Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychological, and hormonal disorders; use of a medication can also be a cause. Evaluation typically includes screening for underlying disorders and measuring testosterone levels. Treatment options include oral phosphodiesterase inhibitors, intraurethral suppositories, intracavernosal injections, vacuum erection devices, and surgical implants.
(See also Overview of Male Sexual Function and Dysfunction.)
Erectile dysfunction (ED) is the inability to achieve or maintain an erection sufficient for sexual activity. The prevalence of ED increases with age, affecting the majority of men aged > 50 years (1). ED significantly impairs patients’ mental health and relationships.
Довідковий матеріал
1. Mark KO, Arenella K, Girard A, et al: Erectile dysfunction prevalence in the United States: Report from the 2021 National Survey of Sexual Wellbeing. J Sex Medicine 21(4):296-303, 2024. https://doi.org/10.1093/jsxmed/qdae008
Etiology of Erectile Dysfunction
There are 2 types of erectile dysfunction (ED):
Primary ED: The man has never been able to attain or sustain an erection
Secondary ED: Acquired later in life by a man who previously was able to attain erections
Primary ED is rare and is almost always due to psychological factors or clinically obvious anatomic abnormalities.
Secondary ED is more common, and > 90% of cases have an organic etiology. Many men with secondary ED develop reactive psychological difficulties that compound the problem (1).
Psychological factors must be considered in every case of ED. Psychological causes of primary ED include guilt, fear of intimacy, depression, or anxiety. In secondary ED, causes may relate to performance anxiety, stress, or depression. Psychogenic ED may be situational, involving a particular place, time, or partner.
The major organic causes of ED are physiological (organic)
Vascular disorders
Neurologic disorders
The most common vascular cause is atherosclerosis of cavernous arteries of the penis, often caused by smoking, endothelial dysfunction, and diabetes. Atherosclerosis and aging decrease the capacity for dilation of arterial blood vessels and smooth muscle relaxation, limiting the amount of blood that can enter the penis (see Overview of Male Sexual Function and Dysfunction: Erection). Endothelial dysfunction is a disease of the endothelial lining of the small arterioles that reduces the ability to vasodilate when needed to increase blood flow. Endothelial dysfunction appears to be mediated by reduced levels of nitric oxide and can result from smoking, diabetes, and/or low testosterone levels. Veno-occlusive dysfunction permits venous leakage, which results in inability to maintain erection.
Priapism, usually associated with trazodone use, cocaine use disorder, sickle cell disease, and intracavernosal injections used for erectile dysfunction may cause penile fibrosis and lead to ED by causing fibrosis of the corpora cavernosa and thus impairment of the penile blood flow necessary for erection.
Neurologic causes include stroke, partial complex seizures, multiple sclerosis, peripheral and autonomic neuropathies, and spinal cord injuries. Diabetic neuropathy and surgical injury are particularly common causes.
Complications of pelvic surgery (eg, radical prostatectomy [even with nerve-sparing techniques], radical cystectomy, rectal cancer surgery) are other common causes. Occasionally, transurethral resection of the prostate is a cause. Other causes include hormonal disorders (primary or secondary hypogonadism), medications, pelvic radiation, and structural disorders of the penis (eg, Peyronie disease). Prolonged perineal pressure (as occurs during bicycle riding) or pelvic or perineal trauma can cause ED.
Any endocrinopathy or aging with testosterone deficiency (hypogonadism) may decrease libido and cause ED. However, erectile function only rarely improves with normalization of serum testosterone levels because most affected men also have neurovascular causes of ED.
Numerous medications are possible culprits (see table Commonly Used Drugs That Can Cause Erectile Dysfunction). Alcohol can cause temporary ED.
