Combination therapy has proven effective for some men who don’t respond adequately to oral medicines. The idea is to use two drugs with different mechanisms of action for better results. Commonly, sildenafil is used in combination with pellets of alprostadil (synthetic prostaglandin E1) that are inserted into the urethra (the tube in the penis that carries urine from the bladder to the outside of the body). Alprostadil also increases the blood supply to the penis, but by different means.
The association between psychiatric conditions and sexual dysfunctions, including ED, is well known. Data from population-based studies demonstrate a cross-sectional association between depressive symptoms and ED (65-68) and, among men seeking medical care for ED, depression is significantly associated with a greater severity of the impairment in erectile function (69,70). A meta-analysis of the available prospective studies has shown the role of depression as a significant risk factor for development of ED (71). However, the relationship seems to be bidirectional, as also ED has been associated with the occurrence of depression (72). In addition, treatment with PDE5i is related with an improvement in depressive symptoms (72). Most of this evidence comes from studies not specifically designed for the assessment of this relationship in younger men. However, few studies available in younger populations seem to confirm these results. In an internet-based survey, involving more than 800 North American medical students with a mean age of 25.7 years, ED was reported by 13% of them and it showed a significant association with depressive symptoms, whose frequency got higher as a function of ED severity (73). In a population of more than 2,500 very young Swiss men, aged 18–25 years, participating to a survey on sexual function while attending the medical screening for the evaluation of military capability, ED had a prevalence of 30%. Among the possible correlated conditions, mental health showed an independent association, besides the use of medications without medical prescription, a shorter sexual lifespan and impaired physical health (74). The results from this Swiss study were then prospectively extended on a sample of 3,700 men evaluated at baseline and 15.5 months later (75). Among a number of different possible predictors, including life-style, drug abuse, perceived physical fitness and BMI, only perceived impairment in mental health and depression, either newly occurred or continuously present, were associated with both persistence and development of ED (75). In a retrospective population-based study from Finland, involving almost 3,500 men aged 18–48 years, the role of depression as a significant predictor for ED was confirmed, but this study also showed that anxiety plays a significant role and that ED is significantly less frequent in men with a longer lasting sexual life, thus underlining the positive role of sexual experience and self-confidence (76). Anxiety is often involved in the pathogenesis of ED at the beginning of sexual life. In fact, anxiety can lead to an excessive focus on quality of erection, thus providing a cognitive distraction that negatively affects the arousal and consequently the erection itself (77-79). On the other hand, anxiety can result from one or more sexual failures, with loss of sexual confidence, increasing fears and avoidance for sexual experiences that, in the end, lead to an increased probability of new failures, thus creating a vicious circle (77). Cognitive distraction could be also provided by excessive worry for physical, and in particular genital, self-image. In fact, it has been proposed that when most mental energy is focused on monitoring body, psychological resources are distracted from sex, resulting in an impaired functioning (80,81). In line with this cognitive explanation, a recent study conducted on 367 military personnel younger than 40 years showed that a deteriorated genital self-image is associated with sexual anxiety which, in turn, is associated with a higher probability of sexual dysfunction (82).
Diabetes mellitus: Erectile dysfunction tends to develop 10 to 15 years earlier in diabetic men than among nondiabetic men. The increased risk of erectile dysfunction among men with diabetes mellitus may be due to the earlier onset and greater severity of atherosclerosis (hardening of the arteries) that narrows the arteries and thereby reduces the delivery of blood to the penis. Atherosclerosis can affect the arteries in the penis, as well as the arteries in the pelvis that supply the penile arteries. Diabetes mellitus also causes erectile dysfunction by damaging nerves that go to the penis, much like the effect of diabetes on nerves in other areas of the body (diabetic neuropathy). Diabetes can also affect the muscles in the penis, leading to troubles with erections. Smoking cigarettes, obesity, poor control of blood glucose levels, and having diabetes mellitus for a long time further increase the risk of erectile dysfunction in people with diabetes.
Cardiovascular diseases: The most common cause of cardiovascular diseases in the United States is atherosclerosis, the narrowing and hardening of arteries that reduces blood flow. Atherosclerosis (a type of vascular disease) typically affects arteries throughout the body; hypertension, high blood cholesterol levels, cigarette smoking, and diabetes mellitus aggravate atherosclerosis. Hardening of the arteries to the penis and pelvic organs, atherosclerosis, causes insufficient blood flow into the penis. There is a close correlation between the severity of atherosclerosis in the coronary arteries and erectile dysfunction. For example, men with more severe coronary artery atherosclerosis (hardening of the arteries in the heart) also tend to have more erectile dysfunction than men with mild or no coronary artery atherosclerosis. Some doctors suggest that men with new onset erectile dysfunction undergo evaluation for silent coronary artery diseases (advanced coronary artery atherosclerosis that has not yet caused angina or heart attacks).

