Erectile Dysfunction (ED)

Content written by Irwin Goldstein MD


Erectile dysfunction, also known as impotence, is a crippling problem for millions of men. Erectile dysfunction is the inability to achieve and/or maintain an erection of sufficient rigidity and duration to allow for satisfactory vaginal intercourse. The initiation and maintenance of erection is a complex interplay of vascular, neural, hormonal and psychological factors. A problem involving any or all of these components can cause impotence. Erectile dysfunction can affect men of all ages; but its incidence increases with age. An estimated 1.9% of all 40 year old men are impotent, compared to 25% of all 65-year-old men. These figures include both organic and psychogenic impotence.

While the incidence of erectile dysfunction has remained relatively constant, therapeutic advances and greater public awareness of the problem has increased the number of men seeking treatment. During the past 30 years, through numerous advances in our understanding of the basic pathophysiology of impotence, a new era in the diagnosis and treatment of impotence has dawned. Improved diagnostic procedures and effective medical and surgical therapy are now available. The most recent advances in this field are the development of regenerative therapies, such as shockwave therapy, platelet rich plasma (PRP) and stem cell therapy. While all considered experimental, there have been numerous publications on the efficacy of shockwave therapy, but be forewarned, that there are radial wave devices making similar claims to that of shockwave without the science to support it. Ultimately research will show which of the regenerative therapies really work and for how long.


Because impotence is a functional disease, diagnostic evaluation and treatment can be tailored according to the patient’s desires and his physical and mental condition. This approach is known as the patient’s goal-directed approach to the diagnosis and treatment of impotence



Erectile dysfunction affects men of all ages; but its incidence increases with age. In the 1950’s, 90% of cases of erectile dysfunction were believed to be psychogenic. Current belief is that 50% of impotent patients have and underlying organic disorder, and in the older population, the percentage is probably higher. After appropriate history, physical and diagnostic evaluation has established the probable diagnosis of psychogenic erectile dysfunction, an attempt at psychosexual therapy is indicated. Among the goals of sex therapy intervention are the correction of misinformation and myths, establishment of mutual responsibility for satisfaction and the elimination of interference in the form of performance demand or anxiety.

There are few controlled studies establishing the effectiveness of behavior therapy for functional erectile dysfunction. Patients are often resistant to referral. Seagraves reported that 38% of patients referred to psychiatry never contacted the clinic, and of those that did, 83 percent refused therapy or terminated therapy early. The establishment of a satellite psychiatry service in the urology clinic may lead to an improved rate of success.


In 2010, low-intensity shockwave therapy (Li-SWT) was first used in Europe as a novel, minimally-invasive disease modification treatment strategy for ED.  Li-SWT has been used therapeutically in other fields of medicine, including in the treatment of cardiac or limb ischemia, diabetic foot ulcers, and wound healing.  Li-SWT has been shown in multiple publications to improve impaired erectile function in a variety of animal models of ED.  It is proposed that Li-SWT acts possibly through stimulation of mechanosensors, inducing the activation of neo-angiogenesis processes, recruitment and activation of stem cell progenitor cells, improvement of microcirculation, nerve regeneration, remodeling of erectile tissue with increase in the muscle/collagen ratio, and reducing inflammatory and cellular stress responses.  The hypothesized biologic effect of Li-SWT would result in a decrease of corporal erectile tissue fibrosis.  This would be evident as reduced erectile tissue inhomogeneity on Grayscale ultrasound.  The other hypothesized biologic effect would be an increase cavernosal arterial perfusion pressure.  This would be evident as increased cavernosal arterial peak systolic velocity on Duplex Doppler ultrasound. The European Urological Association has listed Li-SWT as a treatment for ED.  

The low-intensity shockwaves used in most Li-SWT treatment protocols published to date emit an energy density of approximately 0.09 mJ/mm2.  In contrast, kidney stone lithotripsy energy densities are approximately 0.9 mJ/mm2; this is 10 times higher that used for ED. In general, Li-SWT treatment protocols provide 1 treatment session per week over the course of 6 weeks. In general, several thousand shockwaves are delivered to multiple areas of the penis, with each treatment session lasting approximately 20-30 minutes.   In general, shockwaves are delivered by a hand-held probe. In general, treatment is offered in an outpatient setting with no analgesia needed.  

At San Diego Sexual Medicine we utilize the Urogold 100™ shockwave device which is FDA cleared for improved blood flow, pain amelioration and connective tissue activation.  Several basic science studies examining the effects of low intensity penile shockwave on erectile tissue have utilized the Urogold100™ electrohydraulic shockwave device. Multiple health care providers have presented positive erectile dysfunction outcome data after treatment with Urogold 100™ shockwave device. No side effects have been reported.  


Platelet rich plasma therapy for erectile dysfunction is an experimental therapy that delivers your own body's plasma to the erection tissue, hypothesized to encourage the release of important growth factors into the penile tissues that decrease inflammation, increase blood flow and increase penile smooth muscle cell function.


