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Erectile Dysfunction: Treatment of Impotence

• Erectile Dysfunction: Epidemiology and causes
• Erectile Dysfunction: Signs, symptoms and diagnostic workup
• Erectile Dysfunction: Medical and surgical treatment

Review literature: (Lue, 2000) (Porst, 2004).

Medical and Conservative Treatment of Erectile Dysfunction

Lifestyle Changes

The renunciation of smoking, regular exercise, only moderate amounts of alcohol and a healthy diet can prevent the development of erectile dysfunction. A change in lifestyle in midlife with manifest erectile dysfunction is, however, often too late and has little therapeutic value in regard of erectile function within months. If a change in lifestyle is maintained over years, vascular changes are partly reversible and erectile dysfunction may improve in 30% of men (Esposito et al., 2004). Advanced vascular changes are not reversible. However, lifestyle modification should in principle be recommended to all patients with ED, as it increases the efficacy of oral medications and improves cardiovascular prognosis (Meldrum et al., 2011). Improvement in erectile dysfunction can also be expected in alcoholics with abstinence. The change of a medication with side effects on erectile function is a good option for improvement of ED, if the cardiological or neurological safety is maintained.

Physiotherapy

Physiotherapy (pelvic floor exercises) may show a therapeutic effect in erectile dysfunction due to mild venous insufficiency.

Late-onset Hypogonadism

Testosterone substitution should be considered for patients with late-onset hypogonadism (LOH) and erectile dysfunction. The effect of testosterone substitution on erectile function is only moderate, but improved libido and better effectiveness of oral drugs can be expected. LOH is frequently associated with a metabolic syndrome, testosterone substitution improves several parameters of the metabolic syndrome. Whether a long-term androgen therapy shows a benefit for the patients in regard of overall survival remains to be proven. Over the long term, risks of testosterone supplementation is poorly understood.

Other drugs as L-carnitine or DHEA are also used in the treatment of erectile dysfunction with symptoms of ADAM, however, there are no supporting controlled trials.

Phosphodiesterase type 5 (PDE5) Inhibitors

Phosphodiesterase type 5 (PDE5) inhibitors have simplified the treatment of erectile dysfunction. PDE5 inhibitors offer, compared to other orally active drug, a superior efficacy. The success rates of PDE5 inhibitors (successful sexual intercourse) is around 70-75% in patients with ED and with maximal dosage. The market share of new PDE5 inhibitors (vardenafil, tadalafil) is increasing to the expense of sildenafil. Tadalafil has a longer mechanism of action and is marketed as "weekend pill". Vardenafil has a faster onset of action and a favorable side-effect spectrum. General mechanisms of action, side effects and pharmacokinetics see section phosphodiesterase type 5 inhibitors. Dosage of PDE5 inhibitors:

• Sildenafil: dosage 25 mg, 50 mg and 100 mg. Onset of action: 30–60 min. Duration 4–6 h.
• Vardenafil: dosage 10 mg and 20 mg. Onset of action: 30–60 min. Duration 4–8 h.
• Tadalafil: dosage 10 mg and 20 mg. Onset of action 60–120 min. Duration 12–36 h

Other Drugs used against Erectile Dysfunction

Due to the efficiency of PDE5 inhibitors, drugs listed below have a minor role in treating erectile dysfunction.

Treatment of Hyperprolactinemia

Hyperprolactinemia is treated with oral dopamine agonists like cabergoline or bromocriptin.

Yohimbine:

Yohimbine is a competitive α-adrenergic antagonist with effect on the CNS. Yohimbine promotes erection by central mechanisms. Yohimbin has only effect in patients with psychologic or minor organic erectile dysfunction, since for the mechanims of action an organically intact erectile tissue and innervation is necessary. Dosage: 3 days starting on 3 × 5 mg p.o., afterward 3 × 10 mg p.o.

Side effects of yohimbine: gastrointestinal symptoms, palpitations, headache, agitation, anxiety, hypertension (Cave: cardiovascular diseases).

Apomorphine:

Apomorphine is a dopaminergic agonist who activates D1 and D2 receptors in the hypothalamus (paraventricular nucleus, medial area praeoptica ...), a center of sexual desire. Apomorphine shows a dose-dependent effect: 2 mg vs. Placebo (46% vs. 32%), 4 mg vs. Placebo (52% vs. 35%) and 6 mg vs. Placebo (60% vs. 34%). However, this applies also nausea, the main side effect: 2%, 22% and 41% for 2, 4 and 6 mg. Other side effects: dizziness, vomiting, sweating, fatigue, syncope (very rare).

Apomorphine can be administered sublingually. An indication for apomorphine are patients with contraindications to PDE5 inhibitors (e.g., nitrate therapy).

Trazodone

Trazodone ist a non-tricyclic antidepressant with erection-promoting effects, but not approved for ED therapy. Trazodone is a treatment option in patients with depression and ED, dosage 50–150 mg/d.

Topical treatment:

Ointments with vasoactive ingredients such as alprostadil are approved and available on the market. Local side effects for patient and partner, the difficult transdermal absorption and thus the moderate clinical effect are known disadvantages (Rooney u.a., 2009).

Effective natural products:

Butea superba, Korean Ginseng.

Treatment of Erectile Dysfunction with Intracavernosal Injections and Devices

Intracavernosal Injection Therapy

The indications for intracavernosal injections (ICI) are patients with poor efficacy of oral therapy or contraindications to PDE5 inhibitors. In diagnostic ICI, the dose of alprostadil (prostaglandin E₁) is determined, which usually lies between 5 and 20 mg alprostadil. After instruction of the patient in the technique of ICI, success rates of 94% have been reported.

