What is the latest treatment for erectile dysfunction?

[Nelson Vergel]

A Comprehensive Guide to Current and Emerging ED Therapies for Men
Curated By Nelson Vergel | ExcelMale.com | Updated January 2026​

Introduction: Why ED Treatment Is Evolving​

Are you struggling with erectile dysfunction despite trying oral medications? You’re not alone. An estimated 322 million men worldwide will be affected by erectile dysfunction (ED) by 2025, making it one of the most prevalent conditions in men’s health. While phosphodiesterase type 5 inhibitors (PDE5Is) like sildenafil (Viagra) and tadalafil (Cialis) remain the gold standard first-line treatment, approximately 30-40% of men do not respond adequately to these medications—or experience intolerable side effects.

The good news is that the landscape of ED treatment has expanded dramatically. From regenerative therapies like low-intensity shockwave therapy (LiSWT) and platelet-rich plasma (PRP) to advanced surgical options like modern inflatable penile prostheses, men now have more options than ever before. This comprehensive guide will walk you through the latest evidence-based treatments, helping you understand what works, what’s emerging, and how to optimize your approach based on your specific situation.

Whether you’re new to ED treatment, a non-responder to oral medications, or on testosterone replacement therapy (TRT) looking to maximize sexual function, this article provides the clinical depth and practical guidance you need to make informed decisions with your healthcare provider.

Understanding Erectile Dysfunction: Causes and Risk Factors​

Erectile dysfunction is defined as the consistent or recurrent inability to achieve and/or maintain a penile erection sufficient for satisfactory sexual performance. The Massachusetts Male Aging Study found an overall prevalence of 52% in men aged 40-70, with the incidence increasing significantly with age. However, ED is not simply an inevitable consequence of aging—it often signals underlying health conditions that warrant investigation.

Primary Causes of ED​

Vasculogenic ED is the most common form, accounting for the majority of cases. It results from impaired blood flow to the penis due to atherosclerosis, endothelial dysfunction, or venous leak. This is why ED is often considered a sentinel marker for cardiovascular disease—the Prostate Cancer Prevention Trial found that men with ED were 45% more likely to experience a cardiac event within 5 years.

Neurogenic ED occurs when nerve damage disrupts the signaling required for erection. Common causes include diabetes, spinal cord injury, multiple sclerosis, and nerve damage following radical prostatectomy. These patients often require different treatment approaches than those with purely vascular causes.

Hormonal factors play a significant role, particularly low testosterone. Late-onset hypogonadism (LOH) is characterized by diminished serum testosterone levels and can cause decreased libido, reduced erectile function, and other symptoms. Men on TRT should have their levels optimized as part of any comprehensive ED treatment plan.

Psychogenic ED involves psychological factors including performance anxiety, depression, relationship issues, and stress. Even when the primary cause is organic, psychological factors frequently contribute and can amplify the problem.

First-Line Treatment: PDE5 Inhibitors​

Phosphodiesterase type 5 inhibitors (PDE5Is) remain the cornerstone of ED treatment and are recommended as first-line therapy by both the American Urological Association (AUA) and the European Association of Urology (EAU). These medications work by blocking the PDE5 enzyme, which breaks down cyclic guanosine monophosphate (cGMP)—the molecule responsible for smooth muscle relaxation in the penis and increased blood flow during arousal.

Comparing Available PDE5 Inhibitors​

Four PDE5Is are currently available: sildenafil (Viagra), tadalafil (Cialis), vardenafil, and avanafil (Stendra). While all have similar efficacy rates of approximately 60-85%, they differ in their pharmacokinetic profiles, which can guide patient selection.

Medication	Onset	Duration	Food Effect	Best For
Sildenafil	30-60 min	4-6 hours	High-fat delays	Occasional use
Tadalafil	16-45 min	Up to 36 hours	None	Daily/regular use
Vardenafil	25-60 min	4-5 hours	High-fat delays	Rapid onset needed
Avanafil	15-30 min	6+ hours	Minimal	Fastest onset

Table 1: Comparison of PDE5 Inhibitors for Erectile Dysfunction

A 2025 meta-analysis comparing these medications found that sildenafil achieves effective erections in 77-84% of patients at doses of 50-100mg. Tadalafil has emerged as the preferred option for many men due to its 36-hour duration, earning it the nickname "the weekend pill." This longer duration allows for more spontaneity and is particularly useful for men who prefer not to time medication around sexual activity. For men with concurrent benign prostatic hyperplasia (BPH), daily low-dose tadalafil (5mg) is uniquely beneficial as it addresses both conditions.

Why PDE5 Inhibitors Stop Working​

If you’ve found that ED pills that once worked are now less effective, you’re experiencing a common phenomenon. Reasons include disease progression, particularly worsening vascular health or diabetes, psychological factors such as performance anxiety, incorrect usage (taking with high-fat meals or inadequate sexual stimulation), and inadequate dosing. Additionally, underlying conditions like undiagnosed low testosterone can reduce PDE5I effectiveness.

Important: PDE5Is require sexual arousal to work—they enhance the natural erectile response rather than creating one. All PDE5Is are absolutely contraindicated with nitrate medications (including nitroglycerin) due to the risk of severe hypotension.

Testosterone Replacement Therapy and Erectile Function​

The relationship between testosterone and erectile function is complex but clinically important. While testosterone is not directly required for the physical mechanism of erection, it plays crucial roles in libido, sexual motivation, and the signaling pathways that support erectile response.

A 2024 Cochrane systematic review of 43 studies with over 11,000 participants found that testosterone replacement therapy (TRT) likely results in modest improvements in erectile function in hypogonadal men, with a mean difference of 2.37 points on the International Index of Erectile Function (IIEF-EF). However, this did not meet the threshold for minimal clinically important difference (MCID ≥ 4 points), suggesting that TRT alone may not dramatically improve erections for most men.

The clinical takeaway: TRT is most beneficial for libido and sexual desire rather than erectile mechanics. For men with both low testosterone and ED, combination therapy with a PDE5I plus TRT often yields better results than either treatment alone. The TRAVERSE Sexual Function Study demonstrated sustained improvements in sexual activity and desire over 2 years with testosterone therapy in men with confirmed hypogonadism.

For ExcelMale readers on TRT: If you’re optimized on testosterone but still experiencing ED, don’t assume adding more testosterone is the answer. Instead, ensure your cardiovascular health is optimized and consider adding a PDE5I or exploring second-line treatments.

Second-Line Treatments: Beyond Oral Medications​

When PDE5 inhibitors fail or are contraindicated, several effective second-line options exist. Both the AUA and EAU guidelines recommend these treatments for non-responders to oral therapy.

Intracavernosal Injection Therapy (ICI)​

Intracavernosal injections involve self-injection of vasoactive medications directly into the corpus cavernosum of the penis. This bypasses the need for sexual arousal and provides reliable erections within 5-20 minutes. The AUA and EAU both recommend ICI as a second-line therapy after PDE5I failure.

Alprostadil (prostaglandin E1) is the only FDA-approved agent for intracavernosal injection and is available commercially as Caverject and Edex. Clinical trials demonstrate that alprostadil produces satisfactory erections in approximately 80% of men across all ED etiologies, including those with diabetes, vascular disease, and post-prostatectomy ED.

Trimix (alprostadil + papaverine + phentolamine) is a compounded combination that is often more effective than alprostadil alone, particularly for severe ED. Studies show 73% of men achieve full erections with Trimix compared to only 28% with Bimix (papaverine + phentolamine without alprostadil). Trimix also requires lower doses of alprostadil, reducing the common side effect of penile pain that affects 20-40% of men using alprostadil monotherapy.

The main drawbacks of ICI therapy include the need for injection (which some men find psychologically difficult), risk of priapism (prolonged erection requiring medical intervention), and potential for penile fibrosis with long-term use. Proper training and dose titration are essential for safe, effective use.

Vacuum Erection Devices (VEDs)​

Vacuum erection devices are non-pharmacological, mechanical options that create negative pressure around the penis, drawing blood into the corpora cavernosa. Once erect, a constriction ring is placed at the base to maintain the erection. VEDs have efficacy rates of 50-80% and are particularly useful for men who cannot use medications or prefer a non-drug approach. They’re also commonly used for penile rehabilitation after prostatectomy.

Limitations include the somewhat artificial quality of the erection (the penis may feel cool and less rigid at the base), the need for a constriction ring, and partner acceptance issues. However, for the right patient, VEDs provide a reliable, safe option with minimal side effects.

