A national survey of sexual activity in the U.S. found that over 60% of people with partners were sexually active, including individuals with diabetes (27
). Similarly, 68.7% of 383 men with diabetes in the Look Ahead Study were sexually active (28
). The clinical observation that ED occurs at an earlier age and with greater frequency in men with diabetes compared with nondiabetic men is supported by multiple population-based epidemiological studies (27
) and by surveys of clinical practices (29
). In the Look Ahead Study (28
), 49.8% of men with diabetes reported mild or moderate ED. ED was associated with age (odds ratio 1.05, 95% CI 1.01–1.10), baseline hemoglobin A1c
(1.31, 1.05–1.63), hypertension (2.41, 1.34–4.36), and the metabolic syndrome (3.05, 1.31–7.11). There are few studies evaluating the prevalence of reduced libido in men with diabetes. Decreased sexual desire is primarily affected by the presence of ED and by depression. An observational study of 253 men with type 2 diabetes in Sri Lanka found that after excluding men with ED (33%), the prevalence of reduced libido was 25% (30
). In a population-based survey, premature ejaculation occurred in 36.3% (95% CI 26–48) of diabetic men and 22.9% (18–28.6) of nondiabetic men (27
). Inability to climax was reported in 26% of diabetic men versus 15.9% of nondiabetic men. Premature ejaculation was reported in 40% of the patients from Sri Lanka who did not have severe or complete ED (30
In the European Male Aging Study database of 3,369 men between the ages of 40 and 79 years, three sexual symptoms (poor morning erections, low sexual desire, and ED) had a syndromic relationship with decreased testosterone levels (18
). Moreover, in the European Male Aging Study, low serum testosterone was more frequent in men with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes. In studies from diabetes clinics, total, bioavailable, and free testosterone levels were low in men with type 2 diabetes (31
). When comparing testosterone levels in men with and without ED and type 2 diabetes, these investigators found significantly lower serum bioavailable testosterone (P
< 0.006) and free testosterone (P
< 0.027) in men with ED, but there was no significant difference in total testosterone levels. The lower the serum testosterone, the greater the severity of ED (32
). Corona et al. (33
) evaluated 1,200 men with ED and reported that 16% had type 2 diabetes. Serum total testosterone levels were below the reference range (<300 ng/dL or <10.4 nmol/L) in 24.5% of men with diabetes versus 12.6% of nondiabetic subjects (P
< 0.0001) after adjustment for age and BMI. In addition, hypogonadism in men with type 2 diabetes was associated with decreased sexual desire, more symptoms of depression, and lower luteinizing hormone levels.
ED in the past was ascribed to autonomic neuropathy or obliterative vascular disease; more recent studies identify endothelial dysfunction as an early abnormality that is potentially more amenable to therapy (20
). Animal studies have demonstrated testosterone effects on nerve structure and function, nitric oxide synthase activity, and smooth muscle growth and differentiation, which mediate penile erections (34
). Obesity and androgen deficiency are associated with increased proinflammatory cytokines, which also results in vascular endothelial dysfunction (20
Men with type 2 diabetes can have other causes of ED. In a study of 8,373 men with type 2 diabetes (35
), ED was associated with poor metabolic control, smoking, alcohol, antidepressants, antihypertensives, CVD medications, and histamine 2 receptor antagonists. There are multiple causes for low libido in the general population and in men with type 2 diabetes in addition to testosterone deficiency, including medications (e.g., serotonin reuptake inhibitors, antiandrogens), alcoholism, recreational drugs, fatigue, systemic illness, depression, relationship problems, other sexual dysfunction (fear of humiliation), hypoactive sexual disorder, and sexual aversion disorder.
The Look Ahead study reported that weight loss and increased physical activity were mildly beneficial in maintaining erections or improving ED in men with type 2 diabetes (36
). Although improvement in glucose control is associated with some improvement in erectile function in some studies, most clinicians have not found this to be a reliable and effective treatment for ED. The Testosterone Replacement in Older Men with either Metabolic Syndrome or Type 2 Diabetes (TIMES 2) trial recruited hypogonadal men with total testosterone <318 ng/dL (11 nmol/L) or free testosterone <6.5 ng/dL (225 pmol/L) and either metabolic syndrome or type 2 diabetes. Testosterone treatment improved libido (37
). Two meta-analyses of many clinical trials analyzed the effects of testosterone on different domains of sexual function (38
). Testosterone treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourse sessions, scores of erectile function, and overall sexual satisfaction in men with baseline serum testosterone <346 ng/dL (<12 nmol/L). The effects of testosterone on libido were more consistent than on erectile function. Testosterone replacement can restore nocturnal erections in hypogonadal men, but the effects are greater when testosterone and a phosphodiesterase (PDE)-5 inhibitor are administered together.
ED in many men with diabetes is improved by one of the PDE-5 inhibitors when used on demand. A recently published randomized double-blind placebo-controlled multicenter study evaluated the effectiveness of daily oral dosing of tadalafil in 298 men with diabetes and ED. Daily dosing of tadalafil showed significant improvement in vaginal penetration, completion of intercourse, and overall treatment satisfaction (40
). Testosterone replacement therapy has been reported to improve erections in men who did not respond satisfactorily to a PDE-5 inhibitor alone (41
). Larger trials using testosterone in addition to a PDE-5 inhibitor in hypogonadal men with ED who have testosterone levels <300 ng/dL (10.4 nmol/L) are needed.