phosphodiesterase-5 (PDE5) inhibition could prevent pressure overload-induced right ventricular (RV) hypertrophy and failure. METHODS: The soluble guanylate cyclase stimulator BAY 41-2272 (BAY, 10 mg · kg⁻¹ · d⁻¹) either alone or in combination (BAY + SIL) with a PDE5 inhibitor sildenafil (SIL, 100 mg · kg⁻¹ · d⁻¹) was examined for prevention of RV hypertrophy and failure in Wistar rats (n = 73) operated by pulmonary trunk banding. RESULTS: All treatments failed to inhibit the development of RV hypertrophy and failure. In the BAY and BAY + SIL groups, there was an increased mortality. Mean arterial blood pressure was lowered and cardiac output increased in the BAY + SIL group. Systolic RV pressure was increased in the BAY and BAY + SIL groups possibly because of an inotropic response and/or increased venous return. CONCLUSIONS: Stimulation of soluble guanylate cyclase by BAY 41-2272 alone or in combination with sildenafil failed to prevent the development of RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.

Avanafil for the treatment of erectile dysfunction.

Erectile dysfunction is a prevalent condition afflicting millions of men worldwide and can have disastrous effects on a couple's quality of life. With the understanding of the physiology of erections and the discovery of cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5) inhibitors, therapy for erectile dysfunction was revolutionized, and this class of medication became the first-line treatment option for this widespread condition. Despite the ease of use, efficacy and tolerability of the available PDE5 inhibitors, many men discontinue their use, usually related to lack of efficacy or development of adverse events. As such, research into the development of other medications within this drug class is extensive. Avanafil is a novel PDE5 inhibitor with favorable pharmacokinetic and pharmacodynamic profiles with good tolerability and limited adverse events. It was recently approved and launched in Korea, and is currently under review by the U.S. Food and Drug Administration. Its efficacy and purported role in the treatment for erectile dysfunction are reviewed here.

The Global Online Sexuality Survey (GOSS): erectile dysfunction among Arabic-speaking internet users in the Middle East.

INTRODUCTION: Epidemiologic studies exploring sexuality across different cultures and geographic regions are scanty, particularly from the Middle East. The Global Online Sexuality Survey (GOSS) is an Internet-based survey investigating male and female sexual function. GOSS-Arabic-Males is the Arabic version targeting males in the Middle East, exploring prevalence rate of and factors affecting erectile dysfunction and its therapeutic trends, as well as premature ejaculation, attitudes toward genital size, and contraception. AIM: To explore epidemiologic aspects of male sexuality through an online survey. MAIN OUTCOME MEASURES: Prevalence rate of erectile dysfunction, its relationship to risk factors, and therapeutic trends. METHODS: The online survey was randomly offered to Web surfers in the Middle East. RESULTS: Eight hundred four subjects completed the survey. The overall prevalence of ED was 45.1%, strongly correlating with various risk factors studied, including age, diabetes, hypertension under treatment, depression, concerns over genital size, interpersonal distress, premature ejaculation, low libido, and subjective reports of penile deviation. Adjusted to the World Standard Population, the prevalence rate for ED was 47%. Phosphodiesterase (PDE) inhibitors gave a poor response among those with low libido and interpersonal distress, emphasizing the need for proper diagnosis and psychological counseling parallel to medical treatment. Furthermore, PDE inhibitors were stigmatized with unrealistic concerns that decreased their utility to a great extent. CONCLUSION: In the study population of Arab-speaking Internet users, prevalence of erectile dysfunction and effect of risk factors have proven similar to reports from different parts of the world, though not unanimously. Premature ejaculation, low desire, concerns over penile size, and penile curvature are factors to be considered in the evaluation of ED patients. PDE inhibitors are stigmatized with false beliefs that should be addressed through mass media and counseling if this population is to take full benefit from this therapeutic option.