Emerging Regenerative Therapies: LiSWT, PRP, and Stem Cells​

The most exciting developments in ED treatment involve regenerative therapies that aim to restore natural erectile function rather than simply treating symptoms. These treatments target the underlying pathophysiology—damaged blood vessels and nerves—with the goal of potentially curing or significantly improving ED.

Low-Intensity Shockwave Therapy (LiSWT)​

Low-intensity shockwave therapy uses acoustic waves to stimulate angiogenesis (formation of new blood vessels) and improve endothelial function in the penis. The therapy is non-invasive, typically involves 6-12 sessions over several weeks, and has shown promise particularly for mild to moderate vasculogenic ED.

A 2025 meta-analysis of 12 randomized controlled trials including 882 men demonstrated statistically significant improvements in IIEF-EF scores and erection hardness scores (EHS) following LiSWT compared to sham therapy. The EAU now recommends LiSWT, either alone or in combination with PDE5Is, for patients with mild vasculogenic ED or for those who prefer alternatives to oral therapy.

However, the 2025 Cochrane review notes that the current evidence base has methodological limitations, and the AUA still classifies LiSWT as investigational. Long-term durability data from a 2024 randomized trial showed that improvements in erectile function appeared to decline after 2 years, suggesting that treatment benefits may not be permanent and repeat sessions may be needed.

Recommended protocol: Too expensive! For mild ED, LiSWT monotherapy may be sufficient. For moderate ED, LiSWT with PDE5I combination shows better results. For severe ED, combination therapy with LiSWT plus daily tadalafil has shown the most promise.

Platelet-Rich Plasma (PRP) Therapy​

Platelet-rich plasma (PRP) therapy involves injecting concentrated platelets derived from the patient’s own blood into the corpora cavernosa. The platelets release growth factors that may promote tissue regeneration and angiogenesis.

A 2024 meta-analysis of 4 randomized controlled trials with 413 patients found that PRP showed significantly better efficacy than placebo at 1, 3, and 6 months in terms of IIEF scores. A larger 2024 analysis of 12 controlled trials with 991 patients confirmed these findings, showing a standardized mean difference of 0.59 favoring PRP.

However, results are not uniformly positive. A well-designed 2023 prospective, double-blind, placebo-controlled trial of 61 men found no significant difference between PRP and placebo, raising questions about which patient populations benefit most. Studies combining PRP with LiSWT appear to show enhanced efficacy compared to either treatment alone.

Current status: PRP is not FDA-approved for ED and is not covered by insurance. There is no standardized preparation method or dosing protocol. Neither the AUA nor EAU currently recommends PRP due to insufficient evidence. However, for men seeking alternatives to surgery, PRP remains a reasonable investigational option to discuss with a qualified provider.

Stem Cell Therapy​

Stem cell therapy represents perhaps the most exciting frontier in ED treatment. Mesenchymal stem cells (MSCs) derived from adipose tissue or bone marrow have demonstrated the ability to regenerate damaged blood vessels and nerves in preclinical studies. The cells work through paracrine signaling, releasing factors like vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF).

A 2025 systematic review in Frontiers in Medicine summarized significant progress in both clinical and preclinical studies. Early clinical trials have shown promising results—one Korean study of diabetic men treated with umbilical cord blood stem cells found that 6 of 7 patients regained morning erections at 6 months, and all achieved vaginal penetration with concomitant PDE5I use.

Current status: Stem cell therapy for ED remains experimental and is not approved by any major regulatory agency. Most studies are in preclinical or early clinical phases. While the potential is enormous, patients should be cautious of clinics offering stem cell treatments outside of clinical trials.

Surgical Treatment: Penile Prosthesis Implantation​

For men who have failed or cannot use other treatments, penile prosthesis implantation (PPI) represents the definitive surgical solution for ED. Modern inflatable penile prostheses (IPPs) provide reliable, on-demand erections with the highest satisfaction rates of any ED treatment.

Types of Penile Prostheses​

Inflatable penile prostheses (IPPs) are the gold standard, consisting of inflatable cylinders placed in the corpora cavernosa, a pump in the scrotum, and a fluid reservoir. Three-piece IPPs (such as the AMS 700 and Coloplast Titan) provide the most natural-feeling erection and are preferred by most patients and surgeons.

