eMedicine Specialties > Urology > Erectile Dysfunction, Premature Ejaculation, and Sexual Disorders

Erectile Dysfunction: Treatment & Medication

Author: Stanley A Brosman, MD, Clinical Professor, Department of Urology, University of California at Los Angeles Medical School
Contributor Information and Disclosures

Updated: Jul 22, 2009

Treatment

Medical Care

After all the information regarding the patient's status has been gathered, the various options in management can be discussed. This is best completed in the presence of the patient and his partner. Enough options are available that every man who wants to be sexually active can do so. These include sexual counseling if no organic causes can be found for the dysfunction, oral medications, external vacuum devices, or some type of invasive therapy, including the use of intracavernosal injection therapy or the Medicated Urethral System for Erections (MUSE), which is an intraurethral suppository. One of the most difficult aspects is teaching men that sex entails more than simply achieving an erection.

The most common form of management in current practice is the use of one of the oral PDE-5 inhibitors. If one agent does not work adequately at its maximum dosage, another agent should be tried. Trying these medications 3-4 times is sometimes necessary before concluding that the therapy is ineffective. Men who have a vascular-leak (venous leak) phenomenon may need a constriction device placed at the base of the penis to maintain the erection, which may be effective by itself or in combination with a PDE-5 inhibitor. In selected cases, combination therapy with one of the PDE-5 inhibitors plus Yohimbine, MUSE, or intracavernosal injections can be tried. Although some men have taken two different PDE-5 inhibitors simultaneously, no evidence suggests any benefit and the risk of significant adverse effects is greatly enhanced. However, the use of both a shorter-acting agent and a longer-acting agent is not unreasonable at appropriate times and intervals as long as they are not taken together.

Possible blindness due to nonarteritic anterior ischemic optic neuropathy and cilioretinal artery occlusion caused by PDE-5 inhibitors has been a concern. This is an extremely rare event, with only a handful of reported cases from the tens of millions of patients using PDE-5 inhibitor medications. This risk may be increased if the PDE-5 medication is misused or overdosed.

If none of these nonsurgical therapies is satisfactory to the patient and his partner, a discussion regarding the relative merits and adverse effects associated with penile implants can be introduced. Some data indicate an additional benefit in some men who have an implant but also take a PDE-5 inhibitor. Sexual stimulation and sensation is enhanced.

Psychogenic impotence is relatively uncommon. It is characterized objectively by the presence of good nocturnal and morning erections and negative findings from all other tests. During the interview, a history of highly variable erections that can be totally absent one day but virtually normal the next suggests a psychogenic cause. Virtually 100% of men with severe depression have erectile dysfunction (ED). Sildenafil (Viagra) works well for psychogenic ED; other treatment modalities are also effective because the tissues, nerves, hormone levels, and vasculature are normal. The authors usually recommend a full psychological evaluation in these patients so that the underlying etiology can be identified and treated appropriately rather than just treating the symptom of ED. Therefore, the authors defer treatment of the patient's ED until he has begun psychological testing and therapy for the underlying problem.

Vacuum devices

As a relatively inexpensive method for producing an erection, vacuum devices to draw blood into the penis have been used for many years. These are plastic cylinders that are placed over the penis. Air is pumped out, causing a partial vacuum. Releasing the vacuum after a few minutes and then reapplying the vacuum sometimes gives a better result. After an erection is obtained, a constricting band is placed at the base of the penis. This technique is effective in 60-90% of patients and maintains the erection for up to 30 minutes. (The erection would last until the constricting band is released, but longer than 30 min is not recommended.)

These devices are generally safe, but hematomas, petechia, and ecchymosis have been reported. Other adverse effects include pain, lower penile temperature, numbness, absent or painful ejaculation, and pulling of scrotal tissue into the cylinder, where it becomes trapped under the ring. Many of these problems can be alleviated by proper selection of the tension rings and cylinders. The devices are very reliable and seem to work better with increased use and practice. They can be operated and used quickly with experience but still tend to be less romantic than other therapeutic options.

One drawback to the use of these external vacuum devices is the need to assemble the equipment and the difficulty in transporting it. Many patients lose interest in using the device because of the preparations that are necessary, the lack of easy transportability, the inability to hide the tension ring, and the relative lack of spontaneity. Approximately half the men who use a vacuum device obtain very good erections, but only half of these men consistently use the device for a prolonged period.

Sildenafil (Viagra)

Sildenafil is the first oral agent to be well documented as an effective form of treatment for men experiencing ED. Since its introduction in March, 1998, no other therapy for ED has achieved such prominent public recognition. Of the 250,000 American physicians who have written prescriptions for sildenafil, 14% have been written by urologists and 82% by nonurologists.

Controlled clinical trials in selected populations of men with ED have demonstrated the efficacy of sildenafil in helping men achieve and maintain erections. The efficacy of sildenafil was demonstrated in 21 randomized, double-blind, placebo-controlled studies of up to 6 months' duration involving more than 3000 male subjects aged 20-87 years.

Sildenafil is a potent inhibitor of PDE-5, the enzyme that acts in the corpora to break down cGMP. This action is mediated by the secondary neurotransmitter NO, which is primarily responsible for smooth muscle relaxation within the corpora cavernosa. The inhibition of PDE-5 slows the degradation of NO, which enhances its effect. This permits the development of an improved and sustainable erection.

Sildenafil has been demonstrated to improve erectile function in diabetic patients, hypertensive patients, post–transurethral resection of the prostrate patients, radical prostatectomy patients following radiation therapy for prostate cancer, geriatric patients, spinal cord injury patients, and depression patients. As many as 66-90% of patients with ED secondary to brachytherapy or external beam radiation therapy for prostate cancer have significant improvements in erectile function.

The long-term efficacy of sildenafil has been shown in a 48-month, open-label, noncontrolled, flexible-dose study. One year following the initiation of therapy, efficacy and satisfaction continued to be significantly improved.

Safety concerns and adverse effects have been studied carefully. The most common adverse effects are headaches and upper GI distress. These are not usually severe and are self-limited when the drug is stopped. Sildenafil is a mild inhibitor of phosphodiesterase type 6, which is found in the retina. This inhibition is manifested by a blue haze at the periphery of the field of vision but is not dangerous. Very few patients have stopped taking sildenafil because of this effect.

The cardiac effects associated with sildenafil have been studied extensively. Sildenafil is absolutely contraindicated in patients taking nitrates such as nitroglycerin or isosorbide. This is because sildenafil, like the other PDE-5 inhibitor medications, can potentiate the vasodilatory effects of the nitrate-based medication, resulting in an exaggerated vasodilatory effect that is potentially dangerous. Patients with serious cardiac disease, with exertional angina, or taking multiple antihypertensive medications are advised to seek the advice of a cardiologist before beginning therapy with sildenafil. A number of studies examining the cardiac effects of sildenafil have conclusively shown that no adverse consequences exist under normal circumstances.

In the original clinical trials involving more than 3000 male subjects, the incidence of myocardial infarction and myocardial ischemia was not significantly different between those who took a placebo and those who took sildenafil. The same was true when postural hypotension was evaluated. Exertion associated with sexual activity has been documented to increase the chances of ischemic events and myocardial infarction. Men with ischemic heart disease who do not take sildenafil have as much as a 2-fold increase in cardiac events compared with healthy men.

Sildenafil is available in 3 doses: 25 mg, 50 mg, and 100 mg. The starting dose depends on the clinical situation. A man in his fifth decade of life with mild sexual dysfunction that is probably related to psychological factors can start on the 25-mg dose. Men with moderate-to-severe ED can begin at the 50-mg dose, and, after testing the effect of the drug on at least 3 occasions (although 5-6 tries is recommended), the dose can be modified. Men with severe ED can start on the 100-mg dose; these men are not likely to achieve a satisfactory response, but they should make 3-4 attempts before starting another form of therapy.

Sildenafil should be taken on an empty stomach approximately 30-60 minutes prior to sexual intercourse. This agent is not intended to be taken daily. Sexual stimulation is necessary to produce an erection. An increased ability to obtain erections can last up to 24 hours but is usually limited to 6-8 hours.

