The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
Organic impotence refers to the inability to obtain an erection firm enough for vaginal penetration, or the inability to sustain the erection until completion of intercourse. In contrast to psychogenic impotence, which is impotence caused by anxiety, guilt, depression, or conflict around various sexual issues, organic impotence, the more common of the two categories of erectile dysfunction, is caused by physical problems. Ten to 20% of middle-aged men and a much higher percentage of elderly men are impotent. Aside from its importance as a common and distressing sexual problem, organic impotence may herald important medical problems.
It is important that physicians and other health care providers treating patients for chronic conditions periodically inquire into the sexual functioning of their patients and be prepared to offer counsel for those who experience erectile difficulties. Lack of sexual knowledge and anxiety about sexual performance are common contributing factors to erectile dysfunction. Education and reassurance may be helpful in preventing the cascade into serious erectile failure in individuals who experience minor erectile difficulty due to medications or common changes in erectile functioning associated with chronic illnesses or with aging.

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.
In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:
Treatments include psychotherapy, adopting a healthy lifestyle, oral phosphodiesterase type V (PDE5) inhibitors (Viagra, Levitra, Cialis, Stendra, and Staxyn), intraurethral prostaglandin E1 (MUSE), intracavernosal injections (prostaglandin E1 [Caverject, Edex], Bimix and Trimix), vacuum devices, penile prosthesis and vascular surgery, and (in some cases) changes in medications when appropriate.
The common PDE5 inhibitor drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra and Staxyn, the generic form), tadalafil (Cialis), or avanafil (Stendra). All of the currently approved PDE5 inhibitors work in the same way. They differ in the number of available doses, how quickly they work and last in your system, the dosing, and to some extent in the side effects. However, they generally share the same indications and contraindications. Currently, tadalafil is the only medication that patients can take on a daily basis and is approved for the treatment of both ED and BPH (benign enlargement of the prostate).
In one study, 9.6% reported ‘occasional’ erectile dysfunction, 8.9% reported erectile dysfunction occurring ‘often’, and 18.6% reported erectile dysfunction occurring ‘all the time’. Of these, only 11.6% had received treatment.In another study, only 14.1% of men reported that they had received treatment, despite experiencing erectile dysfunction for longer than 12 months.
An erection might last indefinitely if it weren’t for chemicals in the body called phosphodiesterases. They work at reversing the process trying to return the penis to being soft (i.e., flaccid). Usually there is a balance between the chemicals that result in an erection lasting for as long as it is needed, which allows the phosphodiesterases to do their job when they should and no sooner. You wouldn’t want an erection forever so it is a good thing that phosphodiesterases exist.

PDE5 inhibitors, the primary second-line therapy, have been the mainstay of ED treatment since the release of sildenafil (Viagra) in 1998, with the subsequent development of many others, and still more in the development stage. These medications do improve erectile quality for the majority of men, and they work by enhancing blood flow in the corpora cavernosa. These medications are generally used on demand and need to be taken about an hour before sexual intimacy. Tadalafil (Cialis) is longer acting and does come in a daily preparation potentially eliminating the ‘on-demand’ need. The daily dosing of tadalafil, 2.5–5 mg\day, has also been approved by the FDA for treatment of symptoms of BPH.41 PDE5 inhibitors are contraindicated in men taking nitrates, but otherwise PDE5 inhibitors are very safe and effective. When PDE5 inhibitors are coadministered with nitrates, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with CAD, so these drug combinations are commonly considered or encountered in clinical practice.42


