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ED + DM = CAD

Endothelial dysfunction is the link between ED, DM and CAD.

Diabetes is the second most common reason for erectile dysfunction, after vascular causes. According to the 2012 census, 15.5 million people suffered from erectile dysfunction, of which 50% was due to diabetes. Erectile dysfunction in diabetics occurs 10 to 15 years earlier than in men without diabetes. There are multiple factors that play into men with diabetes suffering from erectile dysfunction. Erectile dysfunction in diabetics can be determined by the age of the patient, duration of diabetes, degree of glycemic control, microvascular complications, and coexistence of cardiovascular diseases.

In a healthy adult, there are three mechanisms that lead to a penile erection. They include: neurologically mediated cavernosal arterial flow, cavernosal smooth muscle relaxation, and restriction of venous outflow. Neuropathy is a common symptom suffered by many diabetes patients. Hence, the neurologically mediated cavernosal arterial flow is impeded due to neuropathy, which eventually leads to erectile dysfunction. In addition, insulin resistance in people with diabetes leads to endothelial dysfunction and atherosclerosis, which impairs vasodilation and reduces penile inflow and increases outflow. Nitric oxide, which is released by endothelial cells, causes a normal penile erection. Due to the endothelial dysfunction in people with diabetes, the release of nitric oxide is impaired in men with erectile dysfunction, hence resulting in vasoconstriction, smooth muscle cell proliferation, and further complicating arterial flow. A study conducted by Yamanaka M et al., concluded that erectile dysfunction was observed in diabetes patients with worse glycemic control. It also added that in animal studies, diabetes-associated erectile dysfunction was relieved upon administration of insulin in the animals.

Diabetes and metabolic syndrome are correlated in regards to the damage of the vascular endothelium of the penis and other vascular beds that impair the release of nitric oxide, which leads to erectile dysfunction in men, as aforementioned. According to Kupelian et al., men over the age of 50 who have metabolic syndrome have a 48% increased risk of developing severe erectile dysfunction. In addition, the severity of erectile dysfunction increases as the number of components of metabolic syndrome increases (high blood pressure, excess fat around the waist, and increased cholesterol levels). Finally, low testosterone levels are independently associated with diabetes and metabolic syndrome that leads to erectile dysfunction. Low testosterone levels lead to obesity, dyslipidemia, insulin resistance, and hyperglycemia, all symptoms and characteristics of diabetes and metabolic syndrome. It is clear that low testosterone causes diabetes and metabolic syndrome, and vice versa, which eventually leads to erectile dysfunction. Hence, low testosterone level is an independent, additional risk factor for cardiovascular diseases in men suffering from diabetes and erectile dysfunction.

Endothelial dysfunction is the link between erectile dysfunction, diabetes mellitus, and coronary artery disease. In order to treat the three disease states, pharmacologic and lifestyle modifications need to be implemented to treat the endothelial dysfunction. Skeldon SC et al., concluded that patients with erectile dysfunction were more than twice as likely to develop diabetes mellitus.

The primary medications to treat erectile dysfunction are the phosphodiesterase type-5 (PDE-5) inhibitors. PDE-5 inhibitors require intact neurological responses; hence they are not as effective in people with diabetes for the same reasons as mentioned earlier. However, a meta-analysis conducted by Fink HA et al., showed a 63% improvement in diabetes patients with erectile dysfunction taking sildenafil vs. 19% taking placebo. Testosterone Replacement Therapy (TRT) in diabetes patients has shown to improve cardiovascular risk mortality and insulin resistance. It also improves responses to PDE-5 inhibitors in diabetic men. Corona G et al., concluded that treatments with PDE-5 inhibitors and statins have shown to reduce the risk of cardiovascular risks in diabetes patients. Non-pharmacological treatments for erectile dysfunction include vacuum erection devices (VED), intracavernosal drug injection (ICI), and penile prosthesis.

There are numerous lifestyle modifications suggested to treat metabolic syndrome that may help with erectile dysfunction in diabetics. Diet changes and improving physical activity habits have shown improvement of erectile dysfunction. According to Esposito et al., a Mediterranean  diet has shown to decrease erectile and endothelial dysfunctions in men with erectile dysfunction and metabolic syndrome. Exercise reduces cardiovascular risks among people with diabetes. It also increases nitric oxide production from the endothelial cells, reduces fat, and improves glycemic control.

Erectile dysfunction is prevalent in men with diabetes. Diabetes patients with erectile dysfunction are more likely to suffer from coronary artery disease. Although men with diabetes are more resistant to PDE-5 inhibitors, aggressive treatment with PDE-5 inhibitors and TRT’s has been shown to help treat erectile dysfunction.

Practice Pearls:

  • Men with diabetes who have erectile dysfunction are more likely to suffer from coronary artery disease and metabolic syndrome.
  • PDE-5 and TRT are pharmacologic treatments for erectile dysfunction in diabetes patients.
  • Patients with erectile dysfunction and diabetes should undergo a cardiovascular risk exam.

Walker C, Suarez-Sarmiento A. ED, Diabetes, and CV risks: Update on treatment, risk reduction. Urology Times. http://urologytimes.modernmedicine.com/urology-times/news/ed-diabetes-and-cv-risk-update-treatment-risk-reduction?page=0,0. January 6, 2016. Accessed January 13, 2016.

Yamanaka M, Shirai M, Shiina H, et al. Diabetes induced erectile dysfunction and apoptosis in penile crura are recovered by insulin treatment in rats. J Urol. 2003;170(1):291-7.

Kupelian V, Shabsigh R, Araujo AB, O’donnell AB, Mckinlay JB. Erectile dysfunction as a predictor of the metabolic syndrome in aging men: results from the Massachusetts Male Aging Study. J Urol. 2006;176(1):222-6.

Skeldon SC, Detsky AS, Goldenberg SL, Law MR. Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia. Ann Fam Med. 2015;13(4):331-5.

Fink HA, Macdonald R, Rutks IR, Nelson DB, Wilt TJ. Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med. 2002;162(12):1349-60.

Corona G, Mannucci E, Forti G, Maggi M. Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases. Int J Androl. 2009;32(6):587-98.

Esposito K, Ciotola M, Giugliano F, et al. Mediterranean diet improves erectile function in subjects with the metabolic syndrome. Int J Impot Res. 2006;18(4):405-10.
Researched and prepared by Sabair Pradhan, Doctor of Pharmacy Candidate USF College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE