Which evidence‑based treatments should be considered first for men presenting with erectile dysfunction?
Executive summary
First-line, evidence-based therapy for most men with erectile dysfunction (ED) is an oral phosphodiesterase type 5 inhibitor (PDE5i), offered unless there are contraindications such as concurrent nitrate therapy; clinicians should pair medication decisions with a basic medical, psychosocial, and cardiovascular assessment because ED often signals systemic disease [1] [2] [3]. For men who cannot use or do not respond to PDE5is, guideline-backed second-line options include intracavernosal injections, vacuum erection devices, intraurethral alprostadil, and ultimately penile prosthesis when conservative measures fail; emerging regenerative therapies like low‑intensity extracorporeal shockwave therapy (LI‑ESWT) and platelet-rich plasma remain investigational and require cautious interpretation [4] [5] [6] [7].
1. PDE5 inhibitors: the default first step with caveats
Oral PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are the first-line, evidence-based choice for most men presenting with ED because randomized trials and guideline panels demonstrate efficacy, safety, and favorable tolerability compared with placebo, with no high-quality data proving one agent is categorically superior to another—selection is therefore individualized by timing, duration of effect, cost, and patient preference [1] [4] [8]. Contraindications and interactions—most importantly coadministration with nitrates and certain cardiovascular contexts—must be screened before prescribing, and clinicians should counsel that sexual stimulation is required for these drugs to work [1] [3].
2. Concurrent evaluation: look for causes and cardiovascular risk
Guidelines and reviews emphasize that ED is frequently a multi‑factorial symptom tied to age, smoking, diabetes, hypertension, obesity, depression, and cardiovascular disease; initial management should therefore include history, medication review, and targeted testing (including consideration of testosterone only when clinical signs of hypogonadism are present), because treating underlying conditions can improve erectile function and reduce broader health risk [9] [10] [6].
3. When first-line fails: evidence-based second-line therapies
For men who do not respond to or cannot take PDE5is, intracavernosal injections of vasoactive agents (eg, alprostadil) are effective and remain a well-supported option, especially in older or post‑surgical populations, while vacuum erection devices and intraurethral alprostadil offer non‑systemic alternatives; if these measures are unsuitable or unsatisfactory, surgically implanted penile prostheses are an established final option with predictable outcomes [11] [5] [4] [12].
4. Psychosexual and partner‑focused care: part of first‑line thinking
AUA guidance and practice reviews underline that treatment planning should address psychosocial contributors and partner needs—psychotherapy, sex‑therapy, and incorporating a partner in counseling can improve adherence and outcomes and are reasonable adjuncts either alongside PDE5i therapy or as primary therapy when psychogenic factors dominate [2] [1] [12].
5. Emerging and experimental modalities: promise, not yet primacy
Regenerative and device‑based innovations—LI‑ESWT, stem cell and platelet‑rich plasma protocols, and some external or novel prostheses—show preliminary promise but lack robust, long‑term randomized data to displace standard care; clinicians and patients should treat marketing claims cautiously, differentiate modalities such as radial versus focused shockwave treatment, and reserve these for clinical trials or carefully informed off‑label use [5] [6] [7].
6. Practical algorithm for initial care
Begin with a focused history and exam, identify reversible contributors, offer lifestyle modification and cardiovascular risk management, present PDE5i therapy as the recommended initial pharmacologic option unless contraindicated, add partner‑oriented counseling when relevant, and escalate to injections, devices, or prosthesis for nonresponders—documenting informed choice and offering referral to urology or sexual medicine when complexity or treatment failure arises [2] [9] [4].