The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction

Goldstein, Irwin; Burnett, Arthur L.; Rosen, Raymond C.; Park, Peter W.; Stecher, Vera J.

doi:10.1016/j.sxmr.2018.06.005

Cited by 134 publications

(105 citation statements)

References 59 publications

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“…The efficacy and tolerability of both short- and long-acting PDE5Is are well established 11 ; however, most men still plan for sexual intercourse several hours in advance. 16 This international, real-world survey was conducted to investigate the reasons behind these planning behaviors in men taking short- or long-acting PDE5Is.…”

Section: Discussionmentioning

confidence: 99%

Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries

et al. 2020

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Introduction The effect of erectile dysfunction (ED) on sexual planning behaviors and outcomes in men taking phosphodiesterase type 5 inhibitors (PDE5Is) is not well studied. Aims To assess sexual habits, behaviors, and treatment-related outcomes of PDE5I-treated men with ED. Methods This cross-sectional observational study recruited men aged 30 to 70 years with mild-to-severe ED from 8 diverse countries (the United States, the United Kingdom, Italy, Russia, Turkey, Israel, China, and Japan) to complete an approximately 15-minute survey. Differences were evaluated using bivariate analyses, and data were summarized using descriptive statistics. Main Outcome Measures Self-reported data were collected for demographics, health characteristics, treatment, sexual habits, ED severity, ED-specific quality of life, and treatment satisfaction. Results The survey was completed by 1,575 men. Mean frequency of sexual intercourse was 5.7 times/month. Overall, 87.1% of men always, often, or sometimes planned for sexual activity. Of those planning in advance, 32.8% and 40.6% agreed or strongly agreed that they plan for specific days of the week and times of day, respectively. Sexual planning habits were similar for patients taking short-acting vs long-acting PDE5Is. The most commonly cited reasons for planning sexual activity were needing time to take medication (48.4%), needing to make sure medication has taken effect (43.4%), convenient time for sexual activity (34.9%), and needing the partner’s agreement (33.4%). Mean Self-Esteem and Relationship Questionnaire total score was 56.4. Conclusions The differences in ED burden and sexual planning behavior observed across countries were not influenced by the type of PDE5I being taken, suggesting that cultural differences are an important factor when considering types of ED treatment. These findings provide a better understanding of burden, sexual habits, planning behaviors, quality of life, and treatment-related outcomes among PDE5I-treated men with ED in 8 Western and non-Western countries and may aid healthcare providers in selecting optimal treatments. Goldstein I, Giraldi A, Maculaitis MC, Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries. J Sex Med 2020;8:338–349.

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Section: Discussionmentioning

confidence: 99%

Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries

et al. 2020

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“…However, a growing body of evidence has also proven their usefulness as therapeutic agents in different conditions due to their anti-inflammatory and antioxidant actions, as reported in diabetes [93], hypertension and chronic kidney disease [94]. Sildenafil, the first PDE-5 inhibitor approved for the treatment of ED following its serendipitous discovery [95], has also been investigated as a treatment for COVID-19 patients; indeed, Sildenafil improves pulmonary hemodynamics, as shown in idiopathic pulmonary fibrosis [96], by reducing vascular resistance and remodeling in the pulmonary circulation [97]. Additionally, by inhibiting neointimal formation and platelet aggregation, sildenafil also might prove beneficial in regard to the risk of vascular injury and thrombotic complications in COVID-19 patients [98].…”

Section: Phosphodiesterase-5 Inhibitors In Covid-19mentioning

confidence: 99%

Addressing male sexual and reproductive health in the wake of COVID-19 outbreak

Sansone

Mollaioli

Ciocca

et al. 2020

J Endocrinol Invest

137

147

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Purpose The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a "cytokine storm", which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. Methods A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. Results Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. Conclusion COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.

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“…Sildenafil (also known as Viagra) inhibits PDE5, thereby raising cytoplasmic cGMP levels. Discovered in the late 1980s by Pfizer, sildenafil is used clinically to treat erectile dysfunction and pulmonary arterial hypertension [329,330]. In preclinical rodent models of AD,sildenafil has been shown to rescue memory [177][178][179][180][331][332][333][334][335], decrease A␤ levels [178,179,[333][334][335][336] and tau hyperphosphorylation [177,178,180,331], inhibit GSK3␤ [177][178][179][180] and JNK [331], decrease IL-1␤, IL-6, and TNF-␣ secretion [335], upregulate pSer133-CREB [180,333,335], BDNF [180,336], Arc [180], and Bcl2 [336], downregulate BACE1 [179], A␤PP, caspase-3, and Bax [336], and decrease double-stranded DNA breaks and apoptotic cells [336].…”

Section: Sildenafilmentioning

confidence: 99%

Phosphodiesterase Inhibitors for Alzheimer’s Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale

Sanders

Rajagopal²

2020

Journal of Alzheimer's Disease Reports

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Background: Preclinical studies, clinical trials, and reviews suggest increasing 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) with phosphodiesterase inhibitors is disease-modifying in Alzheimer's disease (AD). cAMP/protein kinase A (PKA) and cGMP/protein kinase G (PKG) signaling are disrupted in AD. cAMP/PKA and cGMP/PKG activate cAMP response element binding protein (CREB). CREB binds mitochondrial and nuclear DNA, inducing synaptogenesis, memory, and neuronal survival gene (e.g., brain-derived neurotrophic factor) and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC1␣). cAMP/PKA and cGMP/PKG activate Sirtuin-1, which activates PGC1␣. PGC1␣ induces mitochondrial biogenesis and antioxidant genes (e.g.,Nrf2) and represses BACE1. cAMP and cGMP inhibit BACE1-inducing NFκB and tau-phosphorylating GSK3␤. Objective and Methods: We review efficacy-testing clinical trials, epidemiology, and meta-analyses to critically investigate whether phosphodiesteraseinhibitors prevent or treat AD. Results: Caffeine and cilostazol may lower AD risk. Denbufylline and sildenafil clinical trials are promising but preliminary and inconclusive. PF-04447943 and BI 409,306 are ineffective. Vinpocetine, cilostazol, and nicergoline trials are mixed. Deprenyl/selegiline trials show only short-term benefits. Broad-spectrum phosphodiesterase inhibitor propentofylline has been shown in five phase III trials to improve cognition, dementia severity, activities of daily living, and global assessment in mild-to-moderate AD patients on multiple scales, including the ADAS-Cogand the CIBIC-Plus in an 18-month phase III clinical trial. However, two books claimed based on a MedScape article an 18-month phase III trial failed, so propentofylline was discontinued. Now, propentofylline is used to treat canine cognitive dysfunction, which, like AD, involves age-associated wild-type A␤ deposition. Conclusion: Phosphodiesterase inhibitors may prevent and treat AD.

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The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction

Cited by 134 publications

References 59 publications

Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries

Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries

Addressing male sexual and reproductive health in the wake of COVID-19 outbreak

Phosphodiesterase Inhibitors for Alzheimer’s Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale

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