Side effects of sildenafil are similar to those from taking niacin or any vasodilator, namely, headaches, lightheadedness, dizziness, and flushing. Some individuals experience a bluish tinge of their cornea, which makes them feel as if they are wearing light blue–tinted sunglasses. This effect can last for several hours. Syncope and myocardial infarction, the most serious side effects, are seen in men who are also taking nitrates for coronary heart disease. Sildenafil also has adverse effects in people with hypertrophic cardiomyopathy because a decrease in preload and after load in the cardiac output can increase the outflow obstruction, culminating in an unstable hemodynamic state.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (24) | Google ScholarSee all References Erectile function relies on the arterial blood supply from the internal pudendal arteries, which are branches of the hypogastric arterial system (Figure 1). Substantial increases in internal pudendal arterial flow result in pressures within the penis that are comparable to systemic arterial levels.12x12Rampin, O and Giuliano, F. Central control of the cardiovascular and erection systems: possible mechanisms and interactions. Am J Cardiol. 2000; 86: 19F–22F
Yohimbine is an indole alkaloid derived from the bark of the African yohimbe tree (33). Yohimbine has been noted to treat fatigue, depression, diabetes, and sexual dysfunction. A meta-analysis of seven placebo-controlled trials (34) deemed yohimbine superior to placebo for the treatment of ED with rare adverse events. The proposed mechanism of action (35) is via the inhibition of central alpha-2-adrenergic receptors, decreasing central inhibition of arousal, and increasing penile nerve stimulation resulting in increased NO. Common side effects include headache, sweating, agitation, hypertension and insomnia. Contraindications include patients on tricyclic antidepressants, anti-hypertensives and central nervous system stimulants.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil has a 4000-fold increased selectivity for PDE-5 over PDE-3, has negligible effects on heart rate, and has only a modest effect on blood pressure level in healthy persons, with an average systolic pressure decrease of 10 mm Hg with a single dose of 100 mg.3x3Zusman, RM, Morales, A, Glasser, DB, and Osterloh, IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83: 35C–44C
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References During this period, 130 deaths were reported to the US FDA; 41 of these men died or had cardiac arrest within 4 to 5 hours after taking sildenafil, and 27 died or had cardiac arrest either during or immediately after sexual activity. The average age of these men was 64 years. Of the 77 men in this group who died of documented cardiovascular-related events, 41 died of definite or suspected myocardial infarction, 27 died after cardiac arrest, and 6 had symptoms of cardiac disease at the time of death. Sixteen of the men had taken nitroglycerin or organic nitrates in association with sildenafil; another 3 had nitroglycerin in their possession at the time of death. In 48 men, the cause of death was unknown, and another 3 died of cerebrovascular accidents. Overall, it was concluded that sildenafil was not associated with an excess of cardiovascular death.
While Western medicine emphases the link between cardiovascular function and ED, TCM places importance on liver and kidney ailments as causative factor for development of ED. Western medicine involves a step-wise approach by targeting the relevant organ systems to treat various clinical symptoms; but TCM focuses on restoring the balance between various organs to achieve harmony and holistic approach to inner sense (4). The following article reviews our current understanding regarding the philosophical approach, and evaluates the evidence surrounding various ED therapies between mainstream Western medicine and TCM (see Table 1).
A follow-up study from the ExCEED database compared men with ED and prostate cancer to men with ED without prostate cancer and found that the prostate cancer survivors had worse erectile function but reported better quality of life than those without prostate cancer.37 The authors hypothesized that the prostate cancer survivors were able to “rationalize” away their sexual dysfunction with the knowledge that they may have been “cured” of their prostate cancer. Clearly, diabetic men could not use the same rationale.