Довідковий матеріал щодо етіології
1. Allen MS, Wood AM, Sheffield D: The psychology of erectile dysfunction. Current Directions Psychol Sci 32(5), 2023. doi: 10.1177/09637214231192269
Diagnosis of Erectile Dysfunction
Clinical evaluation
Screening for depression
Testosterone level
Evaluation should include history of drug use (which includes prescription medications and herbal products), alcohol use, pelvic surgery and trauma, smoking, diabetes, hypertension, and atherosclerosis and symptoms of vascular, hormonal, neurologic, and psychological disorders. Satisfaction with sexual relationships should be explored, including evaluation of partner interaction and partner sexual dysfunction (eg, vulvovaginal atrophy, dyspareunia, depression).
It is vital to screen for depression, which may not always be apparent. The Beck Depression Scale or, in older men, the Yesavage Geriatric Depression Scale (see table Geriatric Depression Scale [Short Form]) is easy to administer and may be useful.
Examination is focused on the genitals and extragenital signs of hormonal, neurologic, and vascular disorders. Genitals are examined for anomalies, signs of hypogonadism (eg, testicular atrophy), and fibrous bands or plaques (Peyronie disease). Poor rectal tone, decreased perineal sensation, or abnormal bulbocavernosus reflexes may indicate neurologic dysfunction. Diminished peripheral pulses suggest vascular dysfunction.
A psychological cause should be suspected in young healthy men with abrupt onset of erectile dysfunction (ED), particularly if onset is associated with a specific emotional event or if the dysfunction occurs only in certain settings. A history of ED with spontaneous improvement also suggests a psychological origin (psychogenic ED). Men with psychogenic ED usually have normal nocturnal erections and erections upon awakening, whereas men with organic ED often do not.
Of note, vasculogenic ED can often be the first sign of cardiovascular disease. As such, men with new-onset vasculogenic ED should be referred to a cardiologist for evaluation of previously undiagnosed cardiovascular disease.
Часто використовувані препарати, які можуть викликати еректильну дисфункцію
Class | Drugs |
|---|---|
Antihypertensives | Beta-blockers, clonidine, loop diuretics (probably), spironolactone, thiazide diuretics |
Central nervous system drugs | Alcohol, amphetamines, anticholinergics, anxiolytics, cocaine, monoamine oxidase inhibitors, opioids, selective serotonin reuptake inhibitors, tricyclic antidepressants |
Hormonal agents | 5-Alpha-reductase inhibitors, antiandrogens, estrogens, luteinizing hormone‒releasing hormone agonists and antagonists |
Others | Cancer chemotherapeutic agents, cimetidine |
Дослідження
Laboratory assessment should include measurement of morning testosterone level; if the level is low or low-normal, prolactin and luteinizing hormone (LH) should be measured. Evaluation for occult diabetes, dyslipidemias, hyperprolactinemia, thyroid disease, and Cushing syndrome should be done based on clinical suspicion.
Currently, duplex ultrasonography after intracavernous injection of a vasodilatory medication such as a mixture of prostaglandin E1, papaverine, and phentolamine is most often used to evaluate penile vasculature. Normal values include a peak systolic flow velocity > 25 cm/sec, end diastolic velocity < 5 cm/sec, and a resistive index > 0.8. Resistive index is the difference between peak systolic velocity and end-diastolic velocity divided by peak systolic velocity.
Rarely, in selected patients for whom penile revascularization surgery is being considered after pelvic trauma, pelvic arteriography, dynamic infusion cavernosography, and cavernosometry may be done.
Several sleep-entrained erectile episodes occur in healthy men. These erectile events, measured by nocturnal penile tumescence monitors, may help differentiate between organic and psychogenic etiology of erectile dysfunction.
Treatment of Erectile Dysfunction
Treatment of underlying causes
Medications, usually oral phosphodiesterase inhibitors (see table Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction)
Vacuum erection device or self-administered intracavernosal injections (ICI) or intraurethral prostaglandin E1 (second-line treatment)
If other treatments fail, surgical implantation of penile prosthesis
Sex therapy as indicated
Underlying organic disorders (eg, diabetes, prolactin-secreting pituitary adenoma, hypogonadism, Peyronie disease) require appropriate treatment. medications that are temporally related to onset of erectile dysfunction (ED) should be stopped or replaced. Depression may require treatment. For all patients, reassurance and education (including of the patient’s partner whenever possible) are important. Clinicians should use this encounter to discuss behavior modification (eg, dietary changes and weight loss).
