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Erectile Dysfunction

Essentials

  • If a patient brings up erectile dysfunction (ED) at a doctor's office, the symptom must be significant for him.
  • A sexual history will help to find out the underlying cause.
  • ED is often of organic origin. Psychological problems and any problems associated with the couple relationship aggravate ED.
  • Any underlying organic or lifestyle problems should be identified and treated, as far as possible.
    • ED may be the first sign of a cardiovascular disease.
  • Primary ED in a young man has to be investigated by a urologist. An older man with ED that has developed gradually can be treated by a general practitioner.

Definition and prevalence

  • Erectile dysfunction is defined as inability to achieve and maintain a penile erection that is sufficient for satisfactory sexual performance.
    • There may be difficulty achieving an erection or the erection may be lost during intercourse.
  • ED may be permanent or intermittent, and it may be mild, moderately severe or severe.
  • ED is a common symptom affecting quality of life and any couple relationship.
  • Its prevalence increases with age, being about 10%, 35% and >50% in men below 40, 40 to 70 and over 70, respectively.

Aetiology

  • Vascular diseases (the most common cause)
    • Cardiovascular diseases: hypertension, coronary artery disease, cerebrovascular disorders, peripheral artery disease, type 1 or 2 diabetes, hyperlipidaemia
  • Neurogenic causes and sleep apnoea
    • Diabetic neuropathy, alcohol neuropathy, autonomic neuropathy, multiple sclerosis
    • Trauma or operations in the pelvic area (prostatic surgery!)
    • Long distance cycling
  • Hormonal and endocrine causes
    • Hypo- or hyperthyroidism
    • Hypogonadism, testosterone deficiency
    • Hyperprolactinaemia
  • Psychological causes
    • Mental disorders
    • Problems in the couple relationship and other psychosocial problems
  • Prostate diseases, penile anomalies, Peyronie's disease
  • Lifestyle
    • Smoking, alcohol, illegal drugs, anabolic steroids
      • Smoking at least doubles the risk of ED.
    • Physical inactivity, overweight
      • BMI > 30 kg/m2 increases the risk 3-fold.
    • Adverse drug effects
      • Thiazide diuretics, beta blockers, antidepressants (SSRI, tricyclic antidepressants) antipsychotics, antiandrogens, for example

Investigations

General and sexual history

  • See Figure 1 in http://d56bochluxqnz.cloudfront.net/media/EAU-Guidelines-on-Male-Sexual-Dysfunction-2018-large-text.pdf.
  • Time of onset: did the patient always have this problem or did it begin later?
    • In the latter case, find out the circumstances in which it began (such as trauma, new partner, falling ill, stress).
  • Is there loss of erection when putting on a condom, on penetration or during intercourse?
  • Is ED an independent problem or a consequence of some other sexual disorder (such as the partner's lack of sexual desire or dyspareunia, premature ejaculation)?
  • Is the problem generalized or specific for a certain situation?
    • A situation-specific problem suggests psychogenic causes.
  • Is the patient's life stressful (work, daily life in a family with children, financial problems)?
  • If he is in a couple relationship, how is the relationship?
  • Find out whether masturbation is successful and whether there are morning erections.
    • Normal masturbation suggests a psychogenic cause.
    • Lack of morning erections suggests an organic cause.
  • Is the quality and quantity of sexual stimulation sufficient? Is the context of sexual activity erotic?
  • Level of sexual activity and how satisfactory it was before the onset of ED
  • Any history of traumatic or distressing experiences, such as sexual abuse, violence, infidelity in a couple relationship, beliefs, cultural factors
  • Performance anxiety is usually involved.
    • The history usually gives an idea of whether this is an organic, psychogenic or mixed type of problem or associated with the couple relationship.
    • In most cases, there is an underlying organic problem which is nearly always aggravated with time by performance anxiety and sometimes by conflicts in the couple relationship.

Clinical status

  • Blood pressure, circulation (femoral and peripheral arterial pulses)
  • Thyroid
  • Tendon reflexes
  • Prostate
  • Penis (Peyronie's disease)
  • Any signs of hypogonadism; size and consistency of the testes, body hair, gynaecomastia etc.

Laboratory tests

  • At the first visit
    • HbA1c or plasma glucose, lipids, basic blood count with platelet count, serum testosterone
  • At follow-up visits, as necessary
    • Serum testosterone (if the testosterone concentration at the first visit was below 12.1 nmol/l), SHBG and, based on these, calculated free testosterone, LH, prolactin, and PSA
  • See also article Male hypogonadism Male Hypogonadism and Hormone Replacement.