Side effects of intracavernosal injections: painful injection, which can be avoided by slow injection. 5% prolonged erection, 1% risk of priapism. Fibrosis of the erectile tissue 2%. hematoma 8% .

If ICI with alprostadil shows no or not enough response, intracavernosal injections are possible with papaverine (opium alkaloid) and/or phentolamine (α-blocker). Either can be given alone or in combination, the side effect spectrum is considerably higher.

Transurethral administration of Alprostadil (MUSE)

Transurethral administration of alprostadil in form of a gel is an effective treatment option, which is helpful in patients with fear of intracavernosal injections. The abbreviation MUSE stands for Medicated Urethral System for Erection. The effectiveness is controversial.

Vacuum Erection Device

Vacuum therapy uses a plastic cylinder, which is placed over the penis and sealed at the base. By creating a vacuum with a hand pump, the penis is filled passively with blood until an erection is reached. After removal of the cylinder, the erection is maintained with the help of a penis ring at the base of the penis.

There is good objective success rate of vacuum therapy, which can be improved with the combination of vacuum therapy with intracavernosal injections or PDE5 inhibitors. The high rate of side effects (pain, difficult ejaculation, ecchymosis) and the availability of effective alternative lead to an acceptance rate of only 30–70%.

Extracorporal shock wave therapy:

Low intensity ESWT of the penis has recently emerged as a novel therapeutic option. ESWT stimulates cell proliferation, angiogenesis, and regeneration of erectile tissue leading to a possible long-term effect. Several smaller comparative studies showed an improvement of erectile function in terms of IEFF and erection hardness score with response rates around 60–80%, even in men who no longer responded to PDE5 inhibitors (Sokolakis et al., 2019a). Until publication of larger randomized trials with long follow-up are available, no clear recommendation can yet be made.

Surgical Therapy of Erectile Dysfunction

Penile venous ligation:

Penile venous ligation is an option for isolated venous insufficiency in young patients and proven arterial sufficiency. The diagnostic workup should include intracavernosal injection with duplex ultrasonography and dynamic infusion cavernosometry and cavernosography (DICC). Isolated corporal veno-occlusive dysfunction may be seen in dorsal penile veins or crural veins, which can be accessed through various approaches. However, moderate to disappointing results are published in the long-term, very careful individual patient selection and education is advised (Sohn et al., 2013).

Penile Arterial Revascularization:

Although arterial insufficiency is a frequent cause of ED, interventional procedures or vascular surgery did not prove successful in therapy, this is especially true for older patients with peripheral arterial disease, long smoking history and diabetes mellitus. Successful concepts for revascularization exist in young men (without PAD) e.g., after pelvic trauma (Babaei et al., 2009). Angiography is necessary for treatment planning (see above). Venous insufficiency should be excluded before revascularization. Proximal stenoses of the internal iliac artery can be treated by PTA (percutaneous transluminal angioplasty). Different surgical procedures exist for distal arterial stenoses; all use the inferior epigastric artery as the donor artery. Common complications include thrombosis of the anastomosis, glans hyperemia, and inconsistent long-term outcomes (30--80% success). Because of the infrequent indication and sometimes poor long-term results, the operations listed below are performed only occasionally:

• Side-to-end anastomosis of the inferior epigastric artery with the dorsal penile artery.
• Side-to-end anastomosis of the inferior epigastric artery with the vena dorsalis penis, which is ligated proximally and distally (Furlow-Fischer technique).
• Anastomosis of the inferior epigastric artery simultaneously with the dorsal penile artery and vein (AV-fistula). The high blood flow in the AV-fistula reduces the risk for thrombosis (Hauri technique).
• Direct anastomosis of the inferior epigastric artery with the corpus cavernosum. This leads to a high risk of anastomosis thrombosis and is not performed any more.

Penile Implants

Penile prothesis for treatment of erectile dysfunction are indicated after failure of intracavernosal injection or vacuum therapy in motivated patients. Patients have to be advised about the different prothesis systems including costs and technical differences, surgical risks (infection, perforation) and possible mechanical failure (Montague et al., 2011).

Malleable (semiregide) penile prosthesis:

Advantages of semirigid penile prosthesis are the easy implantation, low risk of mechanical failure and low costs. The disadvantage is the permanent semiregide erection, which can bother in everyday life.

Hydraulic penile implants:

The basic structure of the inflatable penile prosthesis is similar to an artificial urinary sphincter and consists of a three-piece construction: paired penile cylinders as implant for the corpus cavernosum, fluid reservoir and a scrotal pump (inflatable penile prothesis AMS 700). The advantage of inflatable prosthesis is the better functionality, disadvantages are the costs and the risk of mechanical failure.

Sexual therapy:

In 40% ED is based on a psychogenic cause, the younger the more frequent. The effectiveness of PDE5 inhibitors for psychogenic cause is high. Due to the frequency of the condition, no capacity exists to provide additional sex therapy or psychotherapy to all men with psychogenic ED; it should be made available to men with relevant psychiatric comorbidity.

References

Johannes u.a. 2000 JOHANNES, C. B. ; ARAUJO, A. B. ; FELDMAN, H. A. ; DERBY, C. A. ; KLEINMAN, K. P. ; MCKINLAY, J. B.: Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study.
In: J Urol
163 (2000), Nr. 2, S. 460–3

Lue 2000 LUE, T. F.: Erectile dysfunction.
In: N Engl J Med
342 (2000), Nr. 24, S. 1802–13

Porst 2004 PORST, H.: Tadalafil, Therapiestrategien bei erektiler Dysfunktion.
Linkenheim-Hochstetten : Aesopus Verlag, 2004

  Deutsche Version: Erektile Dysfunktion: Therapie