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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.
Risks associated with injection therapy including bleeding, pain with injection, penile pain, priapism, and corporal fibrosis (scarring inside of the corpora cavernosa). There is also concern that repetitive injections in the same area could cause scar tissue to build up in the tunica albuginea that could create penile curvature. Thus, doctors recommended that one alternate sides with injection and perform injections no more frequent than every other day.
Erectile dysfunction can occur as a side effect of medication taken for another health condition. Common culprits are high blood pressure meds, antidepressants, some diuretics, beta-blockers, heart medication, cholesterol meds, antipsychotic drugs, hormone drugs, corticosteroids, chemotherapy, and medication for male pattern baldness, among others.

The National Institutes of Health estimates that erectile dysfunction strikes as many as 30 million men in the United States. Its prevalence does increase with age — 4 percent of men in their 50s are affected by ED, 17 percent in their 60s, and 47 percent of those over 75. But research has also found that 5 percent of those affected were between 20 and 39.

If you have symptoms of ED, it’s important to check with your doctor before trying any treatments on your own. This is because ED can be a sign of other health problems. For instance, heart disease or high cholesterol could cause ED symptoms. With a diagnosis, your doctor could recommend a number of steps that would likely improve both your heart health and your ED. These steps include lowering your cholesterol, reducing your weight, or taking medications to unclog your blood vessels.

Diabetes is one of the most common causes of ED. Men who have Diabetes are three times more likely to have Erectile Dysfunction than men who do not have Diabetes. Among men with ED, those with Diabetes are likely to have experienced the problem as much as 10 to 15 years earlier than men without Diabetes. A recent study of a clinic population revealed that 5% of the men with ED also had undiagnosed Diabetes. The risk of ED increases with the number of years you have Diabetes and the severity of your Diabetes. Even though 20% to 75% of men with Diabetes have ED, it can be successfully managed in almost all men. 

