Rudy Bilous, MD, FRCP
Richard Donnelly, MD, PHD, FRCP, FRACP
Symptoms of sexual dysfunction affect both men and women with diabetes. The most common problem among men is erectile dysfunction (ED), which is defined as ‘the inability to achieve or maintain an erection sufficient for sexual intercourse’. ED occurs 10–15 years earlier in men with diabetes compared with men without diabetes, has a greater impact on quality of life than in men without diabetes and is less responsive to oral treatment. The prevalence of ED among diabetic men varies from 35% to 90%, and the age-adjusted incidence is two-fold higher in men with diabetes compared with those without. Advancing age and longer duration of diabetes are major risk factors for ED, but ED occurs more often in those men with macro- and/or microvascular and neuropathic complications. It is also associated with obesity, hypertension and antihypertensive therapies. In women, however, female sexual dysfunction (FSD) is related more closely to psychosocial factors than metabolic variables, and the presence of depression is a key predictor of FSD (Figure 22.1).
Erectile dysfunction is the most common sexual problem that affects men with diabetes. The age-related decline in erectile function is enhanced in diabetes, particularly in men with cardiovascular, microvascular or neuropathic complications (Figure 22.2). Depression is a common underlying problem that may predispose to, or exacerbate, ED and multiple drug therapies, especially antihypertensive drugs, often accentuate or unmask ED. One-third of men with diabetes and ED still experience morning erections, which suggests that there may also be a significant psychological component to their ED. The International Index of Erectile Function (IIEF), and its short form (IIEF-5), also known as the Sexual Health Inventory for Men (SHIM), are validated assessment tools for establishing the presence and severity of ED. In the erectile function domain of IIEF, men scoring 25 are considered not to have ED.
The principal neural mediator of the erectile response is nitric oxide (NO), which is released by vascular endothelial cells in response to cholinergic and non-cholinergic, non-adrenergic nerve fibre stimulation. NO-mediated relaxation of vascular smooth muscle in the corpus cavernosum of the penis leads to engorgement of the cavernosal space and compression of venous outflow. The postreceptor pathway that mediates NO-induced smooth muscle relaxation involves activation of the intracellular enzyme guanylate cyclase and formation of the second messenger cyclic guanosine monophosphate (cGMP). cGMP is broken down by phosphodiesterase-5 (PDE5), which converts cGMP to GMP (Figure 22.3).
In men with diabetes, multiple factors can contribute to ED (Figure 22.4). Macrovascular disease, hypertension and other CV risk factors (e.g. smoking) impair blood flow to the penis and cause endothelial dysfunction (in which the bio-availability of NO and/or the smooth muscle responsiveness to NO may be reduced). Microangiopathy in diabetes affects both somatic and autonomic nerve function, leading to neuropathy. Autonomic neuropathy is strongly associated with ED. Hypogonadism is often associated with type 2 diabetes (up to 35% of men with diabetes and ED may have serum total testosterone levels < 8 nmol/L). Although normal testosterone levels are needed for libido, the role of testosterone in erectile function is unclear. In addition, local and psychosocial factors can be important contributors.