Treatment Group Psychotherapy for Erectile Dysfunction

Lifestyle and underlying diseases

  • Image 2
  • Lifestyle interventions
    • Smoking cessation
    • Weight loss
    • Increasing physical activity
      • Physical activity reduces the risk of ED by 40-60%.
    • Stress management and a healthy couple relationship are important.
    • Heavy alcohol consumption may increase the risk of ED by lowering testosterone levels, for example.
  • Treatment of underlying disease contributing to the ED
    • Diabetes and hypertension, in particular, should be brought under control as far as possible.
  • Medication affecting erectile function should be changed, as far as possible.
    • ARBs are not harmful; they may even be beneficial.
    • The effects of calcium channel blockers and ACE inhibitors are neutral.
    • Beta blockers may be detrimental but the effect of nebivolol is neutral.
    • Thiazide diuretics and spironolactone are associated with an increased risk of ED.
    • Of antidepressants, moclobemide, bupropion, trazodone and vortioxetine are generally safe.

Specific medication

  • Image 3
  • Drug therapy is usually started at the same time as motivating the patient to modify their lifestyle.
  • Treatment can be pharmacological and/or surgical and is divided into three levels.

Phosphodiesterase type-5 (PDE5) inhibitors

  • All these drugs require sexual arousal. Their mechanism of action is based on a relaxing effect on the smooth muscle of penile arteries mediated by nitric oxide.
  • Their use can perfectly well be started in primary health care.
  • Each drug should be tried 4-8 times before definitely deciding that it is ineffective.
  • There are no big differences in the efficacy of the drugs. They help significantly about 75% of men.
  • The effect of tadalafil may last as long as 36 h. Tadalafil is also available in 5-mg tablets taken daily and also indicated in the treatment of prostatic hyperplasia.
  • The effect of avanafil begins after thirty minutes already, while the other drugs take about an hour to become effective.
  • PDE-5 inhibitors can be combined, as necessary.
    • For more severe ED, for instance, 5 mg tadalafil daily and 100 mg sildenafil before intercourse
  • Contraindications
    • Use of nitrates in any form
    • Unstable angina pectoris
    • Heart failure NYHA class IV
    • Strong susceptibility to arrhythmia
    • Severe obstructive cardiomyopathy
    • Severe aortic stenosis

Topical drugs

  • Intracavernous injections are the most effective pharmacological treatment for ED. They are also effective in patients who have diabetes or have undergone radical prostatectomy, in whom oral medication is poorly effective.
  • Injectable medication dilates the penile arteries quickly and effectively, increasing blood flow considerably.
  • The drug is injected with a thin 29G needle (Image 4) 7-10 mm into cavernous tissue. An autoinjector can be used.
  • Injection therapy requires guidance. A test injection should be given at the office to teach the patient the technique, alleviate fear of injection and get an idea of the dose required.
  • The drug used can be either alprostadil 10-20 µg or a combination of VIP peptide and phentolamine.
    • Both are effective in about 80-90% of patients.
    • The effect sets in, involuntarily, within minutes and lasts for about one hour. Alprostadil injections are associated with pain in the penis in about 11% of men; the risk of priapism is low (less than 3%).
      • Priapism can invariably be resolved by injecting 1 ml etilefrine into cavernous tissue. This will constrict the arteries in a few minutes and end the erection.
    • The combination of VIP peptide and phentolamine is not associated with pain in the penis or priapism. Patients find the erection more natural than with alprostadil. One patient in three experiences short-term facial flushing and erythema as adverse effects.
  • Alprostadil cream applied to the tip of the penis
    • The cream is sprayed at the urethral orifice.
    • It is rapidly absorbed; an erection occurs in 5-30 minutes and lasts for about an hour.
    • Erections will improve in 74-83% of patients.
    • Penile burning or pain occurs in about 40% of patients but only 3-4% stop the treatment due to adverse effects.
    • 2% of female partners have vaginal burning or itching.
    • Contraindications include trying to get pregnant and balanitis.
    • Topical alprostadil cream can be combined with oral medication.
  • Combinations other than the combination of two PDE-5 inhibitors or of alprostadil administered either intraurethrally or to the tip of the penis and a PDE-5 inhibitor should normally not be tried in primary health care.

Surgical treatments

  • Implantation of a penile prosthesis is the only significant surgical treatment.
    • Before implanting a prosthesis, every possible drug treatment must have been tried.
    • The cavernous tissues are replaced with penile implants. A fluid reservoir is implanted in the pelvic area; when a button is pushed, the fluid flows to the implants to produce an erection.
    • Patient and partner satisfaction are very high.

