Erectile disfunction

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Erectile Dysfunction (ED)

Definition

Erectile dysfunction is the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. It is distinct from problems with libido, ejaculation, or orgasm, although those can coexist.

Goldman-Cecil Medicine, p. 2542

Epidemiology

Affects 10-15% of all adult American men; in men aged 40-70, approximately 52% report some degree of ED
Prevalence is significantly higher in men with type 2 diabetes mellitus and after radical prostatectomy
ED is associated with lower urinary tract symptoms/BPH and carries an increased risk of cardiovascular disease
Global estimates project ED will affect 322 million men worldwide
Goldman-Cecil Medicine, p. 2543

Pathophysiology

Erection is a neurovascular event mediated through nitric oxide (NO):

Sexual stimulation triggers non-adrenergic, non-cholinergic (NANC) nerve activity
Endothelial cells and nerve terminals release nitric oxide
NO activates guanylyl cyclase → increases cGMP → relaxes cavernous smooth muscle
Cavernous sinusoids fill with blood → venous plexus is compressed against the tunica albuginea → erection

In ED: Endothelial dysfunction → reduced NO production → decreased smooth muscle relaxation → failure of erection.

Etiological Categories

Category	Examples
Vasculogenic	Atherosclerosis, hypertension, hyperlipidemia, smoking (most common overall cause)
Neurogenic	Diabetes neuropathy, spinal cord injury, multiple sclerosis, post-prostatectomy
Endocrine	Hypogonadism (low testosterone), hyperprolactinemia, hypothyroidism
Psychogenic	Anxiety, depression, relationship problems, performance anxiety
Iatrogenic/Drug-induced	See drug table below
Systemic illness	Renal failure, hepatic disease, cardiovascular disease
Aging	Impaired penile vasodilatory capacity despite normal testosterone

ED and cardiovascular disease share common risk factors (smoking, obesity, metabolic syndrome, hyperlipidemia, type 2 DM) - men with ED should be assessed for cardiovascular disease.

Goldman-Cecil Medicine, p. 2543; Textbook of Family Medicine 9e, p. 1193

Drugs Commonly Causing ED

Drug Class	Examples
Antidepressants	SSRIs, TCAs, MAOIs
Antihypertensives	Beta-blockers, verapamil, clonidine
Cardiac drugs	Amiodarone, digoxin
Antiandrogens	Spironolactone, finasteride, GnRH agonists
Others	Alcohol, marijuana, opioids, antipsychotics

Medications account for up to 25% of cases.

Textbook of Family Medicine 9e, p. 1193; Goldman-Cecil Medicine Table 216-9

Diagnosis

History

Full medical and sexual history (onset, duration, quality of erections, morning erections, libido, partner factors)
Screen for psychosocial factors: depression, anxiety, relationship quality, substance use
Use validated tools like the Sexual Health Inventory for Men (SHIM) / International Index of Erectile Function (IIEF)
Review all medications

Physical Examination

Focus on:

Genitourinary - penile, testicular exam; signs of Peyronie's disease
Endocrine - signs of hypogonadism (gynecomastia, small testes, reduced body hair)
Cardiovascular - peripheral pulses, blood pressure
Neurologic - perineal sensation, bulbocavernosus reflex
Prostate - digital rectal exam (ED commonly co-occurs with BPH)

Laboratory Tests

Morning serum testosterone (mandatory)
Fasting glucose or HbA1c
Lipid profile
PSA (if prostate disease suspected)
Prolactin + LH + free testosterone only if hypogonadism suspected (hyperprolactinemia causes ED in <2% of cases)
Urinalysis, CBC, renal/hepatic function

Specific diagnostic tests (penile Doppler ultrasound, nocturnal penile tumescence testing) are rarely required in routine practice.

Goldman-Cecil Medicine, p. 2543; Textbook of Family Medicine 9e, p. 1193

Treatment

1. Address Underlying Causes First

Treat metabolic risk factors (diabetes, hypertension, dyslipidemia)
Weight loss in obese men can restore erectile function
Discontinue offending medications where clinically feasible
Psychosexual counseling for psychogenic ED

2. PDE-5 Inhibitors (First-Line Oral Therapy)

The advent of oral PDE-5 inhibitors made them the drugs of first choice. They work by blocking the breakdown of cGMP, potentiating the NO-mediated erection pathway. They require sexual stimulation to work.

Drug	Dose	Onset	Duration
Sildenafil (Viagra)	25-100 mg on demand	20-60 min before	~4-6 hrs
Vardenafil (Levitra)	10-20 mg on demand	30-60 min before	~4-6 hrs
Tadalafil (Cialis)	10-20 mg on demand OR 2.5-5 mg daily	30-60 min / any time daily	Up to 36 hrs
Avanafil (Stendra)	50-200 mg on demand	~15-30 min	~6 hrs

Efficacy: ~60% of men overall; lower rates in diabetics, post-prostatectomy, post-pelvic irradiation.

Key contraindication: Must NOT be combined with nitrates (severe hypotension risk).

Goldman-Cecil Medicine, p. 2543

3. Second-Line Therapies

Alprostadil (PGE1) - intracavernosal injection (Caverject) or intraurethral suppository (MUSE); highly effective
Vacuum erection device (VED) - non-pharmacologic mechanical option
Combination therapy - PDE-5i + intracavernosal injection or + vacuum device

4. Hormonal Therapy

If hypogonadism is confirmed (low testosterone), testosterone replacement therapy (TRT) may restore erectile function and improve PDE-5i response
Testosterone alone is insufficient in most cases; often combined with PDE-5i

5. Emerging / Investigational Therapies

Low-intensity shockwave therapy (Li-SWT) - mechanistically promotes neovascularization; 2025 EAU Guidelines give it a weak recommendation due to limited data
Platelet-rich plasma (PRP) - no recommendation from 2025 EAU guidelines (insufficient data)
Stem cell therapy - investigational

6. Surgical

Penile prosthesis implant (inflatable or malleable) - reserved for cases refractory to all other treatments; high patient satisfaction (~90%)

Special Considerations

Post-prostatectomy ED: Recovery is gradual; 38% potent at 3 months, 54% at 6 months, 73% at 12 months, 86% at 18 months. Key factors: younger age (<65), pre-op potency, bilateral nerve-sparing surgery. PDE-5i on-demand (rather than nightly) is the preferred rehabilitation strategy.

Campbell Walsh Wein Urology, p. block85

SSRI-induced ED: Options include adding a PDE-5i, switching to bupropion, or a drug holiday.

Cardiovascular safety of PDE-5i: No increase in cardiovascular events or death shown in randomized trials. The drug does not cause ischemia. However, sexual exertion itself carries cardiac risk - assess cardiovascular fitness before recommending sexual activity.

Recent Evidence (2024-2026)

A 2026 systematic review and meta-analysis (PMID: 40797370) found that combination therapy (PDE-5i + regenerative therapies such as Li-SWT or PRP) was superior to monotherapy alone for improving erectile function scores. A 2024 network meta-analysis (PMID: 39419772) on regenerative therapies found Li-SWT to have the best evidence among regenerative options, though data remain heterogeneous.

The 2025 EAU Guidelines (European Association of Urology) continue to emphasize individualized, shared decision-making, progressing from least to most invasive interventions, with PDE-5i remaining the cornerstone of first-line treatment.

Summary: ED is a common condition with multifactorial causes - vasculogenic causes predominate. It is an important marker of cardiovascular risk. Treatment starts with lifestyle modification and addressing underlying conditions, followed by oral PDE-5 inhibitors as first-line pharmacotherapy, with escalation to intracavernosal therapy or surgery for refractory cases.

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