Malleable (semi-rigid) prostheses are simpler devices that can be bent upward for intercourse and downward for concealment. While less natural, they have fewer mechanical parts and may be appropriate for men with limited manual dexterity.

Outcomes and Satisfaction​

IPP surgery has been called one of the most influential developments in sexual medicine. Patient satisfaction rates consistently range from 80-92% across multiple studies, with partner satisfaction similarly high. A 2024 International Journal of Impotence Research review confirms that modern prostheses demonstrate superior results regarding infection rates, mechanical reliability, and overall satisfaction.

A 2025 study comparing outcomes in patients under 40 found that PPI is equally safe and effective in younger men, with vascular causes identified in 64% of cases. This reinforces that ED requiring surgical intervention is not solely a condition of older men.

Outcome Measure	IPP Range	Notes
Patient Satisfaction	80-92%	Highest of any ED treatment
Partner Satisfaction	76-91%	Strongly correlates with patient satisfaction
Mechanical Reliability	93-98% at 5 years	Modern devices highly durable
Infection Rate	1-3%	Reduced by antibiotic coatings
Revision Rate	~12% at 5 years	Usually for mechanical issues

Table 2: Penile Prosthesis Implantation Outcomes

Key considerations: PPI is an irreversible procedure—once implanted, natural erections will no longer be possible. Thorough preoperative counseling is essential to set realistic expectations regarding penile length (some perceive shortening) and the mechanical nature of the erection. For properly selected and counseled patients, however, PPI transforms quality of life.

A Practical Treatment Algorithm for Men with ED​

Based on current guidelines and evidence, here is a step-by-step approach to ED management:

Step 1: Comprehensive Evaluation​

• Complete medical history including cardiovascular risk factors, diabetes, medications
• Hormone panel including total and free testosterone, SHBG
• Assess psychological factors and relationship dynamics
• Consider penile Doppler ultrasound if vascular etiology suspected

Step 2: Lifestyle Optimization​

• Weight loss if overweight (visceral obesity strongly linked to ED)
• Regular cardiovascular exercise
• Smoking cessation
• Limit alcohol consumption
• Optimize sleep and stress management

Step 3: First-Line Medical Therapy​

• PDE5 inhibitor trial (sildenafil, tadalafil, or alternatives based on preference)
• TRT if hypogonadal (testosterone <300 ng/dL with symptoms)
• Combination PDE5I + TRT if both are indicated

Step 4: Second-Line Options (if PDE5Is fail)​

• Intracavernosal injection therapy (alprostadil or Trimix)
• Vacuum erection device
• Consider LiSWT for mild-moderate vasculogenic ED

Step 5: Surgical Treatment​

• Penile prosthesis implantation for refractory ED

Future Directions: What’s on the Horizon​

The ED treatment landscape continues to evolve rapidly. Several promising areas are under active investigation:

Gene therapy aims to deliver genes encoding proteins essential for erection, such as vascular endothelial growth factor (VEGF) or endothelial nitric oxide synthase (eNOS). By promoting angiogenesis and neurogenesis, gene therapy could potentially provide long-term or permanent improvement in erectile function for men with vascular or neurogenic causes.

Low-intensity pulsed ultrasound (LIPUS) is emerging as another non-invasive physical therapy modality. Similar to LiSWT, LIPUS delivers energy to penile tissue to stimulate regeneration. Early studies suggest it may accelerate angiogenesis and improve corpus cavernosum structure.

Combination approaches represent the likely future of ED treatment. Combining LiSWT with PRP, stem cells with shockwave therapy, or multiple regenerative modalities may prove more effective than any single treatment. Personalized, precision medicine approaches—matching treatment to specific ED etiology and patient characteristics—are expected to become mainstream.

Related ExcelMale Forum Discussions​

Explore these community discussions for additional insights and real-world experiences from men managing erectile dysfunction:
• Why ED Pills Stop Working—And What to Do Next: ED Treatment Landscape – Comprehensive discussion on PDE5I non-response and alternative treatments
• Erectile Dysfunction 2025: Breakthroughs & Best Practices in Clinical Management – Latest clinical advances and emerging therapies
• Treatment Options for Erectile Dysfunction – Overview of available treatment modalities
• Treatments for Men Who Fail to Benefit from ED Medications – Options for PDE5I non-responders
• Erectile Dysfunction Pharmacotherapy – Medication options and considerations
• How to Prevent and Reverse Erectile Dysfunction – Prevention strategies and lifestyle interventions
• What to Do About Erectile Dysfunction – Practical guidance for men experiencing ED
• Proactive Erectile Dysfunction Treatments Explained by Experts – Expert insights on proactive ED management
• Erectile Dysfunction Cure: Top Urologist Shares the Truth – Urologist perspectives on ED treatment
• Restorative Therapies for ED – Discussion of regenerative treatment options
• Unconventional Erectile Dysfunction (ED) Treatments – Alternative and emerging treatment approaches

