The initial event for normal erectile function is sexual stimulation. Subsequent to processing in the central nervous system neural impulses are conveyed along the spinal cord, exiting through the pelvic parasympathetic preganglionic nerves. These pelvic nerves form the pelvic plexus and send their message through first messenger, acetyl choline, to the cavernosal nerves. The cavernosal nerves enter erectile bodies (corpora cavernosa) (Figure 1). Here, their nerve endings release a second messenger, nitric oxide. Nitric oxide activates the enzyme guanylyl cyclase, which lyses guanosine triphosphate (GTP) to produce a third messenger, the intracellular cyclic guanosine monophosphate (cGMP). Ultimately, the result is a decrease of intracellular calcium and an opening of potassium channels with the resultant relaxation of vascular smooth muscle in the arteries, aterioles, and sinusoids of the corpora cavernosa. The sinusoids open and rapidly fill with blood. Finally, the distended sinusoids compress their drainage pathways (venules) against the fibroelastic covering of the cavernosal bodies (tunica albuginea) and trap the blood in cavernosal bodies. The combination of an increased inflow of blood into the penis and coincident markedly diminished outflow results in rapidly increasing intracavernosal pressure that ultimately approximates systolic pressure. At this pressure the penis has sufficient axial rigidity to permit vaginal penetration.
The safety of PDE5 inhibitors in patients with IHD has been shown in multiple trials. Arruda-Olson et al. investigated the safety of sildenafil during exercise stress tests in patients with IHD to ascertain whether the drug induces or exacerbates myocardial ischaemia. This was a prospective, randomised crossover study that demonstrated safety of sildenafil when given 1 hour before an exercise stress test.69 Another study that investigated 120 trials of sildenafil revealed that the rates of MI and cardiovascular death with sildenafil are as low as with placebo.70
The medications used to treat high blood pressure do not take into account the symptoms of erectile dysfunction, as their intention is to lower the blood pressure to a more manageable state, reducing the stress put on blood vessels. High blood pressure and ED are seen as separate entities, with the former taking priority for pharmaceutical treatment. This means that the medications used might do nothing to cure erectile dysfunction and may, in fact, prolong it. Medications that lower blood pressure might actually cause a low blood pressure state in the groin area and the arteries supplying the penis, making it near impossible to achieve an erection. The following are examples of such medications:
DHEA. Testosterone is essential for a healthy libido and normal sexual function, and erectile dysfunction sufferers known to have low testosterone improve when placed on prescription testosterone replacement therapy. Similarly, studies have shown that taking over-the-counter supplements containing DHEA, a hormone that the body converts to testosterone and estrogen, can help alleviate some cases of ED. But DHEA can cause problems, including suppression of pituitary function, acne, hair loss and its long-term safety is unknown, says McCullough. For this reason, many experts discourage use of the supplements.

Diabetic damage doesn’t stop with these small vessels, he said. “You really have two parallel situations: You need blood flow that feeds the muscle of the penis, and you need an artery dedicated to bringing blood rapidly when a man becomes aroused and wants to be sexually active,” he said. “That artery is also affected by diabetes. They’ll say ‘I can get a partial erection, but I can’t maintain it.’ ”
Erectile dysfunction is defined as the inability to attain or maintain a penile erection sufficient for satisfactory sexual performance. Cases of ED may be classified as predominantly organic in nature, predominantly psychogenic, or mixed. Usual organic aetiologies are vasculogenic, hormonal, and neurogenic. Owing to the relationship of vasculogenic ED with CVD, it is important to distinguish men with predominantly vasculogenic ED from those with predominantly psychogenic ED or non-vasculogenic organic ED.
ED is a common complication of diabetes and people with diabetes are also prone to developing cardiovascular complications.48 The risk of ED is relatively high in patients with known CVD. This was supported by a study of men with known CVD, in which ED was substantially predictive of all-cause mortality and the composite of CVD death, admission for heart failure, MI and stroke.17 Macroangiopathy, microangiopathy and endothelial dysfunction are among the mechanisms by which diabetes causes ED.