The first effective oral medication for erectile dysfunction, sildenafil (Viagra) was introduced in March of 1998; this was the dawn of effective therapy using a simple pill and changed the treatment of men with erectile dysfunction forever. For the first time there was a safe and effective therapy that could be obtained by primary care physicians and health care providers. It was no longer necessary to go to see a specialist. This was followed closely in 2003 with vardenafil (Levitra) and tadalafil (Cialis). As the market for these drugs has increased, it has been important to identify the safety, efficacy and limitations of these drugs. When choosing a PDE-5 inhibitor for your patient, it is important to know the onset of action, efficacy and duration. Studies usually will define the maximal plasma concentration (Cmax), time to reach this plasma concentration (Tmax) and the plasma half-life (t ½). How well these laboratory findings correlate to clinical findings is sometimes difficult to determine and the measuring tool most commonly used to evaluate efficacy is the IIEF erectile function domain score.


The most studied of these drugs is sildenafil (Viagra). In several placebo controlled, randomized trials, this drug has been shown to improve erectile function. The pivotal study for sildenafil was published in 1998, which showed a clinically and statistically significant improvement in IIEF erectile function domain scores for men suffering from ED for greater than 5 years. The onset of action of sildenafil is approximately 20 minutes with a reported t ½ of 3 to 5 hours and duration of action as long as 12 hours. The important thing about sildenafil is that it should not be taken with a high-fat meal because this will decrease the absorption of the medication.


The FDA approved vardenafil (Levitra) in 2003 after a study of 805 men with ED showed a clinically and statistically significant improvement in IIEF scores when compared to placebo. In this study, different doses were evaluated and men were broken up into mild, moderate and severe ED. Approximately 40% of the moderate and severe ED men had improvement with the highest dose and over 79% of the mild ED men had improvement. Vardenafil is quickly absorbed with a Tmax of 45 minutes and a reported t ½ of 4-5 hours. Onset of action has been recorded as early as 10 minutes. Just as in sildenafil, it is recommended that high-fat meals are avoided.


Tadalafil (Cialis) was approved at the same time as vardenafil and acquired the nickname “the weekend pill” because of the longer half-life than the other two drugs in its class. The Tmax of tadalafil is closer to 2 hours and the t ½ is 17.5 hours with a clinical efficacy reported of 12 to 36 hours19. Several studies showed the efficacy of tadalafil and the most important study involved 1112 patients with mean duration of ED >1 year. In this group over 80% of the men had improved erections up to 36 hours after administration of the drug. One other thing that differs from sildenafil and vardenafil is that the absorption of tadalafil does not seem to be affected by high-fat meals so there are no dietary restrictions.

Side effects of all three drugs include headache, flushing, dyspepsia and rhinitis. It has been shown with continued vardenafil use, these side effects are reduced significantly after the first few weeks. There is less than a 5% drop out rate secondary to side effects.


There are two things to warn your patients about with the use of these drugs (PDE-5 inhibitors.) The first is that these drugs cannot be taken with nitrates. When sildenafil has been used, it is recommended to wait at least 24 hours and when tadalafil has been used, 48 hours is recommended. The results can be severe hypotension and all patients need to be aware of this contraindication. The second thing is that patients need to be counseled to seek medical attention if they have any visual changes. Current recommendations are not to change prescription habits but to advise patients to seek medical attention if they experience visual changes while taking a PDE-5 inhibitor.

Initially there were concerns about the cardiovascular safety of these drugs. It is known that sildenafil can act as a mild vasodilator and there are warnings about orthostatic hypotension with concomitant use of a-blockers. The use of PDE-5 inhibitors is not contraindicated in men who are also on alpha-blockers, they just need to be stabilized on this blood pressure medication prior to initiation of therapy. There were also concerns that use of PDE-5 inhibitors would increase cardiovascular events. The safety of these drugs has been confirmed in several controlled trials with no increase in myocardial ischemic events or overall mortality compared to the general population. While there has been no increase of cardiovascular events associated with the use of these drugs, it is important to do a thorough cardiovascular history and exam prior to prescribing PDE-5 inhibitors as the risk factors are shared for ED and cardiovascular disease.

Yohimbine has been considered an aphrodisiac for many years. An alpha 2 blocker, yohimbine had only moderate success (compared to placebo) in treating erectile dysfunction patients in several recent clinical studies. The response rate seems higher in the patients with psychogenic erectile dysfunction (31% complete and 31% partial) than organic erectile dysfunction (18% complete and 27% partial(28). It was often prescribed for patients seeking treatment for erectile dysfunction because of its relatively mild side effects (anxiety, nervousness, slight increase of blood pressure). The relative low response rate along with its unpredictability are the major disadvantages of Yohimbine and it has largely been abandoned.