For further therapy, an oral phosphodiesterase (PDE) inhibitor is typically tried first because it is easy to use and has a good safety profile. If therapy with a PDE inhibitor is ineffective and/or poorly tolerated due to side effects, other treatments (including vacuum erection devices [VEDs], intraurethral prostaglandin, and intracavernosal injections) may be used.
For cases of mild erectile dysfunction, low-intensity shockwave therapy (Li-SWT) is an emerging technique. Theoretically, it works by limiting fibrosis and stimulating angiogenesis in the corporal bodies.
For men with psychogenic ED, sex therapy should be the mainstay of treatment.
Лікарські препарати при еректильній дисфункції
First-line treatment of ED is usually an oral phosphodiesterase (PDE) inhibitor. Other medications used include intraurethral prostaglandin E1 or intracavernosal injections of a combination of papaverine and phentolamine or a combination of prostaglandin E1, papaverine, and phentolamine. However, because almost all patients prefer oral therapy, oral medications are used unless they are contraindicated or not tolerated.
Oral PDE inhibitors selectively inhibit cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5 (PDE5), the predominant phosphodiesterase isomer in the penis. These medications include sildenafil, vardenafil, avanafil, and tadalafil (see table Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction). By preventing the hydrolysis of cGMP, the medications promote the cGMP-dependent smooth muscle relaxation that is essential for normal erection. Although vardenafil and tadalafil are more selective for the penile vasculature than sildenafil, clinical responses and adverse effects of these medications are similar. In comparative clinical trials, these medications show comparable efficacy (60 to 75%) (1).
Пероральні інгібітори фосфодіестерази типу 5 для еректильної дисфункції
Medication | Onset of Action | Comments |
|---|---|---|
Avanafil | 30 minutes | Can be taken 15 minutes before intercourse Fatty food reduces absorption |
Sildenafil | 60 minutes | Duration of action: ≈ 4 hours Fatty food reduces absorption |
Tadalafil | 60 minutes | Duration of action: 24‒36 hours Low-dose tadalafil can be taken as a daily medication to provide baseline improvement in erectile function Low-dose daily tadalafil is also used to treat BPH-related urinary symptoms Can be taken with fatty food |
Vardenafil | 60 minutes | Duration of action: ≈ 4 hours Fatty food reduces absorption |
All PDE5 inhibitors cause direct coronary vasodilation and potentiate the hypotensive effects of other nitrates, including those used to treat coronary artery disease. The concomitant use of nitrates and PDE5 inhibitors can be dangerous and is contraindicated. Patients who only occasionally use nitrates (eg, for rare bouts of angina) should discuss the risks, selection, and proper timing of possible PDE5 inhibitor use with a cardiologist.
Adverse effects of PDE5 inhibitors include flushing, visual abnormalities, hearing loss, dyspepsia and headache. Sildenafil and vardenafil may cause abnormal color perception (blue haze). Tadalafil use has been linked with myalgias. Rarely, nonarteritic ischemic optic neuropathy (NAION) has been associated with PDE5 inhibitor use, but a causal relationship has not been established. All PDE5 inhibitors should be administered cautiously and at lower initial dosages to patients receiving alpha-blockers (eg, prazosin, terazosin, doxazosin, tamsulosin) because of the risk of hypotension. Patients taking an alpha-blocker should wait at least 4 hours before using a PDE5 inhibitor. Rarely, PDE5 inhibitors cause priapism.