Erne P,  Schoenenberger AW,  Zuber M,  Burckhardt D,  Kiowski W,  Dubach P,  Resink T,  Pfisterer M. Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study, Eur Heart J , 2007, vol. 28 (pg. 2110-2117)https://doi.org/10.1093/eurheartj/ehm273
Testosterone cypionate and testosterone enanthate injections are used for replacement therapy in patients with low testosterone. Other formulations, such as gels and patches, are recommended in older patients with chronic conditions.57 Serum prostate specific antigen should be measured before starting testosterone replacement, then 3–6 months after starting the treatment, followed by annual measurement.74
Ginkgo Biloba is promoted to treat conditions ranging from hypertension to Alzheimer’s dementia. There is evidence that shows improvement of memory enhancements in the geriatric population (47), improvement in terms of cognitive function via effect on cerebral vasculature (48), improvement of claudication distance and cutaneous ulcers in patients with peripheral vascular disease (49). Ginkgo Biloba extract is proposed to induce NO in endothelial cells and thus causing relaxation of vascular smooth muscles. Animal studies have reported relaxation of rabbit corpus cavernosal smooth muscle cells with the use of Ginkgo Biloba (50). Adverse effects include headaches, major bleeding (in patient who are taking warfarin concurrently) and seizures with reported fatality (36).

Abstract | Full Text | Full Text PDF | PubMed | Scopus (46) | Google ScholarSee all References Sedentary patients with a history of cardiac disease and patients with unstable angina or advanced congestive heart failure should undergo a full medical evaluation before resuming sexual activity.80x80Muller, JE. Triggering of cardiac events by sexual activity: findings from a case-crossover analysis. Am J Cardiol. 2000; 86: 14F–18F