Erectile dysfunction, also known as ED or impotence, is the inability to attain or maintain an erection of the penis adequate for the sexual satisfaction of both partners. It can be devastating to the self-esteem of a man and of his partner. As many as 30 million American men are afflicted on a continuing basis, and transient episodes affect nearly all adult males. But nearly all men who seek treatment find some measure of relief.
Neurologic illnesses leading to ED have been recently reviewed (64). The most common of them (i.e., consequences of prostatic surgery, stroke and Parkinson’s disease) are not typical of younger age and, similarly to conditions less common but more typical of younger men, such as spinal cord injury, multiple sclerosis and spina bifida, the clinical features of the underlying disease are clearly apparent, being ED one of the multiple manifestations, rather than a harbinger of a subtle condition. Diagnosis of neurologic origin of ED is often quite simple, based on medical history and physical exam. The clinical management is a multidimensional and coordinated work of rehabilitation and medical therapy, which includes ICI injection of vaso-relaxant drugs, vacuum device and surgery (64).
Peyronie's disease is a condition associated with ED. Peyronie's disease is thought to result from minor repetitive trauma to the penis that leads to scarring of the tunica albuginea. It is often associated with a palpable scar in the penis, plaque. The scarring can cause the penis to curve in the direction of the scar, along with painful erections and erectile dysfunction. Some treatments for Peyronie's disease (excision of the plaque and placement of new tissue in its place, grafting) may cause ED also.
Aging, liver and kidney problems, and concurrent use of certain medications (such as erythromycin [an antibiotic] and protease inhibitors for HIV) slows the metabolism (breakdown) of sildenafil. Slowed breakdown allows sildenafil to accumulate in the body and potentially may increase the risk of side effects. Therefore, in men over 65 years of age, in men with significant kidney and liver disease, and in men who also are taking medications called protease inhibitors, the doctor will initiate sildenafil at a lower dose (25 mg) to avoid accumulation of sildenafil in the body. A protease inhibitor ritonavir (Norvir) is especially potent in increasing the accumulation of sildenafil, thus men who are taking Norvir should not take sildenafil doses higher than 25 mg and at a frequency of no greater than once in 48 hours. Other medications that may affect the level of sildenafil include erythromycin and ketoconazole.
If you answer “yes” to any of these questions, your ED may well have a psychological link. To confirm this diagnosis, you may want to complete a full psychological evaluation. This is particularly important if you suspect that your ED has something to do with a mental health issue like anxiety or depression that might require additional treatment, either medical or psychosocial.
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.
The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of paired cylinders, which doctors surgically insert inside the penis. Patients can expand the cylinders using pressurized fluid (see figure 3). Tubes connect the cylinders to a fluid reservoir and pump, which doctors also surgically implant. The reservoir is usually in the pelvis. A doctor places the pump in the scrotum. By pressing on the pump, sterile fluid transfers from the reservoir into the cylinders in the penis. An erection is produced primarily by expansion of the width of the penis, however, one model can increase in length a small amount also. Lock-out valves in the tubing prevent the fluid from leaving the cylinder until a release valve is pressed. By pressing the relief valve and gently squeezing the penis, the fluid within the cylinders transfers back into the reservoir.
Sildenafil is available as oral tablets at doses of 25 mg, 50 mg, and 100 mg. Patients should take sildenafil approximately one hour before sexual activity. In some men, the onset of action of the drug may be as early as 11-20 minutes. It's best for men to take sildenafil on an empty stomach for best results since absorption and effectiveness of sildenafil can be diminished if it is taken shortly after a meal, particularly a meal that is high in fat. Sildenafil and the other PDE5 inhibitors don't cause an immediate erection. Sexual stimulation is necessary for these medications to work.
With coronary artery disease, a buildup of plaque inside the arteries can limit the amount of blood that’s able to flow through them. If the flow of oxygen-rich blood to your heart muscle is reduced or blocked by this hardening of the arteries, the result can be angina (chest pain) or a heart attack.17 Because the arteries that supply blood to the penis are much smaller than the ones that feed the heart, the problem may show up earlier as having difficulty getting an erection.18
Vacuum therapy devices have a few disadvantages. One must interrupt foreplay to use them. You must use the correct-size tension ring and remove it, to prevent penile bruising, after sustaining the erection for 30 minutes. Initial use may produce some soreness. Such devices may be unsuitable for men with certain bleeding disorders. In general, vacuum constriction devices are successful in management of long-term ED.
×