Alprostadil (prostaglandin E1), self-administered via intraurethral insertion or intracavernosal injection, can produce erections with a mean duration of 30 to 60 minutes. Intracavernous alprostadil may be compounded with papaverine and phentolamine for increased efficacy when necessary. Excessive dosing may cause priapism in ≤ 1% of patients and genital or pelvic pain in about 10%. Office teaching and monitoring by the physician helps achieve optimal and safe use, including minimizing the risk of priapism, which is a urologic emergency that requires prompt intervention to reduce the risk of irreversible corporal fibrosis and complete ED. Intraurethral therapy is less effective at producing satisfactory erection than intracavernosal injection. Combination therapy with a PDE5 inhibitor and intraurethral alprostadil may be useful for some patients who fail to respond to oral PDE5 inhibitors alone.
Механічні пристрої та процедури
Men who can develop but not sustain an erection (eg, due to veno-occlusive dysfunction) may use a constriction ring to help maintain erection; an elastic ring is placed around the base of the erect penis, preventing early loss of erection. Men who cannot achieve erection can first use a vacuum erection device that draws blood into the penis via suction, after which an elastic ring is placed at the base of the penis to maintain the erection. Bruising of the penis, coldness of the tip of the penis, and lack of spontaneity are some drawbacks to this modality. These devices can also be combined with PDE5 inhibitor therapy if needed.
Low-intensity extracorporeal shock wave therapy (Li-SWT), which theoretically limits fibrosis in the corporal bodies, is under study as a treatment for erectile dysfunction (2).
Хірургічне втручання при еректильній дисфункції
Many nonsurgical ED treatments are available; however, these can be ineffective or impractical for men with moderate to severe ED. For these men, penile prosthesis surgery can be an effective option, achieving the highest patient and partner satisfaction rate of all ED treatments (3). Prostheses include semi-rigid silicone rods or saline-filled multicomponent inflatable devices. Implantation of both models carry the same risks (eg, those associated with use of general anesthesia, the possibility of postsurgical infection, and erosion or malfunction of the prosthesis). In the hands of experienced surgeons, the long-term rate of infection in primary penile prosthesis cases is well below 5%, even with involvement of trainees in the surgeries (4).
The advantages of surgical prosthesis implantation are obvious: erections are produced immediately and spontaneously, erections last until the patient deflates his device, and sexual activity may occur as frequently as the couple wishes. However, the primary disadvantages of penile prosthesis surgery (the need for invasive surgery, its irreversible nature, the potential for mechanical failure necessitating replacement surgery, potential postoperative complications such as infection and erosion of the device) should be carefully considered before such surgery is undertaken.
Довідкові матеріали щодо лікування
1. Tsertsvadze A, Fink HA, Yazdi F, et al: Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: A systematic review and meta-analysis. Ann Intern Med 151(9):650-661, 2009. doi: 10.7326/0003-4819-151-9-200911030-00150
2. Chung E, Cartmill R: Evaluation of long-term clinical outcomes and patient satisfaction rate following low intensity shock wave therapy in men with erectile dysfunction: A minimum 5-year follow-up on a prospective open-label single-arm clinical study. Sex Med 9(4):100384, 2021. doi: 10.1016/j.esxm.2021.100384.
3. Bettocchi C, Palumbo F, Spilotros M, et al: Patient and partner satisfaction after AMS inflatable penile prosthesis implant. J Sex Med 7(1 Pt 1):304-309, 2010. doi: 10.1111/j.1743-6109.2009.01499.x
4. McAbee KE, Pearlman AM, Terlecki RP: Infection following penile prosthesis placement at an academic training center remains low despite involvement of surgeons-in-training. Investig Clin Urol 59(5):342-347, 2018. doi: 10.4111/icu.2018.59.5.342
Ключові моменти
Vascular, neurologic, psychological, and hormonal disorders and sometimes medication use can compromise achievement of satisfactory erections.
Evaluate all men with ED for hormonal, neurologic, and vascular disorders and depression.
Measure testosterone levels and consider other testing based on clinical findings.
Treat underlying disorders and use an oral PDE5 inhibitor if necessary.
If oral PDE5 inhibitors are not effective or tolerated, other treatment options for ED include vacuum erection devices, intraurethral suppositories, intracavernosal injections, and penile prosthesis surgery.
