What are the proven medical treatments for erectile dysfunction and how do they work?
Executive summary
Erectile dysfunction (ED) is treated with a stepped approach: lifestyle and addressing underlying disease, first-line oral phosphodiesterase type 5 inhibitors (PDE5-Is), then local mechanical or injectable therapies, and finally surgery for refractory cases — while several regenerative or device-based approaches remain experimental or conditional on trial data [1] [2] [3]. Understanding how each option works — vascular modulation, neural/hormonal correction, mechanical blood trapping, or prosthetic replacement — explains why treatments are chosen based on cause, comorbidity and patient preference [4] [5].
1. Oral first-line drugs: PDE5 inhibitors — what they do and why they work
PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are the established first-line pharmacologic therapy for most men with ED because they amplify the normal nitric-oxide–cGMP vasodilatory pathway in the penis: sexual stimulation releases nitric oxide, raising cGMP and causing cavernosal smooth-muscle relaxation and arterial inflow; PDE5-Is prevent cGMP breakdown and thereby improve erections [6] [2]. These drugs are generally safe and effective for vascular or mixed causes of ED, work within 30–60 minutes in many men (with agent-specific timing and duration differences), but are contraindicated with nitrates and require medical review for cardiovascular risk [7] [6] [2].
2. Mechanical and local options: vacuum devices, intraurethral and intracavernosal therapies
Vacuum erectile devices (VEDs) create negative pressure to draw blood into the corpora cavernosa and use a constriction ring to maintain rigidity, a non‑drug option often used when medications fail or are contraindicated [2] [1]. Local pharmacologic approaches include intraurethral alprostadil (MUSE) and intracavernosal injections of vasoactive agents (alprostadil, papaverine, phentolamine), which directly induce penile vasodilation and smooth‑muscle relaxation; these are effective even when systemic PDE5-Is are inadequate but carry risks such as penile pain and, rarely, priapism [8] [3].
3. Hormone replacement when low testosterone is driving symptoms
When biochemical hypogonadism is identified, androgen (testosterone) replacement can increase libido and sometimes improve erectile function, and combining testosterone therapy with PDE5-Is can help men who respond poorly to PDE5 inhibition alone; however, testosterone is only indicated when monitoring confirms deficiency and carries its own risks and contraindications [2] [5].
4. Surgical rescue: penile prostheses for refractory ED
For men who do not respond to or cannot use less invasive therapies, implanted penile prostheses — inflatable or malleable — provide a durable, reliable solution by mechanically producing rigidity; long‑term outcomes are favorable and prosthesis surgery is the standard surgical option after medical failure [8] [3]. Device selection and timing should weigh infection risk, patient dexterity, and expectations [8].
5. Emerging and experimental regenerative approaches: shockwaves, stem cells, PRP, gene therapy
Low‑intensity extracorporeal shockwave therapy (LiESWT) has shown promise in improving penile blood flow and endothelial function and may restore responsiveness in some men, but major societies currently consider many regenerative treatments experimental and recommend use within clinical trials [9] [3] [2]. Other approaches under investigation include stem cells, platelet‑rich plasma, gene therapy and novel central or peripheral neuromodulators; early data are intriguing but not yet definitive for routine practice [8] [10] [11].
6. Choosing therapy: cause, safety, comorbidity and realistic expectations
Treatment choice is driven by the underlying cause (vascular, neurologic, endocrine, psychogenic), patient cardiovascular status, medication interactions, and patient and partner preferences — clinicians often start with lifestyle changes and PDE5-Is, escalate to local devices or injections if needed, and reserve prostheses for refractory cases while counseling about risks and durability [1] [4] [5]. Where literature is limited or evolving (for instance, LiESWT, PRP, stem cells), authoritative bodies urge controlled trials before widespread adoption, so patients should expect informed, individualized decision‑making rather than one‑size‑fits‑all cures [9] [3].