The National Institutes of Health Consensus Development Conference on Impotence was convened to address (1) the prevalence and clinical, psychological, and social impact of erectile dysfunction; (2) the risk factors for erectile dysfunction and how they might be used in preventing its development; (3) the need for and appropriate diagnostic assessment and evaluation of patients with erectile dysfunction; (4) the efficacies and risks of behavioral, pharmacological, surgical, and other treatments for erectile dysfunction; (5) strategies for improving public and professional awareness and knowledge of erectile dysfunction; and (6) future directions for research in prevention, diagnosis, and management of erectile dysfunction. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement.
Along the same vein as stress, relationship troubles may also be at the root of some men’s erectile problems. Not trusting your partner, fears of birth control failure, or just genuinely not being emotionally attached to a partner could make it hard for a man to have an erection, The Huffington Post reported. Talking about issues within a relationship can help to resolve this problem.
Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
Tadalafil should not be used with alpha-blockers (except Flomax), medicines used to treat high blood pressure, and benign prostate hypertrophy (BPH) because the combination of tadalafil and an alpha-blocker may lower the blood pressure greatly and lead to dizziness and fainting. Examples of alpha-blockers include tamsulosin (Flomax), terazosin (Hytrin), doxazosin (Cardura), alfuzosin (Uroxatral), and prazosin (Minipress). Tamsulosin (Flomax) is the only alpha-blocker that patients can use safely with tadalafil. When tadalafil (20 mg) was given to healthy men taking 0.4 mg of Flomax daily, there was no significant decrease in blood pressure and so patients on this dose of tamsulosin (Flomax) can be prescribed tadalafil. The only alpha-blocker not tested with tadalafil is alfuzosin (Uroxatral), and no recommendations can be made regarding the interaction between the two.
The penis contains three cylinders, the two corpora cavernosa, which are on the top of the penis (see figure 1 below). These two cylinders are involved in erections. The third cylinder contains the urethra, the tube that the urine and ejaculate passes through, runs along the underside of the penis. The corpus spongiosum surrounds the urethra. Spongy tissue that has muscles, fibrous tissues, veins, and arteries within it makes up the corpora cavernosa. The inside of the corpora cavernosa is like a sponge, with potential spaces that can fill with blood and distend (known as sinusoids). A layer of tissue that is like Saran Wrap, called the tunica albuginea, surrounds the corpora. Veins located just under the tunica albuginea drain blood out of the penis.
#2 Physically exhausted. If you’ve been cranking it at the gym, haven’t been sleeping well, or you’ve been working your ass off at your job, getting tangled up with your lover for even more physically demanding activities may not sound ideal. Physical exhaustion has a direct effect on your ability to get aroused. The only fix for this one is to get some rest.
#6 It’s performance anxiety. Many men suffer from performance anxiety, and that’s another reason you can’t get hard. Simply put, you’re too nervous to get your dick up. And that’s okay, it happens! This is likely to happen if you haven’t had sex in a while or if you’re starting up with a new partner. Sex is supposed to be fun, but worrying over your prowess between the sheets can make sex the exact opposite of what’s it’s supposed to be. [Read: 13 ways to overcome sexual anxiety and perform]
Parasympathetic input allows erection by relaxation of trabecular smooth muscle and dilation of the helicine arteries of the penis. This leads to expansion of the lacunar spaces and entrapment of blood by compressing venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism. The tunica albuginea must have sufficient stiffness to compress the venules penetrating it so that venous outflow is blocked and sufficient tumescence and rigidity can occur.
The risk of impotence increases with age. It is four-fold higher in men in their 60s compared with those in their 40s according to a study published in the Journal of Urology (2000;163:460-463). Men with less education are also more likely to experience impotence, perhaps because they tend to have less healthy lifestyles, eat a less healthy diet, drink more and exercise less. Physical exercise tends to lessen the risk of impotence.
Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and the medications used to treat them. Aspects of an ageing man’s lifestyle and behaviour and androgen deficiency, most often decreasing testosterone levels, may affect sexual function as well. A study of men between the ages of 30 and 79 years showed that 24% had testosterone levels below 300 ng/dL and 5.6% had symptomatic androgen deficiency.2
An approach to the diagnosis and management of the impotent patient is presented in Figure 187.1. Apparent and likely causes of impotence should be considered first and, if possible, eliminated before the work-up continues. For instance, observing the patient for a few weeks off offending medication may be all that is necessary to establish the cause of impotence. When no obvious or remediable cause is present, the next step is based on the clinical impression of the likelihood of organic versus psychologic impotence. If the latter is considered more likely, it is perfectly reasonable to refer the patient directly for sexual therapy, with the option of reconsidering the diagnosis if, after appropriate therapy, there is no improvement. While an occasional patient with organic impotence will be misrouted, many more with psychogenic impotence will be spared an unnecessary and costly evaluation for organic causes. When organic impotence is likely, a serum testosterone level is the initial screening test for hypogonadism and should be obtained prior to urologic referral. Patients with low testosterone levels require further endocrine evaluations as depicted in Figure 187.1.
Vascular: Anything that affects the flow of blood to the penis can result in erectile dysfunction. The main culprit tends to be atherosclerosis, the condition that narrows arteries and which can result in poor blood circulation, high blood pressure, heart disease and stroke. Atherosclerosis causes about half the cases of erectile dysfunction in men over 50. Also, the veins through which the blood leaves the penis may not be working properly, allowing the blood to leave too soon.
Having learned a great deal more about erectile dysfunction including its risk factors and causes, you should be equipped to assess your own erectile function. If you have experienced erectile issues or you have some of the risk factors mentioned above, it may be worth making a trip to your doctor’s office. If you choose to seek help, give your doctor as much information as you can about your symptoms including their frequency and severity as well as the onset. With your doctor’s help, you can determine the best course of treatment to restore sexual function.
Dr Kenny du Toit is a urologist practicing in Rondebosch, Cape Town. He is also consultant at Tygerberg hospital, where he is a senior lecturer at Stellenbosch University. He is a member of the South African Urological Association, Colleges of Medicine South Africa and Société Internationale d’Urologie. Board registered with both the HPCSA (Health professions council of South Africa) and GMC (General medical council UK). He has a keen interest in oncology, kidney stones and erectile dysfunction.http://www.dutoiturology.co.za
The Massachusetts Male Aging Study (MMAS) documented an inverse correlation between ED risk and high-density lipoprotein (HDL) cholesterol levels but did not identify any effect from elevated total cholesterol levels. [15] Another study involving male subjects aged 45-54 years found a correlation with abnormal HDL cholesterol levels but also found a correlation with elevated total cholesterol levels. The MMAS included a preponderance of older men.

Total testosterone levels: Health care professionals should obtain a patient's blood samples for total testosterone levels in the early morning (before 8 a.m.) because the testosterone levels go up and down throughout the day. If you have a low testosterone level, a health care professional should check it again to confirm that it is truly low. In some men, a specialized test measuring the active form of testosterone (free or bioavailable testosterone) may be recommended.

Usually there will not be a specific treatment that will lead to the improvement of erectile dysfunction. However, there are treatments that will allow erections to happen and can be used to allow sexual activity to take place. There are three main types of treatments: non-invasive treatments such as tablet medicines and external devices (e.g. vacuum device); penile injections; or for men who have not had success with other treatments, surgery may be an option.

This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.
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