Lack of penile erections

Management of erectile dysfunction is focused at lifestyle changes and management of current medications.

Smoking cessation, managing diabetes, decreasing cholesterol, and treating hypertension may improve erectile function and facilitate medical treatment. Please note this is not a page about the treatment of premature ejaculation, however it is often useful to bear in mind the possibility of PE and ED occurring together: erectile failure often causes premature ejaculation, though rarely, in my experience, does this association develop in the reverse order.

Modifying antihypertensive medications to include erection hospitable agents such as ACE inhibitors, calcium channel blockers, and ARBs may maintain control of hypertension with restoration and maintenance of erectile function. Patients with low testosterone should receive injectable or topical testosterone supplements. If depression or relationship issues are significant problems, sexual counseling or psychiatric therapy may be helpful in addition to pharmacologic treatment.

Office counseling with patient and partner may facilitate understanding and probable causes of the ED treatment alternatives, and expectations. Indeed, recent evidence has supported improvement of erectile function with sexual counseling.

First-line therapy for regaining erections in the penis

If lifestyle changes and medication modifications fail to improve erectile function, safe, effective oral agents are available for the treatment of ED. The introduction of sildenafil in 1998 revolutionalized the treatment of erectile dysfunction by providing an effective, safe method for restoring erectile function with minimal side effects and adverse events.

Sildenafil as well as tadalafil and vardenafil are selective PDE-5 inhibitors that facilitate cGMP and subsequent corpus cavernosal smooth muscle relaxation. Improvement in erectile function occurs as quickly as 15 minutes after a dose and is maximum at 60 minutes following ingestion of sildenafil and vardenafil.

Tadalafil, a longer-acting agent is active longer than the 4 hours for sildenafil and vardenafil with a half life of 17.5 hours.

Sildenafil, now has five years of clinical experience and is usually begun at 50 mg although for most patients doses of 100 mg are required for satisfactory results.

First and second doses may not be effective as multiple doses and studies have demonstrated that as many as eight trials may be necessary for full success and effectiveness. Adverse events include headache, dyspepsia, facial flushing, blue vision and rhinitis.

In subgroup studies, sildenafil has been reported to significantly improve erectile function compared with placebo in patients with both type 1 and type 2 diabetes with and without complications, spinal cord injury, hypercholesterolemia, depression, hypertension, cardiac disease, and patients following radical prostatectomy.

In patients with psychogenic ED also the results are excellent. While sildenafil is effective for ED of virtually all types of etiology and severity, it is least effective in patients with severe vascular disease as are all oral agents.

Tadalafil and vardenafil, while recently introduced, have fewer published clinical and basic science studies to document effectiveness and tolerability. The data available, however, demonstrate excellent effectiveness in similar subgroups of patients as sildenafil.

Side effects are similar, but blue vision is reduced with both newer agents. Tadalafil, however, appears to cause less rhinitis but back pain in some selected patients.

All three PDE-5 inhibiting agents are safe and effective in all groups of patients except those having vascular disease. In these patients, the additive blood pressure lowering effects may produce profound hypotension.

Additionally, care must be taken in co-administering et-blocking agents since some select groups of patients may report dizziness and hypotension.

Other oral agents have previously been used with some limited success. Prior to the introduction of sildenafil, yohimbine, a presynaptic blocking agent was widely used as an oral agent.

This medication, which often produces erectile function especially in combination with other erectogenic agents, has demonstrated minimal improvement in placebo controlled trials. Its side effect of significant hypertension limits its use to patients with cardiovascular disease. Trazodone a non-SSRI antidepressant has also been used for treatment of ED. Because of its side effect of priapism in some patients being treated for depression, it has been tried as an oral agent for ED but only with limited success.

Central nervous system acting agents are available and in development. Apomorphine has been approved in Europe as an oral treatment of ED. This non-opiate dopamine agonist has its predominant effects in the hypothalamus. The sublingual preparation currently used produced erectile function within 30 minutes of administration in both double-blind placebo controlled studies and postmarketing reports.

Its effectiveness, while less than PDE-S inhibitors is significantly better than placebo with side effects including nausea, vomiting, and in a small minority of patients, syncope.

The success of this agent has spurred investigation of other agents for the treatment of ED. Melanotan or melatonin stimulating hormone (MSH) has also been demonstrated to be effective in selected patients with both organic and psychogenic ED.

Second-line therapy for penile erectile capability

In patients in whom first-line therapy with oral agents or changes in lifestyle fail to improve erectile function and who are motivated to continue with therapeutic alternatives, second-line therapy is available. This includes intracavernosal injection therapy, vacuum erection device therapy and intraurethral and topical medication administration.

1980s using phenoxybenzamine with improvement in erectile function in both organically and psychogenically impotent men. Subsequent development of combination therapy with PGE1, phentolamine, and papaverine have increased the effectiveness, comfort and safety of injection therapy.

Currently PGE1 or alprostadil is administered at doses of 2.5-5 mg. Patients with significant vasculogenic ED require higher starting and maintenance doses. After an initial in-office titration to a dose that produces a firm erection satisfactory for sexual intercourse that lasts no longer than 60 minutes many men may require at-home dosage adjustment. If erections persist for more than 4 hours, patients should be advised to go to the emergency room for treatment with an otagonist such as intracavernosal phenylephrine or aspiration therapy.

While this complication is rare, early treatment will preserve future erectile function and allow patients to continue with injection therapy.

If initial treatment with intracavernosal PGE1 is ineffective or produces excessive penile pain, pain, combination of papaverine with or without phentolamine and PGE1 may produce satisfactory erectile function with less penile discomfort.

Side effects from this combination are similar to PGE1 alone and include prolonged erections, priapism, corpus cavernosum fibrosus, and occasional transient hypotension.

The most common adverse event, however, is penile pain most commonly seen with PGE1.

This complication occurs after approximately 20% of injections. Other complications such as hematoma, edema and corpus cavernosum fibrosus occur in less than 5% of patients. Despite initial success rates in excess of 70% with these injection techniques, few patients continue injection therapy for more than 3-4 years? The reasons for discontinuation include inadequate erectile function, penile pain, poor patient partner satisfaction and anxiety. Several series have reported less than 50% continuation rate at 60 months.

Other alternatives include topical or transurethral PGE1 (alprostadil). The transurethral system, medicated urethral system for erection (MUSE), is available in 250, 500 or 1000 mg strength. Its effectiveness is approximately 30% in large clinical studies.

A small applicator with a pellet of PGE1 is placed approximately 2 cm in the urethra. After the pellet is deposited and the applicator removed the patient stimulates the urethra to allow PGE1 to enter the corpus cavernosa. Erection occurs within 10-15 minutes and is maintained for as long as 40 minutes.

Rare side effects include prolonged erection, priapism, but significant penile pain, aching, and urethral burning can occur. While this agent is an excellent addition to patients with penile prosthesis for further engorgement and is useful as combination therapy with PDE-5 oral agents, its success as a single agent in patients with severe ED has been disappointing. Newer formulations using a topical administration of PGE1 have completed clinical trials with success greater than that of MUSE and with similar adverse events.

The agents may be useful in some patients as primary therapy or in future helpful as combination treatment. These alternatives while less effective than direct injection eliminate the need for needles and injections into the penis.


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