madman
Super Moderator
Efficacy of Aspirin for Vasculogenic Erectile Dysfunction in Men: A MetaAnalysis of Randomized Control Trials
Muhammad Irfan, Shaiful Bahari Ismail, Norhayati Mohd Noor, and Nik Hazlina Nik Hussain
Abstract
One of the major causes of erectile dysfunction (ED) is an endothelial vascular disorder. This meta-analysis is performed to determine the efficacy of aspirin on erectile function in men with vasculogenic ED. For this purpose, CENTRAL, MEDLINE, and reference lists of articles up to November 2019 were searched. Randomized controlled trials (RCTs) were selected that compared aspirin with placebo in men of any ethnicity with vasculogenic ED. A total of 58 trials were retrieved. Finally, two trials of 214 men fulfilled our selection criteria. High selection and detection bias were identified for one trial. The participants showed a significant improvement in erectile function when they took aspirin (mean difference: 5.14, 95% CI [3.89, 6.40], and I2 = 0%). Although the present meta-analysis suggested that aspirin has a significant effect on the improvement of erectile function, there were limited RCTs available on this topic, and doses of aspirin varied. Additional studies are needed to support findings from this meta-analysis. Aspirin needs to be considered by practitioners when prescribing drugs for vasculogenic ED.
Background Erectile dysfunction (ED), the most common sexual dysfunction in men, is defined as the inability to achieve or maintain an erection adequate for intercourse (Yafi et al., 2016). ED is caused by psychogenic and organic factors. Organic causes explain up to 80% of ED cases. Organic ED encompasses neurogenic, endocrinologic, vasculogenic, and medication or substance-induced factor. Vasculogenic ED is mostly caused by arterial or inflow disorders, rarely by venous outflow disorders, and is the most prevalent among all cases of organic ED (Ende, 1990).
The process of achieving and sustaining an erection is regulated by various molecules released on sexual stimulation. Nitric oxide (NO) released from nerves in the corpora cavernosa is one of these important molecules (Ralph, 2005). NO diffuses into the smooth muscle cells of cavernosa and increases the concentration of cyclic guanosine monophosphate (cGMP) in these cells (Francis et al., 2010). The high levels of cGMP then relax the musculature by decreasing calcium ion concentrations in these smooth muscle cells (Ghalayini, 2004). This whole mechanism increases blood flow and entraps more blood in penile tissues, hence strengthening the hydrostatic skeleton of the penis for an erection (Dean & Lue, 2005). However, the erection is affected by cGMP deactivation due to a cGMP specific phosphodiesterase (PDE) type 5 enzyme expressed abundantly in the cavernosa. Therefore, PDE5 inhibitors are the most widely used and effective group of medicines (e.g., sildenafil, avanafil, tadalafil, vardenafil) for the treatment of ED (Rosen & Kostis, 2003).
The NO pathway has other important functions in the body, such as preventing platelet aggregation, an increase in reactive oxygen species, ischemia, reperfusion injury, hypertension, and heart failure (Ahluwalia et al., 2016; Raddino et al., 2007). Cardiovascular diseases (CVDs) have a strong correlation with reduced NO production in the body, and hence with ED. The onset of ED is considered a sign of the onset of vascular diseases (Mobley et al., 2017). Most conventional medicines (diuretics, adrenergic antagonists, and calcium blockers) for CVD may aggravate ED (Chang et al., 1991; Simonsen, 2002).
Common factors for decreased bioavailability of NO in the body are old age, poor diet (namely, vitamin C deficient and arginine and fat-rich contents), oxidative stress, disease (e.g., sepsis, CVD, and nephropathies), sedentary lifestyle, and side effects from medications (e.g., antidepressants; Luiking et al., 2010; Raddino et al., 2007; Razny et al., 2011; Saroukhani et al., 2013). Conventional medicines and methods used for the treatment of ED are expensive (Tan, 2000), often unavailable in certain conservative countries or need a physician’s prescription, and may not be suitable for CVD patients, who may adversely interact with the treatments they are given (Herschorn, 2003; Simonsen, 2002). Conventional medicines for ED need to be taken before every sexual intercourse to ensure effective concentrations of the drug reach the penile vasculature through circulation (Huang & Lie, 2013). There is a dire need to identify a less expensive, easily available, and effective drug to treat vasculogenic ED.
In this regard, aspirin is a medicine available over the counter, is less expensive, and with negligible, minor, and rare side effects; it also has the potential to treat vasculogenic ED along with CVD (Bayraktar & Albayrak, 2018; Saroukhani et al., 2013; Taubert, 2008). Aspirin increases blood flow in the vessels by not only inhibiting platelet aggregation activity but also by directly stimulating the activity of endothelial NO synthase to increase the production of NO for smooth muscle relaxation (Dzeshka et al., 2016). Previous studies reported an improvement in erectile function in men and animal models when cases of vasculogenic ED were treated with aspirin. The aim of this meta-analysis is to report the effect of aspirin on the improvement of erectile function.
Conclusion
The present meta-analysis was done to include all RCTs that reported the efficacy of aspirin for the treatment of vasculogenic ED in men. The analyses suggested that erectile function is significantly improved by the intervention of aspirin compared to the placebo group. The availability of a few RCTs suggests there is a need for further trials on the efficacy of aspirin for vasculogenic ED in men in comparison to the placebo group in double-blinded RCTs.
