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The Princeton Consensus Conference was developed to stratify ED patients by cardiovascular status into low-, intermediate, and high-risk categories to assist practitioners in determining whether a particular patient can

safely

22 More recent postmarketing reports of decreased vision or complete loss of vision as a result of nonarteritic anterior ischemic optic neuropathy (NAION) have led to further investigation of a temporal relationship between the PDE 5 inhibitors and this condition. NAION is an uncommon visual disorder that can lead to decreased visual acuity as a result of a swollen or "crowded optic disc" and is

typically

22 Given that the risk factors for NAION share a close association with underlying disorders observed in ED patients receiving treatment with PDE 5 inhibitors, it remains unclear whether these agents increase the likelihood of developing NAION.

Prior to the market arrival of the oral PDE 5 inhibitors, alprostadil, a prostaglandin E 1 analog that facilitates the erectile response through cavernosal smooth muscle relaxation, was considered the treatment of choice for the management of ED. 12 Alprostadil remains the preferred second-line treatment option for patients who are unable to tolerate, or have an inadequate treatment response to the PDE 5 inhibitors.

14 Alprostadil is commercially available as Caverject Impulse and Edex intracavernous injections, as well as Muse urethral suppositories. At the time of this review, Caverject Impulse is temporarily unavailable through the drug manufacturer. Alprostadil, when administered via intracavernous injection, has a quick onset of action and typically results in an erection within 5 to 20 minutes.

23 Patients who are ideal candidates for intracavernous therapy should receive thorough education and training on proper self-injection technique. Initial dosing and titration is performed within the physician's office utilizing the lowest dose necessary to produce a 30 to 60 minute sildenafil dapoxetine tablets online erection sufficient for intercourse.

24 The initial recommended dose of intracavernous alprostadil is 2.5 µg and should be titrated in 5 to 10 µg increments until a response is observed. The average doses used in clinical studies ranged from 10 to 20 µg and the recommended injection frequency is no more than 3 times weekly. Alprostadil urethral suppositories are absorbed through the urethral lining within 10 minutes and have a duration of action of about 30 to 60 minutes.

25 Self administration of suppositories within the urethra can be challenging; patients should be closely supervised in the office setting during the initial treatment period. A low starting dose of 125 to 250 µg is recommended and may be titrated to 500 µg or 1,000 µg as tolerated.

Clinical studies evaluating the efficacy of alprostadil have generally found that the intracavernous injections are more effective than the urethral suppository formulations.

In a randomized, open-label, multicenter study involving 111 patients, 82.2% of intracavernous administrations resulted in successful intercourse, compared to 47.4% of urethral alprostadil suppository administrations ( P 28 Similar results were found in a study that compared intracavernous injection to urethral suppository use in 66 patients with ED. Of alprostadil injections, 85% led to intercourse, compared to only 55% of suppository administrations ( P 27. Both dosage formulations of alprostadil are administered locally and rapidly metabolized, making systemic side effects relatively uncommon with these agents. Local sildenafil dapoxetine tablets online side effects such as penile pain associated with injection and urethral burning are the most common treatment-associated complications, occurring with variable incidence but reported in 17% to 37% of patients in clinical studies.

23-25 Potentially serious side effects, such as prolonged erection and priapism are much less common and sildenafil dapoxetine tablets online have been reported in approximately 1% of patients using alprostadil formulations.

Intracavernous papaverine and phentolamine, like alprostadil, are smooth muscle relaxants that facilitate the erectile process through the dilation of cavernosal arteries.

Phentolamine lacks substantial effectiveness when used alone and papaverine monotherapy is associated with a higher incidence of prolonged erection and fibrosis so both drugs are typically combined and compounded at specialized pharmacies. 12 The resulting product is referred to as "bimix." Another formulation called "trimix" is prepared with the addition of alprostadil. In clinical studies evaluating the combined use of all 3 vasoactive agents, the success rate has been comparable to alprostadil monotherapy.

Therefore, the guidelines from AUA recommend that an initial trial of melrose pharmacy sildenafil alprostadil monotherapy be considered in patients who are candidates for vasoactive therapy.

12 For patients who fail alprostadil monotherapy, bimix and trimix formulations can be considered.

ED has been associated with low serum testosterone levels secondary to hormonal conditions such as hypogonadism, and testosterone replacement therapy has been shown to improve these symptoms in patients with androgen deficiency.

29 Several testosterone replacement products are commercially available including: immediate and delayed release injections, a transdermal patch, topical skin gels, a buccal mucosa delivery system, and sterile pellet implants. The less-practical, short-acting testosterone propionate injection is administered several times a week and has been largely replaced by the lipid soluble ester formulations, testosterone cypionate and enanthate, which can be administered every 2 to 4 weeks. Two transdermal formulation patches (Testoderm and Testoderm TTS) designed for application to the scrotum are both currently unavailable through the drug manufacturer. One available non-scrotal transdermal delivery system (Androderm) is available in 2.5 mg and 5 mg systems, which should be reapplied nightly, every 24 hours.

A 1% testosterone gel preparation (AndroGel) for trandermal delivery is available in 2.5 g and 5 g unit dose packets.

A metered dose pump (Testim) is another 1% testosterone gel and is available in 5 g tubes.

Patients should be instructed to wash hands after applying and avoid showering within 2 hours of application. A controlled-release mucoadhesive buccal delivery system (Striant) is designed to administer 30 mg of testosterone over a 12-hour period when applied above the incisor tooth twice daily.

Implantable sterile cylindrical pellets (Testopel) are subcutaneously implanted by a healthcare professional and continuously deliver testosterone for 3 to 4 months or up to 6 months. Dosage should be individualized based on the minimum daily requirements of testosterone; two 75 mg pellets should be implanted for each 25 mg testosterone propionate required weekly.

Testosterone replacement therapy for the treatment of ED is controversial due to the lack of substantial data supporting the benefit of this treatment modality and the potential risk of long term side effects. A meta analysis found a significant mean erectile response rate in men with hypogonadism on testosterone therapy compared to placebo (65.4% vs 16.7%, P 30 However, a recent review found an inconsistent and non-significant effect on erectile function in patients with low testosterone (effect size, 0.80; 95% CI, -0.10-1.60).

31 Testosterone treatment is generally well tolerated, with dermatologic reactions during transdermal replacement therapy being the most common side effects.

The risks of developing prostate cancer while on long-term testosterone therapy have not been fully established, so close PSA monitoring is necessary.

Vacuum Erection Devices (VEDs) are appealing nonpharmacologic options for patients because their efficacy is comparable to the PDE 5 inhibitors and they are associated with a relatively high margin of safety when used correctly.