Dr. med. Dirk Manski

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Erectile Dysfunction: Treatment of Impotence

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 (ED). A change in lifestyle in midlife with manifest erectile dysfunction is, however, often too late and has little therapeutic value regarding erectile function within months. If a lifestyle change is maintained over the 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). Alcoholics can expect improvement in erectile dysfunction with abstinence. The change of medication with side effects on erectile function is a good option for improving ED if cardiological or neurological safety is maintained.

Physiotherapy

Physiotherapy (pelvic floor exercises) may show a therapeutic effect on erectile dysfunction by improving 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 metabolic syndrome, and testosterone substitution improves several parameters of the metabolic syndrome. Whether a long-term androgen therapy shows a benefit for the patients regarding overall survival remains to be proven. Over the long term, the risks of testosterone supplementation are poorly understood.

Other drugs, such as L-carnitine or DHEA, are also used in the treatment of erectile dysfunction with symptoms of LOH. 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 drugs per os, a superior efficacy. The success rate of PDE5 inhibitors (successful sexual intercourse) is around 70-75% in patients with ED and with maximal dosage. For mechanisms of action, side effects, and pharmacokinetics see section phosphodiesterase type 5 inhibitors. Dosage of PDE5 inhibitors:

Other Drugs used against Erectile Dysfunction

Due to the efficiency of PDE5 inhibitors, the 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 an effect on the CNS. Yohimbine promotes erection by central mechanisms. Yohimbine has only effect in patients with psychologic or minor organic erectile dysfunction since, for the mechanisms of action, organically intact erectile tissue and innervation are 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 that 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 to nausea, the main side effect: 2%, 22% and 41% for 2, 4 and 6 mg. Other side effects: dizziness, vomiting, sweating, fatigue, or syncope (exceptional). Apomorphine is administered sublingually. Apomorphine is an option in patients with contraindications to PDE5 inhibitors (e.g., nitrate therapy).

Trazodone

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

Topical treatment:

Ointments with vasoactive ingredients, such as alprostadil, are approved and available on the market. Local side effects for patients and partners, the difficult transdermal absorption, and 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. Diagnostic ICI is used to determine the correct individual dosage of alprostadil (prostaglandin E1), which usually lies between 5 and 20 mg alprostadil. After the patient's instruction in the ICI technique, success rates of 94% have been reported. If ICI with alprostadil shows no or not enough response, intracavernosal injections are possible with papaverine (opium alkaloid) and phentolamine (α-blocker). Either can be given alone or in combination, but the side effects (priapism) are considerably higher.

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%, and hematoma 8%.

Transurethral administration of Alprostadil (MUSE)

Transurethral administration of alprostadil as a gel or suppository is an effective treatment option, which is helpful in patients with a fear of intracavernosal injections. The brand MUSE stands for Medicated Urethral System for Erection. The effectiveness is lower than PDE5 inhibitors or intracavernosal injections.

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%.

Extracorporeal 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, with response rates around 60–80%, even in men who no longer responded to PDE5 inhibitors (Sokolakis et al., 2019a). Until the publication of larger randomized trials with long follow-ups is available, no clear recommendation can yet be made.

Autologous platelet-rich plasma (PRP):

PRP is obtained by plasmapheresis and injected into the corpus cavernosum in several sessions. PRP injections may be combined with ESWT. PRP is rich in growth factors, which are thought to stimulate neoangiogenesis and regeneration of endothelium and nerves. Initial placebo-controlled trials were effective (Poulios et al., 2021), but the procedure is still considered experimental.

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:

Penile Implants

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

Malleable (semirigid) penile prosthesis:

The advantages of semirigid penile prosthesis are 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 prosthesis 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.






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References

Braun u.a. 2000 BRAUN, M. ; WASSMER, G. ; KLOTZ, T. ; REIFENRATH, B. ; MATHERS, M. ; ENGELMANN, U.: Epidemiology of erectile dysfunction: results of the Cologne Male Survey.
In: Int J Impot Res
12 (2000), Nr. 6, S. 305–11

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