Abstract | PubMed | Scopus (136) | Google ScholarSee all References Other candidate mechanisms linking ED and cigarette smoking include hypercoagulability and increased platelet aggregation, increased release of free fatty acids and catecholamines, changes in NO synthetic pathways, and a possible direct toxic effect on vascular endothelium.13x13Chung, WS, Shim, BS, and Park, YY. Hemodynamic insult by vascular risk factors and pharmacologic erection in men with erectile dysfunction: Doppler sonography study. World J Urol. 2000; 18: 427–430
Second-generation cardioselective beta-blockers (atenolol, metoprolol, bisoprolol, etc.) can also lead to ED. Atenolol was shown to cause significant reduction of sexual activity compared with placebo in a double-blind, parallel-arm study.22 The same study also showed a significant reduction in testosterone levels with atenolol versus valsartan. An open, prospective study of hypertensive men treated with atenolol, metoprolol and bisoprolol for at least 6 months showed high prevalence of ED – approaching 66 % – in these patients.23
High blood pressure, otherwise known as hypertension, can contribute to erectile dysfunction (ED). Some of the medications used to treat high blood pressure can cause ED as well. According to the authors of one study, about 30 percent of men with high blood pressure also have had ED. Finding a medication that treats high blood pressure without causing ED is a goal of many men.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Another contraindication is the use of recreational drugs (“poppers”) that contain amyl nitrate. The guidelines also caution use in patients who have a high risk of cardiovascular effects, including patients with active coronary artery disease who are not taking nitrates, patients with congestive heart failure with a borderline low blood pressure level and low blood volume, or those with complicated multidrug antihypertensive regimens.
For patients who failed oral medical therapy or unable to tolerate the side effects, intracavernosal injection of vasoactive agents can often provide effective alternative. Various vasoactive agents such as alprostadil, papaverine or phentolamine have been used either as single agent or combination agents to potentiate the NO release and cavernosal smooth muscle vasodilation. However, intracavernosal injection therapy has high attrition rate and can be associated pain especially with alprostadil injection (2). The practice of isolating compounds and understanding its pharmacological attributes before using it as a drug therapy has been a strength of Western medicine.
One study the authors reviewed measured these changes in middle-aged men with and without coronary artery disease. This study found that the peak heart rate during intercourse was lower than heart rates measured during the patients' normal daily activities. The study participants' peak oxygen consumption levels during intercourse were moderate -- comparable to their oxygen consumption levels during moderate activities such as walking on level ground at 3 to 4 miles per hour, climbing stairs slowly or doing general housework such as vacuuming.
Crossref | PubMed | Scopus (53) | Google ScholarSee all References This study found that, although hypertensive patients had more coronary artery disease, no direct evidence supported an association between hypertension and arteriogenic impotence, as measured by the PBI, peak systolic velocity, and resistive index, in patients with mild to moderate hypertension.
In diabetic patients who fail medical management of ED, penile implantation surgery remains a viable therapeutic option. In a recent review of 372 men who underwent implantation of a three-piece inflatable penile implant, 86% reported that the device was still functional 5 years after implantation, and 79% reported that they used the device at least twice monthly.59
Crossref | PubMed | Scopus (528) | Google ScholarSee all References Sildenafil also has good efficacy in patients with ischemic heart disease, as shown by a retrospective subanalysis of data from 11 double-blind, placebo-controlled studies involving 3672 patients with ED and ischemic heart disease who were not taking nitrates.59x59Kloner, RA. Cardiovascular risk and sildenafil. Am J Cardiol. 2000; 86: 57F–61F
Crossref | PubMed | Google ScholarSee all References Regular exercise can significantly decrease the patient's risk of having a myocardial infarction during sexual intercourse by increasing the patient's functional reserve, decreasing the heart rate, and increasing the stroke volume.8x8Muller, JE, Mittleman, A, Maclure, M, Sherwood, JB, Tofler, GH, and Determinants of Myocardial Infarction Onset Study Investigators. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. JAMA. 1996; 275: 1405–1409
Sexual dysfunction refers to a problem during any phase of the sexual response cycle that prevents the individual or couple from experiencing satisfaction from the sexual activity. The sexual response cycle has four phases: excitement, plateau, orgasm, and resolution. Sexual dysfunction can be caused by physical and emotional factors, or a combination of both. The side effects of some medications also can lead to sexual dysfunction.
Eastern medicine should be fully exploited, and integrated with modern medicine to combine the advantages of both TCM and Western medicine. More research should be conducted into the efficacy and safety of TCM, and integration of TCM and Western medicine may provide promising breakthroughs in future clinical treatment. This strategy may allow for the development of new therapeutic strategies based on concepts of TCM and integrated medicine. There is a need for multimodal therapy and holistic approach to treat men (and their partners) with ED through complementary use of herbal supplements and modern drug to optimize underlying medical comorbidities; acupuncture, exercise or massage to reduce stress and strengthen the body; introduction and escalation of various medical therapy with use of mechanical therapy to further enhance penile erection; and lastly surgical intervention in suboptimal or refractory ED cases.
The prevalence of erectile dysfunction is approximately 2-fold higher in hypertensive patients compared to normotensive individuals. However, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients. Hypertension per se and antihypertensive drug therapy may contribute to the development of erectile dysfunction in patients with arterial hypertension. The management of erectile dysfunction in hypertensive patients is tricky and should take into account the different effects of antihypertensive drug categories on erectile function. Lifestyle modification should be the mainstay of treating erectile dysfunction in patients with untreated hypertension. Switching antihypertensive therapy should be considered in treated hypertensive patients, unless administered drugs are absolutely indicated for the individual patient. Otherwise, PDE-5 inhibitors should be used, since they are both effective and safe in hypertensive patients. Finally, erectile dysfunction offers the opportunity to recognize asymptomatic cardiovascular disease and better characterize the relevant risk with obvious benefits for cardiovascular disease prevention.
The vacuum device is approved by USA Food and Drug Administration (FDA) for treatment of ED since 1982. Vacuum therapy (VT) works by creating a negative pressure environment around the penis through the use of a cylindrical housing attached to a pump mechanism, which can be manually-operated or battery-operated. Vacuum draws mixed arterial and venous blood into the corporal bodies and distends the corporal sinusoids to create an erected penis. If a pre-loaded constriction band is applied over the base of the penis to prevent outflow of blood and maintain tumescence for intercourse, it is considered a vacuum constriction device (VCD). It is recommended that the constriction band be removed within 30 mins to return the penis to its flaccid state, as prolonged application of the constriction band can compromise both arterial and venous blood flow (7). Some minor side effects associated with VCD are penile discomfort, coldness, numbness, bruising and pain on ejaculation. Major side effects such as penile skin necrosis, gangrene, urethral injury and Peyronie’s disease are very rare (8).
Although ED is a common complication of diabetes, its effect on quality of life is not well understood. Recent work for the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database demonstrates that in the general population of patients presenting to their urologist, ED negatively affects both general and disease-specific health-related quality of life (HRQOL).35 While this study provides insight into the detrimental affect of ED on quality of life, the cohort is somewhat selected, in that all of the patients were seen in sexual dysfunction clinics and therefore may have been more likely to be bothered by their condition and to report worse quality of life.
The views expressed in this article intend to highlight alternative studies and induce conversation. They are the views of the author and do not necessarily represent the views of hims, and are for informational purposes only, even if and to the extent that this article features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment, and should never be relied upon for specific medical advice.