Patients who are refractory to sildenafil may benefit from vardenafil or tadalafil therapy. If none of these is successful, combine the agent with an injection of prostaglandin E-1. Gutierrez et al demonstrated that this combination was more effective than either one alone. Other successful combinations include using a PDE-5 inhibitor with MUSE.⁵

Vardenafil (Levitra)

This agent, which is available in 5-mg, 10-mg, and 20-mg doses, became available in 2003. These lower doses are effective because this agent has a 9-fold increase in selectivity for the specific receptor responsible for NO release in the penis. This agent can act within 20 minutes. Vardenafil has similar efficacy, side effects, and limitations as sildenafil but may be less bothered by food.

Tadalafil (Cialis)

This is available in 5-mg, 10-mg, and 20-mg doses. This agent has an extended period of responsiveness that can last 36 hours or longer in some men. This agent can be ingested without food restrictions. The other two oral agents can act within an hour; in contrast, tadalafil usually requires a 1 to 2-hour waiting period. The flexibility afforded by this agent takes away the concern about the timing of intercourse. Unlike the other agents, tadalafil has a potential back-pain side effect thought to be due to a PDE-11 effect. A single, small daily dose of tadalafil is being studied as a possible therapeutic alternative to intermittent dosing. This would eliminate the need for carefully timing the taking of the medication and would allow increased freedom of action by patients.

Tadalafil has been shown to improve endothelial function in men with ED. Rosano et al studied brachial artery blood flow in 32 men with increased cardiovascular risk factors.⁶ They found that blood flow was significantly improved and this benefit remained for 2 weeks after cessation of the medication.

Yohimbine

This oral agent has been available for many years. It has both a central and a peripheral effect. Its efficacy has been questioned because even in properly conducted, well-controlled studies, yohimbine is only slightly better than placebo. A renewed interest in this agent has occurred, particularly when combined with sildenafil or some of the other oral agents.

Yohimbine is a safe agent with few known adverse effects. It is administered daily in a dose of 5.4 mg (1 tab) 3 times/d.

Apomorphine (Uprima)

Apomorphine is a sublingual agent that is not approved by the US Food and Drug Administration (FDA). Apomorphine has a central effect on the hypothalamus. It is a D1/D2 dopamine receptor agonist from the apomorphine (nonopiate) drug class. This agent has been shown to specifically activate c-fos gene expression in the paraventricular and supraoptic nuclei of the hypothalamus in animal models. These areas are known to be involved with penile erections.

The administration of apomorphine by subcutaneous, oral, and intranasal routes results in variable effects on erectile function and moderate-to-severe adverse effects, primarily nausea and vomiting. A slow-release sublingual formulation has demonstrated erectile enhancement benefits with a significant reduction in adverse effects.

Of 977 subjects who received double-blind medication, 774 (79.2%) completed the course of treatment. Several doses were used, but patients in all of the apomorphine dose groups reported erections firm enough for penetration more often than those taking placebo (P <.01). When separated according to dose, firm erections were reported by 45% versus 35% of the control group with the 2-mg dose. The 4-mg dose elicited positive responses in 55%, compared with 36% in the placebo group. With the 6-mg dose, 60% reported positive responses, compared with 32% in control subjects. Adverse events occurring in 10% or more of the patients in any group were nausea, sweating, dizziness, somnolence, vomiting, yawning, and asthenia. Most of these were considered mild to moderate in severity. Nausea was the most common adverse effect, which was found to be dose-related and reducible with repeated exposure to the drug.

Phentolamine (Vasomax)

This agent is an alpha-receptor blocker that has not been approved by the FDA for the treatment of ED but has undergone limited clinical testing.

Detumescence is influenced by alpha-adrenergic tone. Alpha-1 receptors predominate in the trabecular smooth muscle cells of the corpora cavernosa, alpha-2 receptors are the predominant receptors in the cavernosal arteries, and both alpha-1 and alpha-2 receptors are present in the circumflex and deep cavernosal veins.

Two placebo-controlled trials reported effectiveness in 42% and 32% of patients taking 50 mg compared with 9% and 13% in the control group, respectively. The erections occurred in 20-30 minutes. The drug was well tolerated, with mild-to-moderate adverse effects, usually headaches or lightheadedness, occurring in less than 10% of patients.