In many of these cases, a discussion between the physician, the man with erectile dysfunction, and possibly his partner can help to resolve the issues leading to treatment failure. For men who experience severe side effects, can’t take the drugs for other reasons (such as taking medicines such as nitroglycerin), or don’t respond in spite of further education on the correct use of the drugs, there are other treatment options that can help most men remain sexually active.
If the patient reports intermittent ability to obtain and maintain an erection, evaluation with combined injection and stimulation test (CIS) will give you additional diagnostic and potentially therapeutic answers. It will determine if he has adequate inflow to obtain erection and if he has adequate venous occlusive function to maintain erection. It may also provide reassurance to the patient that his anatomy is functional. However, it is well documented that due to increased sympathetic tone these young men will often require additional injection or a separate visit in order to respond appropriately with complete smooth muscle relaxation (7,20,21).
For many young men, performance anxiety plays a large role in erectile dysfunction. Other factors include money and work problems, as well as relationship issues and even issues about sexual orientation. Undiagnosed depression and post-traumatic stress disorder can cause erectile dysfunction--especially if the PTSD is related to a past sexual experience.
With all of that said, it should be clear that we lack evidence from nationally representative sex surveys to support claims about a massive increase in erectile difficulties among young men. It may be that reports of mild problems are increasing in this group (we need more data to know), but even if this is true, the data don’t suggest anything along the lines of, say, a 1000% increase.
Mental causes of sexual dysfunction include: depression, stress, anxiety and insomnia.  When one of these conditions leads to ED, usually once the condition is cured normal sexual behavior returns.  If you believe you have one of these conditions, see your doctor for an evaluation before beginning any treatment.  One side effect of antidepressants is erectile dysfunction.
Sildenafil (Viagra) was the first oral phosphodiesterase type 5 (PDE5) inhibitor approved by the FDA in the United States for the treatment of erectile dysfunction (it is not approved for women). Sildenafil inhibits PDE5, which is an enzyme that destroys cGMP. By inhibiting the destruction of cGMP by PDE5, sildenafil allows cGMP to accumulate. The cGMP in turn prolongs relaxation of the smooth muscle of the corpora cavernosa. Relaxation of the corpora cavernosa smooth muscle allows blood to flow into the penis resulting in increased engorgement of the penis. In short, sildenafil increases blood flow into the penis and decreases blood flow out of the penis.
Describing the epidemiology of ED in young men requires, first of all, defining what it is meant by youth. While the definition of old age is matter of discussion and a precise threshold does not exist, the most shared definition in Western Countries is age above 65 years (http://www.who.int/healthinfo/survey/ageingdefnolder/en/). Considering that most of the epidemiological studies on general populations aimed at studying health changes with age, enrol men more than 40 years, it seems reasonable to define young age as below 40 years. Epidemiological studies on erectile function, which considered the prevalence of ED according to age bands, consistently find a significant increase with ageing. Advancing age remains one of the most important unmodifiable risk factors for ED (1). Studies on ED mostly involve middle-aged and older men, with younger aged men often overlooked. In a multi-centre worldwide study, involving more than 27,000 men from eight countries, Rosen et al. (2) showed an ED prevalence of 8% among men aged 20–29 years and 11% among those aged 30–39 years. Most of the studies involving younger men and conducting age-stratified analyses have been performed in Europe, where the prevalence of ED in men younger than 40 years ranges between 1% to 10% (3-10). The prevalence reported in these studies is highly variable due to different methodologies used in defining ED, population accrual, acquisition of data and choice of tools for investigating erectile function. A smaller number of studies on this topic have been conducted outside Europe. Both in Australia (11,12) and in America (13-15), the available information suggests a similar range of prevalence of ED among young subjects, with the same extent of variability among studies. According to these data, ED in younger men, although still not extensively studied and largely overlooked by the scientific community, is a quite common condition. In a recent study conducted in a Urology Clinic, it has been observed that one out of four men seeking medical care for ED was younger than 40 years (16). In our Sexual Medicine and Andrology Unit, established in an Endocrinology setting at the University of Florence, medical consultations for younger men are infrequent, with a prevalence of men aged less than 40 years at only 14.1% of more than 3,000 men complaining of ED. However, when considering the new referrals to our Unit during the last 6 years, we can notice a progressive increase in prevalence of men below 40 years seeking medical care for ED (Figure 1). According to these data, ED is becoming a common concern even among young men, and the clinical practitioner in sexual medicine must become aware of how to manage the problem and avoid underestimating a symptom. The identification of ED in a young man may potentially provide a great deal of useful information that can help improve their quality and even length of life.
Diabetes is an example of an endocrine disease that can cause a person to experience impotence. Diabetes affects the body’s ability to utilize the hormone insulin. One of the side effects associated with chronic diabetes is nerve damage. This affects penis sensations. Other complications associated with diabetes are impaired blood flow and hormone levels. Both of these factors can contribute to impotence.
Similar to the general population (58), in subjects consulting for sexual dysfunction, T deficiency is progressively more prevalent as a function of age (50). In a series of 4,890 subjects consulting our Sexual Medicine and Andrology Unit for sexual dysfunction, one in five (19.6%) and one in three (29.4%) patients have total T below 10.4 and 12 nmol/L, respectively (60). Clinical correlates of T deficiency show different figures according to patient’s age. In fact, we previously demonstrated that in the youngest quartile (17–42 years old), but not in the oldest one (62–88 years old), severity of reported ED and penile blood flow impairment (dynamic peak systolic velocity) were not associated to decreasing testosterone levels (50). It is possible to speculate that, in young individuals, intercourse-related penile erection is such a complex phenomenon that other determinants (i.e., intrapsychic or relational) might mask its androgen regulation and that T deficiency produces greater sexual disturbances in subjects with greater frailty, such as older individuals. However, reported frequency of spontaneous erection and sexual thoughts were significantly decreased as a function of T decline even in younger subjects (50). Moreover, in young individuals low T was associated with a worse metabolic profile, including hypertriglyceridemia and increased waist circumference (50). Accordingly, the prevalence of MetS in the youngest quartile was clearly associated with T deficiency, as it was in the older quartiles (50). Therefore, T deficiency must be accurately verified in all subjects consulting for sexual dysfunction, even in the youngest ones.
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.
If the patient reports that PDE 5 inhibitors work poorly or inconsistently, we offer CIS to objectively assess erectile function and to provide diagnostic information. For the CIS, inject bimix (such as papaverine 30 mg/phentolamine 0.5 mg/mL—0.2–0.3 cc) and have the patient compress the injection site for 5 minutes. After 5 minutes, instruct the patient to self-stimulate, then assess his response to injection. One could also combine penile color duplex ultrasound (PCDU) with the CIS. However, PCDU is expensive, may not be covered by the patient’s insurance, and may require increased dosages of pharmacologic agents, such as trimix (papaverine 30 mg/phentolamine 0.5 mg/alprostadil 10 mg–0.5 cc) to obtain complete smooth muscle relaxation. This often requires reversal of erection using phenylephrine after the study. In rare patients who failed to achieve and maintain erection with 0.5 mL of trimix, we may proceed with pharmacologic cavernosography or pharmacologic arteriography depending on the results of PCDU.
When these drugs don't work, there are other options. Medications that dilate blood vessels, such as alprostadil, can be injected or deposited in the penis; they work in more than 80 percent of men with diabetes. Beyond that, penile implants can be an effective surgical solution. Implants are either malleable rods, which can be manually adjusted to the desired position, or inflatable cylinders that fill with fluid when a pump under the skin of the scrotum is pressed.

