What are the recommended management options for erectile dysfunction?

Management of Erectile Dysfunction

All men with erectile dysfunction should begin with cardiovascular risk assessment, testosterone measurement, and lifestyle modifications, followed by PDE5 inhibitors as first-line pharmacotherapy, with escalation to intracavernosal injections, vacuum devices, or penile prosthesis for refractory cases. 1, 2

Initial Assessment and Risk Stratification

Cardiovascular Evaluation

• ED often precedes coronary artery disease symptoms by 2-5 years, making cardiovascular assessment mandatory in all patients. 1
• Screen for diabetes, hypertension, hyperlipidemia, and metabolic syndrome, as these conditions both cause ED and indicate increased cardiovascular mortality risk. 3, 1
• Stratify patients into low, intermediate, or high cardiovascular risk categories before initiating treatment—high-risk patients should not receive ED treatment until cardiac stabilization. 2

Laboratory Testing

• Measure fasting glucose, lipid profile, and HbA1c to identify metabolic contributors. 1, 4
• Measure total testosterone levels in all men with ED, particularly those who fail to respond to PDE5 inhibitors. 3, 1
• Testosterone <230 ng/dL indicates hypogonadism requiring replacement therapy. 1
• Testosterone 230-350 ng/dL may benefit from replacement if symptomatic. 1
• Testosterone >350 ng/dL does not usually require replacement. 3, 1

Clinical History and Examination

• Obtain detailed sexual history distinguishing ED from other sexual dysfunctions, including onset, duration, and severity. 1, 4
• Assess for cardiovascular, neurological, and endocrine comorbidities. 1, 4
• Review all medications, particularly antidepressants, antihypertensives, and substances including tobacco and alcohol. 1
• Perform focused physical examination including blood pressure, genital examination, secondary sexual characteristics, and lower extremity pulses. 1, 4

First-Line Management: Lifestyle Modifications

Lifestyle changes reduce cardiovascular risk by up to 36% mortality reduction and directly improve erectile function. 3

• Smoking cessation reduces total mortality by 36% in men with coronary disease and improves endothelial function. 3, 1
• Regular dynamic exercise improves lipid profiles, blood pressure, glucose-insulin homeostasis, and endothelial function, reducing incident coronary disease by 30-50%. 3
• Weight loss and obesity management are essential, as obesity is a major modifiable risk factor. 1
• Mediterranean diet emphasizing fruits, vegetables, whole grains, legumes, nuts, fish, and limiting red meat. 3, 1
• Moderate alcohol consumption: <14 units/week for women, <21 units/week for men. 3, 1
• Optimize control of diabetes, hypertension, and cardiovascular disease. 1, 2

Second-Line Management: Oral PDE5 Inhibitors

PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are first-line pharmacotherapy, effective in 60-65% of patients including those with diabetes, hypertension, and spinal cord injury. 1, 4, 2

Dosing Strategies

Tadalafil:

• As-needed dosing: Start 10 mg prior to sexual activity, adjust to 5-20 mg based on response; maximum once daily. 5
• Daily dosing: Start 2.5 mg daily, may increase to 5 mg daily. 5
• Effective up to 36 hours after dosing. 5

Vardenafil:

• Start 10 mg approximately 60 minutes before sexual activity. 6
• Adjust to 5-20 mg based on response. 6

Critical Prescribing Considerations

• Absolute contraindication: concurrent nitrate use (regular or intermittent) due to risk of life-threatening hypotension. 6
• Caution with alpha-blockers: start PDE5 inhibitors at lowest dose due to additive hypotensive effects. 5, 6
• PDE5 inhibitors require adequate testosterone levels for full efficacy—check testosterone in non-responders. 3, 1
• Avoid in patients with congenital QT prolongation or those taking Class IA/III antiarrhythmics. 6

Dose Adjustments for Renal Impairment

• CrCl 30-50 mL/min: Tadalafil as-needed maximum 10 mg every 48 hours; daily dosing start 2.5 mg. 5
• CrCl <30 mL/min or hemodialysis: Tadalafil as-needed maximum 5 mg every 72 hours; daily dosing not recommended. 5

Dose Adjustments for Hepatic Impairment

• Moderate impairment (Child-Pugh B): Vardenafil start 5 mg, maximum 10 mg; Tadalafil maximum 10 mg once daily. 5, 6
• Severe impairment (Child-Pugh C): Not evaluated, use with extreme caution. 5, 6

Optimization

• Titrate doses to achieve optimal efficacy rather than accepting suboptimal response. 2
• Provide proper instructions on timing, sexual stimulation requirements, and expectations. 2, 6

Adjunctive Testosterone Replacement Therapy

• For confirmed hypogonadism (testosterone <230 ng/dL) with symptoms, testosterone replacement improves sexual function and enhances PDE5 inhibitor response. 1
• Testosterone alone improves libido but requires minimal threshold levels for complete PDE5 inhibitor efficacy. 3, 1
• Contraindicated in men seeking fertility. 1
• Requires interval monitoring of hemoglobin, liver enzymes, and prostate-specific antigen due to increased prostate cancer risk. 7

Third-Line Management: Invasive Therapies

Intracavernosal Injection Therapy

• Alprostadil, papaverine, or phentolamine injected directly into the corpus cavernosum is effective for PDE5 inhibitor failures. 1, 2, 8
• Produces erection in 5-20 minutes lasting up to one hour. 9
• Maximum frequency: 3 times per week with at least 24 hours between injections. 9
• Critical warning: Erections lasting >6 hours require immediate medical attention to prevent permanent penile damage. 9
• Common side effects include mild-to-moderate injection pain and bleeding at injection site. 9
• Contraindicated in men with sickle cell disease, leukemia, multiple myeloma, severe penile curvature, or penile implants. 9

Intraurethral Alprostadil

• Alternative local therapy option for patients unable to use oral medications or injections. 1, 2

Vacuum Constriction Devices

• Non-invasive mechanical option for patients who cannot use or do not respond to pharmacological treatments. 1, 2

Fourth-Line Management: Surgical Options

• Penile prosthesis implantation is reserved for patients with refractory ED who fail all less invasive treatments. 1, 2
• Multicomponent inflatable penile implants are associated with high patient satisfaction rates. 8

Psychosexual Therapy

• Useful adjunctive treatment in combination with medical and surgical treatments, particularly for psychogenic ED. 1, 2
• Cognitive-behavioral therapy and relationship counseling improve communication about sexual concerns and reduce performance anxiety. 4, 2
• Addresses psychological factors including depression, anxiety, stress, and relationship problems. 1

Critical Pitfalls to Avoid

• Failure to recognize ED as an early marker of cardiovascular disease—always evaluate cardiovascular risk factors. 2, 7
• Not checking testosterone levels, especially in PDE5 inhibitor non-responders. 3, 1
• Not titrating PDE5 inhibitor doses to achieve optimal efficacy. 2
• Prescribing PDE5 inhibitors without screening for nitrate use or cardiovascular risk stratification. 2, 6
• Not considering psychosexual factors that may contribute to or exacerbate ED. 2
• Failing to involve partners in treatment decisions when possible. 1