Androgens

Men who present with diminished libido and ED may be found to have low serum testosterone levels. Hormone replacement may be of benefit to those with severe hypogonadism and possibly as adjunctive therapy when other treatments are unsuccessful by themselves. Libido and an overall sense of well-being are likely to improve when serum testosterone levels are restored to the reference range.

Replacement androgens are available in oral, injectable, gels and transdermal preparations. Oral therapy is the least effective and the most likely to be associated with hepatotoxicity, even though this is a relatively small risk. Parenteral therapy is most likely to restore androgen levels to the reference range, but this therapy requires periodic injections, usually every 2 weeks, to sustain an effective level. Peak and trough levels are suggested when using injectable agents to avoid symptomatic troughs and supernormal peak levels. Weekly injections using lower doses can be used to minimize the wide swings in blood levels with less frequent dosing. Skin patches deliver a sustained dose and are generally accepted by patients. Androgen creams (AndroGel and Testim) are now available for daily topical use for male hypogonadism and have the advantage of minimizing the peaks and troughs of injectable agents. However, they require daily dosing and are relatively expensive.

The use of exogenous androgens suppresses natural androgen production. Elevating serum androgen levels has the potential to stimulate prostate growth and may increase the risk of activating a latent cancer. Periodic prostate examinations, including digital rectal examinations, prostate-specific antigen determinations, and blood counts (ie, CBC counts), are recommended in all patients receiving supplemental androgens. Obtaining a testosterone level while on therapy is also suggested to optimize the dosage.

Injection therapy

While many substances are touted as aphrodisiacs, the modern age of pharmacotherapy began in 1993 when the injection of papaverine, an alpha-receptor blocker that produces vasodilatation, was shown to produce erections when injected directly into the corpora cavernosa. Soon afterwards, other vasodilators, such as PGE1 and phentolamine (Regitine), were demonstrated to be effective either as single agents or in combination.

Self-injection of these agents has been of enormous benefit because they represent the most effective way to achieve erections in a wide variety of men who otherwise would be unable to achieve adequately rigid erections.

If the vasculature within the corpora cavernosa is healthy, the use of injectable agents is almost always effective. Patients need to be carefully instructed on how to perform the injections. The dosage is adjusted to achieve an erection with adequate rigidity for no more than 90 minutes. Up to 40 mcg of alprostadil can be used. An abnormal finding after biothesiometry testing has been suggested as an indicator of possible heightened sensitivity to intracavernosal injections, but this is unproven.

Alprostadil, a synthetic PGE1, is the most common single agent used for intracavernosal injections. When combined with papaverine and Regitine, the mixture is called Trimix and it has roughly twice the efficacy of alprostadil alone. In one study of 683 men, 94% reported having erections suitable for penetration after alprostadil injections. The main adverse effects are a painful erection, priapism, or the development of scarring at the site of the injection. Alprostadil is now available in a gel and a patch. No long-term studies compare the efficacy and acceptance of these new forms of therapy with that of the oral agents.

Intraurethral therapy (MUSE)

Alprostadil, PGE1, has been formulated into a small suppository that can be inserted into the urethra. In a selected group of men, the agent was effective in 65%. This agent may be effective in men with vascular disease, diabetes, and status post prostate surgery. This is a useful agent for men who do not want to use self-injections or for men in whom oral medications have failed. It has been successfully used together with sildenafil in cases in which each agent alone failed. Few adverse effects occur, and the most common is a painful erection and urethral burning, which occurs in less than 10% of the patients.

Table 1. Types of Medical Therapy Available to Manage ED

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*Monoamine oxidase inhibitors

†US Food and Drug Administration

A comparison of satisfaction rates and ED in subjects treated with sildenafil, intracavernous PGE1 (alprostadil), and penile implant surgery was performed by Rajpurkar and Dhabuwala in 138 men with ED. This was a nonrandomized study in which all subjects were initially offered sildenafil. The mean follow-up was 19.54 months, and questionnaires were used to obtain the data. Their conclusions were that men with a penile implant had significantly better erectile function and satisfaction.