After diabetes, the three most common endocrine conditions associated with erectile dysfunction are:

  1. Hypergonadotropic hypogonadism: Loss of end organ androgen production may be the result of infection, trauma, surgery or congenital abnormalities of sex chromosome or gonadal differentiation. Impotent men may present with depressed serum testosterone and elevated serum gonadotropins. The treatment is testosterone replacement using gels, injections or subcutaneous pellets. While sublingual or oral testosterone may be simpler to use, unpredictable absorption from the gastrointestinal tract and occasional cases of hepatic dysfunction make parenteral therapy the prefered method.
  2. Hypogonadotropic hypogonadism: Loss of gonadotropin production with secondary decrease in end organ androgen production, this condition is rare and often associated with prolactinomas or Kallmann’s syndrome. Treatment is directed at eliminating the primary cause and the institution of supplementary parenteral testosterone therapy.
  3. Hyperprolactinemia: Most patients suffering from this condition are found to have an iatrogenic cause. Many medications are known to cause overproduction of prolactin (estrogens, reserpine, phenothiazine or alpha–methydopa); secondary erectile dysfunction may result. Only a small portion of patients with erectile dysfunction due to hyperprolactinemia have pituitary tumors. In those patients with iatrogenic hyperprolactinemia, treatment consists of a change of medication. Patients with pituitary tumors may be treated with bromocryptine (Parlodel) or pituitary surgery.

Self-injection of papaverine or papaverine with phentolamine has become a popular treatment. Sexual stimulation will enhance the response (64% of impotent patients will improve the quality of their erection with self stimulation) and lessen the amount of agent required to induce erection. Nearly all patients with neurogenic erectile dysfunction, and about 60–70% in patients with vasculogenic erectile dysfunction respond to intracavernous injections. The dosage ranges from 0.1 ml of papaverine alone to 1.5 ml of the mixture of papaverine with phentolamine.

Intracavernous injection of prostaglandin E1 was introduced in Japan with encouraging results. Alprostadil (prostaglandin E1) was FDA approved and is now marketed for use as Caverject™ or Edex™ Response rates may reach as high as 86% in some patients treated with 20µgm of PGE1; rates of 60 to 80% full or partial response can be seen The dosage ranges from 1–30 µg. The major side effect is painful erection in about 20 percent of patients, which may be related to the concentration of the drug or penile neuropathy.

The major complications of self-injection therapy are priapism and fibrosis of the erectile tissues but these are quite rare when used correctly. It is common for men on self injection to develop painless nodules at the injection sites. If treated early, priapism can easily be reversed by aspiration and/or injection of diluted alpha adrenergics. Other minor complications include hematoma, drop of blood pressure, vasovagal reflex, metallic taste, subcutaneous injection, and mild chemical hepatitis.


Several vacuum constriction devices (VCD) are now available commercially. The standard VCD consists of a suction cylinder and pump to induce erection and a constricting band placed at the base of the penis to maintain the erection-like state after the suction device is removed. Initial clinical models required a fair degree of manual dexterity for use, newer models contain built in pumps in the vacuum cylinder or are motorized. To prevent ischemia of the penis, the patient is advised to remove the constriction band within 30 minutes.

Satisfactory use of these devices has been reported in a large number of patients. A retrospective study of 1,517 patients responding to a questionnaire revealed that 92% achieved an erection or erect like state sufficient for intercourse, and 77% were able to have intercourse at least every 2 weeks Complications may include red spots (27%), brusing (10%), initial penile pain (41%), ejaculatory difficulty, usually from erectile pivoting(12%), dusky discoloration of the tip of the penis, penile numbness and trapping of the semen.


Simultaneous injection of intracavernous vasodilating drugs with use of a vacuum constriction device may be of help to patients who could not achieve adequate erection with either therapy alone. This is especially helpful in patients with severe vascular disease and those with fibrosis of the erectile tissues secondary to priapism. An additional subgroup of patients who may benefit from the use of the VCD are those who have failed penile prosthesis insertion. We have found that the use of VCD in this group of patient markedly improves the erection obtained by intracavernous injection alone.


Before the introduction of intracavernous vasodilator injection therapy, testosterone injections or placement of a penile prosthesis were the only effective treatment for erectile dysfunction besides psychologic counselling. Tens of thousands were implanted, with indications that were somewhat loose. Any patient with a history of poor erections or a poor tracing on nocturnal penile tumescence testing was a candidate. Patients with good nocturnal tumescence who failed to improve with psychotherapy were also candidates. Today the high success rate of less invasive therapies such as intracavernous injection and vacuum constriction devices (VCD) has dramatically reduced the incidence of prosthetic surgery.

There are two major categories of penile prostheses; 1) the semirigid prosthesis and 2) the inflatable prosthesis. The semirigid prosthesis has the advantage of simple design and ease of insertion. Further, because of its simple design it is resistant to mechanical failure. The disadvantage of the semirigid prosthesis is its permanently erect state, and lack of concealability. The inflatable prosthesis has the advantage that it both elongates and expands in girth while inflated, which results in a more natural erection. However, the complexity of its design and the need for a fluid reservoir make placement more exacting and increase the chance for mechanical failure. Over the years, numerous modifications have been made to improve the concealment (Semirigid) and durability (inflatable) of the penile prostheses and reduce the complication rate of the prosthetic surgery. The complications include device failure, perforation, infection, persistent pain, aneurysmal dilation of the inflatable devices, etc. With the improved design and more durable material, the complication rate has been significantly reduced over the past few years and the patient–partner satisfaction rate approaches 90%.