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Erectile dysfunction carries an independent risk for cardiovascular events. A considerable number of studies have examined the ability of ED to predict the risk of future fatal and non-fatal cardiovascular events (myocardial infarction, stroke, revascularization) and total mortality in the general population and in high CV risk patients, in diabetics and in heart failure patients.5,19–22 In a meta-analysis of 14 prospective cohort studies involving 92 757 men followed for a mean period of 6.1 years (Figure 4), ED increased significantly and independently of traditional risk factors the risk of CV events, CV mortality, myocardial infarction, cerebrovascular events, and all-cause mortality by 44, 19, 62, 39, and 25% respectively.5 This predictive ability also extends in men with known CVD: ED increased the risk of all-cause mortality by 90%.5 Of importance, the predictive ability of ED is higher in younger ED patients5 despite the fact that probability of ED increases with age, most likely identifying a group of patients with early and aggressive vascular disease.23 Clinical implementation of ED as a biomarker relies on whether its addition on classical risk scores such as the Systematic COronary Risk Evaluation (SCORE) or the Framingham correctly reclassifies a meaningful percentage of patients into a higher or lower risk category. To this end, data are limited. Yet, in a population-based study of men 40–70 years of age, the addition of the ED status to the Framingham risk score resulted in a reclassification of 6.4% of low-risk patients to intermediate risk.19

When antihypertensive medication comes to the fore, certain issues need to be carefully addressed. This is due to the fact that medically induced erectile dysfunction is one of the major reasons for non-adherence and treatment discontinuation, a reality that could have deleterious consequences on patient’s cardiovascular profile and health quality in the long term[38,39].
Acupuncture. Though acupuncture has been used to treat male sexual problems for centuries, the scientific evidence to support its use for erectile dysfunction is equivocal at best. In 2009, South Korean scientists conducted a systematic review of studies on acupuncture for ED. They found major design flaws in all of the studies, concluding that "the evidence is insufficient to suggest that acupuncture is an effective intervention for treating ED."
Perk J,  De Backer G,  Gohlke H,  Graham I,  Reiner Z,  Verschuren WM,  Albus C,  Benlian P,  Boysen G,  Cifkova R,  Deaton C,  Ebrahim S,  Fisher M,  Germano G,  Hobbs R,  Hoes A,  Karadeniz S,  Mezzani A,  Prescott E,  Ryden L,  Scherer M,  Syvänne M,  Scholte Op Reimer WJ,  Vrints C,  Wood D,  Zamorano JL,  Zannad F. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR), Eur Heart J , 2012, vol. 33 (pg. 1635-1701)https://doi.org/10.1093/eurheartj/ehs092
Erection is a neurovascular event that involves spinal and supra spinal pathways. The final common pathway involves the release of nitric oxide (NO) from both endothelial cells and neurons, which acts as a vasodilator causing penile engorgement and erection. NO is degraded by the enzyme phosphodiesterase (PDE) type 5 in the penis. Erectile dysfunction (ED), defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance, results when the neurovascular pathway is interrupted by medical conditions or drugs. A 15-item self-administered questionnaire, the International Index of Erectile Function (IIEF), is one of the most useful tools to evaluate erectile function (EF) in clinical trials, although of much less use in routine clinical practice. The MMAS (Massachusetts Male Aging Study) was the first major epidemiological investigation to study the prevalence of ED. The study found that ED was three times more common in patients with diabetes mellitus. The aetiopathogenesis of ED in diabetes is multifactorial, with vascular and neural factors being equally implicated. Hyperglycaemia is believed to give rise to biochemical perturbations that lead to these microvascular changes. In the MMAS, ED in diabetes was strongly correlated with glycaemic control, duration of disease and diabetic complications. The incidence increased with increasing age, duration of diabetes and deteriorating metabolic control, and was higher in individuals with type 2 diabetes than those with type 1.ED in men with diabetes often affects their quality of life and, as patients are often reluctant to come forward with their symptoms, a carefully taken history is one of the most useful approaches in identifying affected individuals. The PDE inhibitors have revolutionised the management of ED and oral drug therapy is currently first-line therapy for the condition. These agents act by potentiating the action of intracavernosal NO, thereby leading to a more sustained erection. Sildenafil was the first PDE5 inhibitor to undergo evaluation and has been studied extensively. More recently two other agents, vardenafil and tadalafil, have been introduced. All the drugs have been shown to be effective across a wide range of aetiologies of ED, including diabetes. The drugs have been shown to improve EF domain scores, penetration and maintenance of erection, resulting in more successful intercourse. Their effects are greater at higher doses. Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity. Common adverse effects include headache, nasal congestion and dyspepsia, all actions related to inhibition of PDE5. The drugs are generally well tolerated and withdrawal from the clinical studies as a result of drug-related adverse effects were rare. The use of PDE5 inhibitors in the presence of oral nitrates is absolutely contraindicated. The clinical studies to date have not evaluated the use of one drug in the case of treatment failure with another agent. Sublingual apomorphine, which stimulates central neurogenic pathways, is a new agent and may be a suitable alternative in those patients in whom PDE5 inhibitors are ineffective or contraindicated. In clinical trials, all IIEF domains except sexual desire were found to have improved after apomorphine. The median times to erection in these studies were 18.9 and 18.8 minutes for the 2 and 3mg doses, respectively. Intraurethral and intracavernosal alprostadil may be a useful alternative when oral drug therapy is ineffective or contraindicated. The management of ED in the diabetic patient may often involve a multidisciplinary approach where psychosexual counselling and specialist urologist advice is required in addition to the skills and expertise of the diabetologist. Finally, the introduction of the new oral agents have completely revolutionised the management of ED and allowed more individuals to come forward for treatment.
Diabetes mellitus (DM) is strongly associated with an increased risk of erectile dysfunction (ED), the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance, but this condition can be successfully treated in the majority of diabetes patients. ED is present in 32% of type 1 and 46% of type 2 DM patients. Several population- based studies of ED prevalence calculated the odds ratios for the association between ED and various chronic diseases. An odds ratio must be sufficiently greater than 1.0 to identify an increased risk. Diabetes has an odds ratio, ED risk multiplier of 4.1, compared with 1.7 for hyperlipidemia and 1.6 for hypertension. Erectile dysfunction in diabetes mellitus (EDDM) patients has been considered to have an organic etiology. Healthcare providers have long realized that ED can be the first symptom of DM.
Gutiérrez-González, Enrique; Castelló, Adela; Fernández-Navarro, Pablo; Castaño-Vinyals, Gemma; Llorca, Javier; Salas-Trejo, Dolores; Salcedo-Bellido, Inmaculada; Aragonés, Nuria; Fernández-Tardón, Guillermo; Alguacil, Juan; Gracia-Lavedan, Esther; García-Esquinas, Esther; Gómez-Acebo, Inés; Amiano, Pilar; Romaguera, Dora; Kogevinas, Manolis; Pollán, Marina; Pérez-Gómez, Beatriz. “Dietary Zinc and Risk of Prostate Cancer in Spain: MCC-Spain Study.” Nutrients. Jan 2019, 11(1).

Crossref | PubMed | Scopus (23) | Google ScholarSee all References Similar to sildenafil, vardenafil produces a slight hypotensive effect with an average maximal decrease in blood pressure level of 5 to 10 mm Hg.74x74Gresser, U and Gleiter, CH. Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil—review of the literature. Eur J Med Res. 2002; 7: 435–446
PubMed | Google ScholarSee all References As with sildenafil, use of nitrate or NO-donor medications is contraindicated while taking tadalafil because of the potential for marked hypotensive interactions.74x74Gresser, U and Gleiter, CH. Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil—review of the literature. Eur J Med Res. 2002; 7: 435–446
Before a man concludes that oral drugs don’t work for him, he should have his testosterone levels checked to rule out hormone deficiency as the cause of (or as a contributor to) his sexual dysfunction. Other symptoms of low testosterone include a low sex drive and infertility. Checking testosterone levels requires a blood test. If a man’s levels of testosterone are decreased or at the lower end of normal, his doctor may prescribe supplemental testosterone therapy, either as testosterone injections or testosterone gel, which is applied daily to the skin. In some cases, testosterone therapy alone can resolve sexual dysfunction, or it can be combined with the use of oral erectile dysfunction drugs.
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