Faced with concern about ED pills and the heart, the FDA has urged caution in patients who have suffered heart attacks, strokes, or serious disturbances of the heart's pumping rhythm in the previous six months, in men with a history of congestive heart failure or unstable angina, and in men with low blood pressure or uncontrolled high blood pressure (above 170/110 mm Hg). Because certain medications can boost the blood levels of these drugs, men taking erythromycin or certain antifungal or anti-HIV medications should use only low-dose PDE-5 inhibitors. Reduced dosage is also important for men with advanced age and for those with significant kidney or liver disease.


Patients who use this therapy should be trained under the guidance of a urologist, and sterile technique must be used. The drugs must be injected into the shaft of the penis and into one of the penile erectile bodies (corpus cavernosum) 10–15 min before intercourse. Most patients do not complain of pain upon injection. Sexual stimulation is not required, and resulting erections may last for hours. Side effects include penile pain and priapism. The cost is about $12–20 per injection.


The diagnosis of ED in a patient may affect its management in two ways.30 The first relates to the fact that the ED patient, irrespective of whether he has or has not established CVD, is ‘reclassified’ into a higher risk category for future CV events. Management in this case is altered in the sense that more aggressive treatment of risk factors, as well as a close follow-up, is warranted. Implementation of biomarkers in this setting is desirable.

The use of penile support device such as penile cast worn externally during intercourse has been tried to provide length and rigidity to the penile shaft (24). Each device can be customised to the patient’s penile size and provided an option for patients who are seeking non-pharmaceutical/non-invasive treatment, or have end-organ failure who may not be candidates for, or unable to afford, penile prosthesis implant.

Abstract | Full Text | Full Text PDF | PubMed | Scopus (53) | Google ScholarSee all References Erectile dysfunction is a common physiological disorder. According to estimates from the National Institutes of Health, ED affects 10 million to 20 million men in the United States; another 10 million men are affected by partial ED, defined as present but diminished erectile function.2x2NIH Consensus Development Panel on Impotence. NIH Consensus Conference: impotence. JAMA. 1993; 270: 83–90
SOURCES: American Urological Association, "AUA Guideline on the Management of Erectile Dysfunction: Diagnosis and Treatment Recommendations." Barksdale, J. Pharmacotherapy, May 1999; vol 19: pp 573-581. Ferrario, C. Journal of Clinical Hypertension, November/December 2002; vol 4: pp 424-432. Fogari, R. American Journal of Hypertension, January 2001; vol. 14: pp 27-31. Grimm, R. Hypertension, January 1997; vol 29: pp 8-14. Llisteri, J. American Journal of the Medical Sciences, May 2001; vol. 321: pp 336-341. WebMD Medical Reference provided in collaboration with The Cleveland Clinic: "Hypertension: Treatment With ACE Inhibitors."
• Blood Vessels: Diabetes damages blood vessels, especially the smallest blood vessels such as those in the penis. Diabetes can also cause heart disease and other circulatory problems. Proper blood flow is absolutely crucial to achieving erection. “Erection is a hydraulic phenomenon that occurs involuntarily,” says Arturo Rolla, MD, of Harvard University School of Medicine. “Nobody can will an erection!” Anything that limits or impairs blood flow can interfere with the ability to achieve an erection, no matter how strong one’s sexual desire.
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