The development of future medical options will emphasize the restoration of physiologic function. A better understanding of the molecular biology of ED will allow the development of new classes of agents. Research involving gene therapy is beginning to show promise.

One such research area has involved the use of the angiogenic growth factor and endothelial cell mitogen, vascular endothelial growth factor (VEGF). This is produced by vascular smooth muscle, endothelial, and inflammatory cells. VEGF increases the production of nitric oxide, which improves endothelial function and blood flow in chronic ischemic disorders.

The direct intracavernosal injection of recombinant VEGF protein or adenoviral VEGF that contains plasmids have shown dramatic results based on cavernosography findings in animal models with arteriogenic, venogenic, and neural forms of ED. Burchardt et al identified VEGF 165 as the predominant isoform of the corpora cavernosa, as well as a novel splice variant.⁷ Although VEGF is a potent and important vascular regulator, it probably acts together with other vascular factors. Although a single-agent VEGF is unlikely to ever be used as monotherapy for ED, this represents an important step in understanding the normal and abnormal vascular physiology associated with ED.

Surgical Care

A small number of healthy young men have developed ED as a result of trauma to the pelvic arteries. Revascularization procedures such as rotating the epigastric artery, or even smaller vessels, into the corpora have been attempted. The long-term results have been marginal.

Men who have difficulty maintaining erections as a result of venous leaks occasionally may benefit from a surgical procedure to eliminate much of the venous outflow. While initial enthusiasm for this and other surgical approaches was significant, this type of surgery has become rare because of a lack of long-term efficacy.

Penile implants

In the past, the placement of prosthetic devices within the corpora was the only effective therapy for men with organic ED. Now, this is the last option considered, even though more than 90% of men with an implant would recommend the procedure to their friends and relatives.

Implants are usually used for men in whom other therapies have failed or in those who require penile reconstructions. Men who have had a radical prostatectomy for prostate cancer and in whom a nerve-sparing procedure was not performed or was not successful often do not respond to oral PDE-5 inhibitors, and these men are good candidates for an implant. The same is true for men treated with radiation therapy, although more of these men tend to respond to oral agents. Additionally, some patients experience increased sexual satisfaction with the combined use of an implant and an oral PD5 inhibitor.

Before selecting this form of management, the patient and his sexual partner should be counseled regarding the benefits and risks of this procedure.

Two types of devices are available, a semirigid and a multicomponent inflatable system. With the semirigid prosthesis, two matching cylinders are implanted into the corpora cavernosa. These devices provide enough rigidity for penetration and rarely break. The major drawbacks are the cosmetic appearance of the penis, which remains semi-erect at all times, the need for surgery, and the destruction of the natural erectile mechanism when the prosthesis is implanted.

The inflatable devices consist of two Silastic or Bioflex cylinders inserted into the corpora cavernosa, a pump placed in the scrotum to inflate the cylinders, and a reservoir that is contained either within the cylinders or in a separate reservoir placed beneath the fascia of the lower abdomen. The inflatable prosthesis generally remains functional for 7-10 years before a replacement may be necessary. Improvements in these devices have resulted in a failure rate of less than 10%. Complications include infections in 2% of patients, erosion of the device through the urethra or skin in 2% of patients, and painful erections in 1% of patients. A newer antibiotic-coated device has further reduced the infection rate.

Patient acceptance of these devices is very high, with nearly 100% of the patients expressing satisfaction. Part of this enthusiasm is related to the failure of other therapies and the highly motivated patient population.

Table 2. Types of Surgical Therapies for ED

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Consultations

Therapeutic options in managing erectile dysfunction

Currently, any man who wishes to have erectile function can do so regardless of the etiology of the problem. Many therapeutic options are available, and the task of the physician is to help the patient seek the best solution. Finding a trained and understanding physician who is willing to take the time to understand the patient's problem is the first step in identifying which therapeutic option will ultimately be most appropriate and successful.

Sexual counseling is the most important part of the treatment for patients with sexual problems. Many professional sexual counselors are skilled in working with patients, but the primary care physician, the urologist, and the gynecologist also serve in this capacity to some degree. These are usually the first professionals to learn about the problem, and they often have to extract the information about the sexual problem from the patient.