Unconventional CV risk factors, such as impaired erections during masturbation and reduced flaccid acceleration, are interesting parameters to implement in Sexual Medicine context, because they can help fill the gap of information on CV risk, left by the conventional risk factors (the so-called residual risk) (38). However, it should be recognized that not all the healthcare professionals who deal with the complaint of ED (i.e., general practitioners, diabetologists, cardiologists, sport physicians, nurses, etc.) have the facilities or competence for the specific assessment of these parameters. In contexts different than Sexual Medicine and Andrology, the assessment of conventional risk factors is certainly more convenient. Metabolic syndrome (MetS) represents a cluster of metabolic derangements easily and commonly evaluated in several different medical contexts. In a population of more than 600 subjects attending the Sexual Medicine and Andrology Unit of the University of Florence for ED, the presence of MetS was associated with an increased incidence of MACE during 4.3 years of follow-up in younger (first tertile of age: 18–52 years) (Figure 3, Panel A and B) but not in middle aged and older men (second and third tertiles of age: 53–60 and 61–88 years, respectively) (Figure 3, Panel B). Similar to MetS, the algorithms for estimating the risk of developing MACE are easily computed and they take into account factors largely available in a clinical setting. In Europe, the most commonly used algorithm is the SCORE, which takes into account age, smoking habits, systolic blood pressure and total cholesterol (26). These parameters are introduced in a calculation tool that returns the 10-year risk of developing the first MACE. The same estimated risk rate can obviously be derived from different combinations and extent of the single risk factors and, as aforementioned, age has a heavy weight in the amount of risk, even when the other parameters are normal. For overcoming this overestimation, the concept of vascular age, based on the predicted CV risk, has been introduced. Vascular age of a subjects with a specific CV risk profile corresponds to the chronological age of a subjects who has the same estimated risk but only due to chronological age, because of the absence of the other modifiable risk factors (i.e., a non-smoker, normotensive and normocholesterolemic subject) (39,40). Vascular age carries the advantage of easily and directly communicating the concept of high relative risk to patients, in particular to younger ones, who are by definition at low absolute risk (“Your CV risk is the same of a man that is 15 years older than you”). Based on this interesting and useful concept of vascular age, we recently studied the clinical consequences of having a high discrepancy between the estimated vascular and the actual chronological age in our population of men consulting for ED. In our sample, a greater difference between vascular and chronological age was associated with higher glucose and triglyceride levels as well as with impaired penile colour Doppler ultrasound parameters, suggesting a CV impairment (41). When evaluating the subset of men for whom information on incident MACE during a mean follow-up of 4.3 years was available, a greater difference between vascular and chronological age was associated with the incidence of MACE in younger, but not in older men (42).

Tadalafil (Cialis) is the third oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra) and vardenafil (Levitra), tadalafil inhibits PDE5 (as described earlier). Unlike the other PDE 5 inhibitors, patients should take tadalafil once daily and is approved for the treatment of BPH (benign enlargement of the prostate).
Burnett, whose lab has studied penile erection since the early 1990s, continues, "the insight here is tremendous because it speaks to fundamental biological and vascular" mechanisms of diabetes. "This paper gets back to the physiological relevance of hyperglycemia and how it affects erection.  We show here -- using erection as a model -- the vascular damage caused by diabetes and provide insights into vascular disease beyond this dysfunction," he adds.
This category of treatments includes external vacuum therapies: devices that go around the penis and produce erections by increasing the flow of blood in, while constricting the flow out. Such devices imitate a natural erection, and do not interfere with orgasm. External vacuum therapy mechanisms are approximately 95 percent successful in causing and sustaining an erection. All are portable, and costs range between $200-$500, covered under most insurance plans and Medicare Part B.
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