Key References​

1. Yao WJ, et al. Advances in erectile dysfunction treatment research: a narrative review. Transl Androl Urol. 2025;14(7):2106-2117. PubMed
2. Fu X, et al. Advances in stem cell therapy for erectile dysfunction: preclinical evidence and emerging therapeutic approaches. Front Med. 2025;12:1519095. Full Text
3. Ergun O, et al. Low-intensity shockwave therapy for erectile dysfunction. Cochrane Database Syst Rev. 2025;7(7):CD013166. PubMed
4. Lee H, et al. Testosterone replacement in men with sexual dysfunction. Cochrane Database Syst Rev. 2024. Cochrane Library
5. Xu Z, et al. An updated systematic review and meta-analysis of the effects of testosterone replacement therapy on erectile function and prostate. Front Endocrinol. 2024;15:1335146. PubMed
6. Mao Q, et al. The efficacy of platelet rich plasma in the treatment of erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials. Aging Male. 2024;27(1):2358944. PubMed
7. Pyrgidis N, et al. The recommended treatment protocol for low-intensity shockwave therapy based on the severity of erectile dysfunction. Int J Impot Res. 2025;37:566-568. Nature
8. Pencina KM, et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. J Clin Endocrinol Metab. 2024;109(2):569-580. Oxford Academic
9. Leslie SW, et al. Alprostadil. StatPearls. Updated February 2025. NCBI Bookshelf
10. Dhaliwal A, Gupta M. PDE5 Inhibitors. StatPearls. Updated April 2023. NCBI Bookshelf
11. Van Renterghem K. Advances in penile prosthetics: current trends and future directions in erectile dysfunction treatment. Int J Impot Res. 2025;37:1-3. Nature
12. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84(1):50-56. PubMed

Medical Disclaimer​

Important: This article is intended for informational and educational purposes only and should not be construed as medical advice. The information provided does not replace consultation with a qualified healthcare provider. Erectile dysfunction can be a sign of underlying health conditions, including cardiovascular disease, diabetes, and hormonal disorders, that require proper medical evaluation and management.

Always consult with a urologist, endocrinologist, or other qualified healthcare professional before starting any treatment for erectile dysfunction. Treatment decisions should be individualized based on your complete medical history, current medications, and specific health circumstances. Never discontinue or modify prescribed medications without medical supervision.

About ExcelMale​

ExcelMale.com is a leading online community and resource for men’s health, with a particular focus on testosterone replacement therapy, hormone optimization, and sexual health. Founded by Nelson Vergel, the forum has grown to over 24,000 members and features a 20+ year archive of discussions, research, and real-world experiences.

Nelson Vergel is the author of two essential guides for men navigating hormone therapy: "Testosterone: A Man’s Guide" and "Beyond Testosterone" —both available through the ExcelMale website and major book retailers. These books provide comprehensive, evidence-based information for men seeking to optimize their health through informed hormone management.
Visit us at www.ExcelMale.com to join our community and access additional resources on men’s health.

 

[Nelson Vergel]

Thread 'Review on pharmacological treatments for ED'

Jun 9, 2023

In the past three decades, several pharmacological options have improved the treatment of erectile dysfunction (ED). Each treatment has unique efficacy and safety profiles. Tailoring oral therapy with PDE5 inhibitors (PDE5is) based on patient profiles, such as age, relationship status, and intercourse frequency, is crucial. Oral PDE5is can be daily or on-demand, depending on patient needs. If oral treatments fail, or if there are contraindications, intracavernous injection (ICI) therapy with alprostadil can be considered. Combining multiple treatments in parallel has become a...

• madman
• erectile dysfunction; pde5i; injections
• Replies: 3
• Forum: When TRT Is Not Enough (ED, Libido, & More)

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