Men are frequently reluctant to discuss their sexual problems and need to be specifically asked. Opening a dialogue allows the clinician to begin the investigation or refer the patient to a consultant. Regardless of any subsequent therapy the patient may receive, the emotional aspects of the disorder must be addressed. Ideally, the couple should be involved in the counseling, but, even when this is not possible, the time spent may help resolve or at least clarify the problem certainly helps in deciding which of the other options would be most beneficial and appropriate.

Psychological care

Regardless of the etiology of ED, a psychological component is almost always associated with this disorder. The ability to achieve erection is intimately connected to a man's self-esteem and sense of worth. Pure psychogenic ED is generally evident when a man reports that he has normal erections some of the time but is unable to achieve or to maintain a full erection at other times. Once the man has doubt regarding sexual performance, he loses confidence; thus, future attempts to have sexual relations provoke anxiety. These men are desperate for help and depend on the physician's advice. In many instances, the couple needs to work together to resolve the problem, although the relationship may be responsible for the problem. Most physicians do not have the time to work with these patients and, instead, refer them to a sexual counselor.

Men with organic ED can be treated with one or more of the various available therapies. However, if they have lost confidence in their ability to obtain and maintain an erection suitable for penetration, a few words of encouragement from their physician can be of great help.

Medication

An increasing array of medications is available to assist in the management of erectile dysfunction (ED). New agents are still undergoing clinical testing, and more are in the early phases of development.

For any medication to be effective, the physiologic components involved in the erectile process must be functional. Serious impairments render the medication either completely or partially ineffective.

An ideal agent should be rapidly effective, easy to administer, affordable, applicable to a wide range of patients, and minimally toxic.

The types of medications can be divided into oral, topical, injectable, and intraurethral insertion.

Oral medications include neuropharmacologic agents that are adrenergic receptor antagonists (eg, phentolamine, yohimbine, delequamine), dopamine receptor antagonists (eg, apomorphine, bromocriptine), serotoninergic receptor activators (eg, trazodone), oxytocinergic receptor stimulators (eg, oxytocin), androgens, and PDE inhibitors.

Phosphodiesterase inhibitors

Oral agents that act peripherally to induce smooth muscle relaxation of the corpora cavernosa. The most commonly used agents are sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Sildenafil was the first in this series of PDE inhibitors. These agents rely on the role of NO in inducing vasodilatation. NO relaxes smooth muscle by stimulating guanylyl cyclase activity, which raises the intracellular concentrations of the cyclic nucleotide cGMP, which, in turn, induces vasodilation.

Intracellular cGMP is hydrolyzed by PDEs, terminating their action. PDEs are a diverse family of enzymes with different tissue distributions and functions, but all exert their effect by lowering intracellular cyclic nucleotide levels.

At least 7 PDE classes are known, many with subtypes identified by structure and function. PDE-5 is cGMP-specific and is a major cGMP-hydrolyzing enzyme in the vascular smooth muscle of the penis. The newer agents, vardenafil and tadalafil, are more specific and potent cGMP inhibitors than sildenafil. Both of the newest agents are PDE-5 inhibitors, which are significantly more selective in their inhibition.

In a 2009 randomized, multicenter, double-blind, placebo-controlled, crossover study of 191 men with ED (40% with baseline moderate ED and 33% with severe ED; the ENDURANCE study), Rosenberg et al found that vardenafil (10 mg) was superior to placebo.⁸

Sildenafil (Viagra)

PDE-5 selective inhibitor. Inhibition of PDE-5 increases cGMP activity, which increases vasodilatory effects of NO. Effective in men with mild-to-moderate ED. Take on an empty stomach approximately 1 h before sexual activity. Sexual stimulation is necessary to activate response. The increased sensitivity for erections may last 24 h. Available as 25-, 50-, and 100-mg tablets. Onset of action varies from 15-60 min, with a duration of action of 4-6 h. Half-life is 4-5 h.