Muhammad Irfan, Shaiful Bahari Ismail, Norhayati Mohd Noor, and Nik Hazlina Nik Hussain
Abstract
One of the major causes of erectile dysfunction (ED) is an endothelial vascular disorder. This meta-analysis is performed to determine the efficacy of aspirin on erectile function in men with vasculogenic ED. For this purpose, CENTRAL, MEDLINE, and reference lists of articles up to November 2019 were searched. Randomized controlled trials (RCTs) were selected that compared aspirin with placebo in men of any ethnicity with vasculogenic ED. A total of 58 trials were retrieved. Finally, two trials of 214 men fulfilled our selection criteria. High selection and detection bias were identified for one trial. The participants showed a significant improvement in erectile function when they took aspirin (mean difference: 5.14, 95% CI [3.89, 6.40], and I2 = 0%). Although the present meta-analysis suggested that aspirin has a significant effect on the improvement of erectile function, there were limited RCTs available on this topic, and doses of aspirin varied. Additional studies are needed to support findings from this meta-analysis. Aspirin needs to be considered by practitioners when prescribing drugs for vasculogenic ED.
Background Erectile dysfunction (ED), the most common sexual dysfunction in men, is defined as the inability to achieve or maintain an erection adequate for intercourse (Yafi et al., 2016). ED is caused by psychogenic and organic factors. Organic causes explain up to 80% of ED cases. Organic ED encompasses neurogenic, endocrinologic, vasculogenic, and medication or substance-induced factor. Vasculogenic ED is mostly caused by arterial or inflow disorders, rarely by venous outflow disorders, and is the most prevalent among all cases of organic ED (Ende, 1990).
The process of achieving and sustaining an erection is regulated by various molecules released on sexual stimulation. Nitric oxide (NO) released from nerves in the corpora cavernosa is one of these important molecules (Ralph, 2005). NO diffuses into the smooth muscle cells of cavernosa and increases the concentration of cyclic guanosine monophosphate (cGMP) in these cells (Francis et al., 2010). The high levels of cGMP then relax the musculature by decreasing calcium ion concentrations in these smooth muscle cells (Ghalayini, 2004). This whole mechanism increases blood flow and entraps more blood in penile tissues, hence strengthening the hydrostatic skeleton of the penis for an erection (Dean & Lue, 2005). However, the erection is affected by cGMP deactivation due to a cGMP specific phosphodiesterase (PDE) type 5 enzyme expressed abundantly in the cavernosa. Therefore, PDE5 inhibitors are the most widely used and effective group of medicines (e.g., sildenafil, avanafil, tadalafil, vardenafil) for the treatment of ED (Rosen & Kostis, 2003).
The NO pathway has other important functions in the body, such as preventing platelet aggregation, an increase in reactive oxygen species, ischemia, reperfusion injury, hypertension, and heart failure (Ahluwalia et al., 2016; Raddino et al., 2007). Cardiovascular diseases (CVDs) have a strong correlation with reduced NO production in the body, and hence with ED. The onset of ED is considered a sign of the onset of vascular diseases (Mobley et al., 2017). Most conventional medicines (diuretics, adrenergic antagonists, and calcium blockers) for CVD may aggravate ED (Chang et al., 1991; Simonsen, 2002).
Common factors for decreased bioavailability of NO in the body are old age, poor diet (namely, vitamin C deficient and arginine and fat-rich contents), oxidative stress, disease (e.g., sepsis, CVD, and nephropathies), sedentary lifestyle, and side effects from medications (e.g., antidepressants; Luiking et al., 2010; Raddino et al., 2007; Razny et al., 2011; Saroukhani et al., 2013). Conventional medicines and methods used for the treatment of ED are expensive (Tan, 2000), often unavailable in certain conservative countries or need a physician’s prescription, and may not be suitable for CVD patients, who may adversely interact with the treatments they are given (Herschorn, 2003; Simonsen, 2002). Conventional medicines for ED need to be taken before every sexual intercourse to ensure effective concentrations of the drug reach the penile vasculature through circulation (Huang & Lie, 2013). There is a dire need to identify a less expensive, easily available, and effective drug to treat vasculogenic ED.
In this regard, aspirin is a medicine available over the counter, is less expensive, and with negligible, minor, and rare side effects; it also has the potential to treat vasculogenic ED along with CVD (Bayraktar & Albayrak, 2018; Saroukhani et al., 2013; Taubert, 2008). Aspirin increases blood flow in the vessels by not only inhibiting platelet aggregation activity but also by directly stimulating the activity of endothelial NO synthase to increase the production of NO for smooth muscle relaxation (Dzeshka et al., 2016). Previous studies reported an improvement in erectile function in men and animal models when cases of vasculogenic ED were treated with aspirin. The aim of this meta-analysis is to report the effect of aspirin on the improvement of erectile function.
Conclusion
The present meta-analysis was done to include all RCTs that reported the efficacy of aspirin for the treatment of vasculogenic ED in men. The analyses suggested that erectile function is significantly improved by the intervention of aspirin compared to the placebo group. The availability of a few RCTs suggests there is a need for further trials on the efficacy of aspirin for vasculogenic ED in men in comparison to the placebo group in double-blinded RCTs.