Other treatments

  • Testosterone
    • Testosterone treatment started with appropriate indication improves erection.
    • Overweight and metabolic syndrome are common causes of slightly reduced testosterone levels.
    • Weight loss may increase testosterone levels. However, the efficacy of weight loss is rather poor. Weight loss of about 10-15% will raise testosterone levels by 2-4 nmol/l, only. The effect of such a small increase in testosterone levels on erectile function is minor but it will improve the patient's quality of life.
    • If the testosterone level was originally > 12 nmol/l, testosterone treatment will in most cases not improve erectile or other sexual functions.
    • If testosterone levels are repeatedly 8-12 nmol/l and the patient also has other symptoms consistent with testosterone deficiency, a 6-month trial with testosterone can be considered.
    • If testosterone levels are repeatedly below 8 nmol/l, further investigations in specialized care are indicated.
  • Vacuum pump
    • Even though their efficacy is modest, pumps can be tried as the first-line treatment for elderly patients rarely having intercourse, for whom drugs or surgical treatment are not suitable.
    • For patients in whom drug therapy is ineffective and who do not wish to have intracavernous injections or surgical treatment
  • LISWT
    • Low-intensity shockwave treatment (LISWT) is a new treatment for ED with controversial efficacy.
  • Sexual counselling, sex or couples therapy
    • Knowledge about matters related to sexuality is poor in all age groups and often based on taboos, beliefs and vague stories. It is therefore important to provide matter-of-fact, scientifically based information.
    • If the patient experiences problems with his sexuality, sex therapy may help. If there are conflicts in the relationship, couples therapy has proven to be a good method of treatment.

Criteria for referral to specialized care, and investigations performed there

  • Severe ED warrants referral to an outpatient urology clinic or to a specialist with expertise in this field.
  • Criteria for referral
    • Primary or acquired ED if an organic cause is suspected (such as disorders of the circulatory system, diabetes) and treatments available to a general practitioner cannot resolve the problem
    • Surgical treatment considered, such as for Peyronie's disease or penile prosthesis
    • Treatment ineffective or causing complications
    • Patient with complex psychiatric or psychosexual disorder
    • Patient with complex endocrinological disorder
    • Medicolegal cause, such as sexual abuse, research purposes
  • Examinations in specialized care
    • Monitoring of nocturnal erections with a RigiScan® device
    • Circulation examinations
      • Intracavernous test injection
      • Doppler ultrasound examination
      • Dynamic infusion cavernosometry and cavernosography
      • Contrast study of pudendal arteries
    • Neurological investigations of bulbocavernosus reflex (BCR), nerve conduction velocity, for example
    • Endocrinological investigations
    • Psychodiagnostic investigations 1

    References

    • Allen MS, Walter EE. Health-Related Lifestyle Factors and Sexual Dysfunction: A Meta-Analysis of Population-Based Research. J Sex Med 2018;15(4):458-475. [PubMed]
    • Beecken WD, Kersting M, Kunert W, et al. Thinking About Pathomechanisms and Current Treatment of Erectile Dysfunction-"The Stanley Beamish Problem." Review, Recommendations, and Proposals. Sex Med Rev 2021;9(3):445-463. [PubMed]
    • Capogrosso P, Frey A, Jensen CFS, et al. Low-Intensity Shock Wave Therapy in Sexual Medicine-Clinical Recommendations from the European Society of Sexual Medicine (ESSM). J Sex Med 2019;16(10):1490-1505. [PubMed]
    • Hackett G, Kirby M, Wylie K, et al. British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men-2017. J Sex Med 2018;15(4):430-457. [PubMed]
    • Giagulli VA, Castellana M, Lisco G, et al. Critical evaluation of different available guidelines for late-onset hypogonadism. Andrology 2020;8(6):1628-1641. [PubMed]
    • Hatzichristou D, Kirana PS, Banner L, et al. Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires. J Sex Med 2016;13(8):1166-82. [PubMed]
    • Hatzimouratidis K, Salonia A, Adaikan G, et al. Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2016;13(4):465-88. [PubMed]
    • Kelly DM, Jones TH. Testosterone and obesity. Obes Rev 2015;16(7):581-606. [PubMed]
    • Maiorino MI, Bellastella G, Esposito K. Lifestyle modifications and erectile dysfunction: what can be expected? Asian J Androl 2015;17(1):5-10. [PubMed]
    • Moisidis K, Kalinderis N, Hatzimouratidis K. Current role of local treatments for erectile dysfunction in the real-life setting. Curr Opin Urol 2016;26(2):123-8. [PubMed]
    • Mulhall JP, Giraldi A, Hackett G, et al. The 2018 Revision to the Process of Care Model for Evaluation of Erectile Dysfunction. J Sex Med 2018;15(9):1280-1292. [PubMed]
    • Mykoniatis I, Pyrgidis N, Sokolakis I, et al. Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis. JAMA Netw Open 2021;4(2):e2036337. [PubMed]
    • Salonia A, Bettocchi C, Boeri L, et al. European Association of Urology Guidelines on Sexual and Reproductive Health-2021 Update: Male Sexual Dysfunction. Eur Urol 2021;80(3):333-357. [PubMed]
    • Salter CA, Mulhall JP. Guideline of guidelines: testosterone therapy for testosterone deficiency. BJU Int 2019;124(5):722-729. [PubMed]
    • Salonia A, Bettocchi C, Carvalho J, et al. EAU Guidelines on sexual and reproductive health. European Association of Urology 2022. http://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-Guidelines-on-Sexual-and-Reproductive-Health-2022_2022-03-29-084141_megw.pdf

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