Vardenafil (Levitra)

PDE-5 selective inhibitor. Inhibition of PDE-5 increases cGMP activity, which increases vasodilatory effects of NO. Effective in men with mild-to-moderate ED. Take on empty stomach approximately 1 h before sexual activity. Sexual stimulation is necessary to activate response. Increased sensitivity for erections may last 24 h. Available as 2.5-, 5-, 10-, and 20-mg tablets. Acts within 15-30 min and can be taken with food, although a high-fat meal can inhibit absorption. Half-life is 4.8-6 h.

Tadalafil (Cialis)

Novel PDE-5 selective inhibitor chemically unrelated to sildenafil and vardenafil. Effective for mild, moderate, and severe ED of varying etiologies, including both organic and psychogenic causes.
PDE-5 inhibition increases cGMP activity, which increases vasodilatory effects of NO. Sexual stimulation is necessary to activate response. Because sexual stimulation is required to initiate local release of NO, tadalafil has no effect in absence of sexual stimulation. Increased sensitivity for erections may last 36 h with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (ie, twice weekly); men can attempt sexual activity at anytime between daily doses. Available as 2.5-, 5-, 10-, and 20-mg tabs.
The major difference between tadalafil and the other PDE-5 inhibitors is its prolonged half-life of 17.5-21 h compared with sildenafil (4-5 h) and vardenafil (4.8-6 h). In those who respond, coitus has been recorded from 30 min to 36 h after administration.
Using validated sexual questionnaires (ie, SEP-2, SEP-3), Brock et al reported that 75% of male subjects taking 20 mg were able to complete intercourse, compared with 38% of those taking placebo. Using the IIEF questionnaire, 59% of subjects were able to return to normal sexual function, compared with 11% of the control subjects.

Injectables

Agents that are injected directly into the penis exert their relaxant effect directly on the corpora cavernosal smooth muscle. They can be used as single agents or in combination. The most commonly used agents include PGE1, papaverine, and phentolamine. The dose and most effective combination of these agents must be determined for each patient. These medications can be obtained commercially as Caverject (PGE1) or can be formulated according to the physician's request by compounding pharmacies. Patients can be supplied with vials of a single agent or a combination of agents mixed in a single vial. Patients must be instructed in the proper technique for administration. A single intraurethral agent, PGE1, which has been formulated into a small suppository, is commercially available as MUSE. This agent was available prior to the introduction of sildenafil and is still used by a select group of men.

Alprostadil (Caverject Injection, Edex Injection, MUSE Pellet)

Identical to naturally occurring PGE1 and has various pharmacologic effects, including vasodilation and inhibition of platelet aggregation. When injected into the penile shaft, it relaxes trabecular smooth muscle, dilating cavernosal arteries, which, in, turn promotes blood flow and entrapment in the lacunar spaces of the penis, causing penile erection. Various doses have been used.
Commercially, Caverject is available in doses of 10-20 mcg, but a number of pharmacists and physicians prepare PGE1 in doses appropriate to the individual patient.

Papaverine (Pavabid, Pavatine)

Benzylisoquinoline derivative with direct nonspecific relaxant effect on vascular, cardiac, and other smooth muscle.

Phentolamine (Regitine)

Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on the alpha-receptors.

Alprostadil (Alprox TD)

Cream applied to the glans penis is most effective in men with mild-to-moderate ED. Effect is noticeable within 5 min. Same medication used for injection therapy and in MUSE system.
Cream has been tested in 1700 male subjects with mild-to-severe ED. Three different dosing levels showed statistical improvement compared with placebo. Can be used by patients taking nitrates and alpha-blockers.
Adverse effects are limited to application site and are mild-to-moderate in severity. Stinging at urethral meatus was the most prevalent adverse effect. No serious adverse effects were reported. Discontinuance rate due to adverse effects is 3%.

Androgens

Primarily of benefit for men with low levels of serum testosterone. Men who are hypogonadic, who desire a restoration of libido, and who wish to become sexually active usually benefit from the exogenous supplementation of androgens. This can be accomplished with injections, cutaneous application via gel or skin patches, or oral administration.

Testosterone (Androgel, Testoderm, Depo-Testosterone)

Promotes and maintains secondary sex characteristics in androgen-deficient males. Depot injections can produce high levels of serum testosterone when administered in adequate doses.

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