Erectile Dysfunction (ED)

Definition

Epidemiology

• In the Massachusetts Male Aging Study (MMAS), 52% of men aged 40-70 reported some degree of ED; complete ED occurred in 10%, moderate in 25%, and minimal in 17%.
• Incidence of moderate or severe ED more than doubled between ages 40 and 70.
• ~10-15% of all adult American men are affected.
• Higher rates in: type 2 diabetes mellitus, post-radical prostatectomy, cardiovascular disease, obesity, benign prostatic hyperplasia (BPH), hypertension, and lower spinal cord injury.
• ED represents a "sentinel symptom" for occult cardiovascular and peripheral vascular disease - the degree of ED correlates with severity of cardiovascular disease. - Harrison's, p. 3199

Pathophysiology

1. Failure to initiate - psychogenic, endocrinologic, or neurogenic causes
2. Failure to fill - arteriogenic (inadequate arterial inflow)
3. Failure to store - veno-occlusive dysfunction (venous leak)

The NO/cGMP Pathway (molecular basis)

Biochemical pathway modified by PDE-5 inhibitors - Harrison's Principles of Internal Medicine 22E

Causes by Category

Drugs Commonly Associated with ED

Diagnosis

• History: Detailed medical and sexual history; use validated tools such as the Sexual Health Inventory for Men (SHIM); assess libido, substance use, partner relationship.
• Physical examination: Genitourinary, cardiovascular, endocrine, and neurologic systems; prostate examination.
• Laboratory tests:
  • Morning serum testosterone
  • Fasting glucose or HbA1c
  • Lipid panel
  • PSA (if indicated)
  • Prolactin and LH/FSH (only if hypogonadism suspected)
  • Urinalysis, renal function, CBC
• Specific vascular/neurophysiologic tests are rarely required. - Goldman-Cecil Medicine, p. 2543

Treatment

Treatment Algorithm

Treatment algorithm for erectile dysfunction - Goldman-Cecil Medicine, adapted from EAU Guidelines 2010

First-Line: PDE-5 Inhibitors

• Effective in approximately 60% of men.
• Lower response rates in diabetes, spinal cord injury, post-prostatectomy.
• CONTRAINDICATED with nitrates (risk of severe hypotension due to cGMP accumulation).
• Caution with alpha-blockers (orthostatic hypotension risk).

Second-Line: Intracavernosal / Intraurethral

• Intracavernosal injection: Prostaglandin E1 (alprostadil), alone or combined with papaverine and/or phentolamine. Injected with 27-30 gauge needle into the cavernosal space. Side effects: pain, cavernosal fibrosis.
• Intraurethral alprostadil (MUSE): 125-1000 µg suppository; effective in 30-66% of cases.
• Vacuum erection devices: Non-pharmacologic option suitable for men who cannot tolerate medications.

Hormonal Therapy

• If serum testosterone is <275 ng/dL with symptoms of deficiency: testosterone replacement (gel, injections) can improve sexual function.
• Adding testosterone to sildenafil in partial responders does not provide additional benefit.

Psychosexual Counseling

• Beneficial when psychogenic factors are prominent or when treatments fail; may be combined with medical therapy.

Third-Line: Penile Prostheses

• Surgical implantation of semi-rigid (malleable) or inflatable devices.
• Reserved for men who fail all other therapies or prefer a permanent solution.
• Inflatable devices have ~10-20% mechanical failure rate at 10 years.
• Long-term patient and partner satisfaction is excellent with proper selection.

Special Populations

• Post-radical prostatectomy: PDE-5 inhibitors (on-demand dosing) aid sexual recovery. Recovery is gradual - 38% potent at 3 months, 86% at 18 months in nerve-sparing cases. - Campbell-Walsh-Wein Urology, p. 1955
• Diabetes: Higher ED prevalence; slightly reduced response to PDE-5 inhibitors; GLP-1 agonists (e.g., dulaglutide) may reduce incidence.
• SSRI-induced ED: Switch to bupropion, add a PDE-5 inhibitor, or consider a drug holiday.
• Cardiovascular disease: ED itself is a risk marker; assess cardiac risk. PDE-5 inhibitors do not cause ischemia and did not increase cardiovascular events in randomized trials, but are contraindicated with nitrates.

Key Takeaways

1. ED is multifactorial - organic and psychogenic causes almost always coexist.
2. It is a cardiovascular risk marker - always assess for underlying cardiometabolic disease.
3. PDE-5 inhibitors are first-line; work best when the NO pathway is at least partially intact.
4. Lifestyle modification alone can significantly improve ED in obese men.
5. Management should involve the patient's partner and address psychosocial factors alongside medical treatment.