The Latest Erection Enhancement Treatments: What The Evidence Shows in 2026

[Nelson Vergel]

By Nelson Vergel | ExcelMale.com | Updated 2025


Men exploring options for erectile dysfunction (ED) or penile enhancement today have far more choices than a blue pill. A growing number of off-label treatments — from injections to acoustic wave devices — are being used in sexual medicine clinics, and the evidence behind each one varies considerably. Some have randomized controlled trials supporting their use. Others are in early-phase trials or still largely theoretical.
This guide breaks down every major off-label penile treatment currently being used in clinical practice, explains how each one works, and gives you a clear picture of what the research actually shows. Whether you are a PDE5 inhibitor non-responder, someone exploring enhancement options, or a clinician reviewing the landscape, this is the most comprehensive overview available.

What you will learn in this article: • How neuromodulator (Botox) injections improve erections and enhance size • What the P-Shot (PRP) does and what clinical trials show • How shockwave therapy, PT-141, hyaluronic acid filler, stem cells, and gene therapy fit in • A full comparison table of all treatments by mechanism, evidence level, and duration

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1. Neuromodulator + Plasma Gel: A Combined Enhancement Protocol​

What It Is​

This is a multicomponent procedure that pairs botulinum toxin A (a neuromodulator) with autologous plasma gel derived from the patient's own blood. It targets both erectile function and penile girth in a single session.

How the Plasma Gel Component Works​

Blood is drawn from the patient, plasma is isolated by centrifugation, then heated at 55-60°C for approximately 12 minutes to produce a gel. That gel is injected into the subcutaneous plane of the penile shaft above Buck's fascia, into the corpora cavernosa, and into the submucosal space of the glans. The gel adds immediate volumetric enhancement while growth factors within the plasma promote tissue remodeling over weeks.

How the Neuromodulator Component Works​

Botulinum toxin A (BoNT-A), diluted in saline, is injected at 2-4 points along the penile shaft. The mechanism is temporary relaxation of smooth muscle in penile blood vessel walls, improving blood flow and potentially increasing flaccid length. Injections at the penile base bilaterally also relax the fundiform and suspensory ligaments, contributing to a subtle lengthening effect.

Duration and Evidence​

Effects last 3-6 months, matching the duration of BoNT-A action. Clinical data is emerging, with several published protocols and patent-level documentation of the combined approach. Full randomized controlled trial data on the combined protocol specifically remains limited, though the individual components have separate evidence bases (see BoCox section below).

2. BoCox (Priapus Toxin): Botox for Erectile Dysfunction​

What It Is​

BoCox is an intracavernosal injection of botulinum toxin type A (Botox, Xeomin, or Dysport) specifically for erectile dysfunction. The term was coined by Dr. Charles Runels, M.D., who also created the P-Shot. It is sometimes called Priapus Toxin.

Mechanism of Action​

Botulinum toxin disrupts the neuromuscular junction, preventing smooth muscle contraction in the corpus cavernosum. When these muscles relax, penile arterioles dilate, increasing blood inflow. This is mechanistically similar to how PDE5 inhibitors work, but via a completely different pathway. BoNT-A may also migrate along nerve pathways, potentially increasing parasympathetic tone and improving the neural component of erection. The standard dose is 100 units injected into the corpus cavernosum — 50 units per side.

The Clinical Evidence​

BoCox has more randomized controlled trial data behind it than most other off-label penile treatments:
• Cairo University Phase 1 trial: A small RCT of 24 men demonstrated safety and efficacy of BoNT-A for ED.
• Cairo University Phase 2 trial (published in Andrology): A double-blind, randomized, placebo-controlled trial of 70 men with ED refractory to oral PDE5 inhibitors. Outcomes measured included the SHIM score, Erection Hardness Score (EHS), peak systolic velocity, and Sexual Encounter Profile questionnaires.
• International Andrology London results: Nearly 50% of men receiving BoNT-A — all severe, end-stage ED patients who had failed Viagra and Trimix — reported significant erectile satisfaction compared to placebo.
• 2025 systematic review and meta-analysis (University College London, published in Sexual Medicine): Evaluated 2 RCTs and 4 retrospective studies measuring IIEF-EF scores, EHS, and Doppler ultrasound parameters. Concluded BoNT-A intracavernosal injection may serve as a first- or second-line option when conventional pharmacotherapy fails.

Key clinical point: BoCox is particularly relevant for men who have stopped responding to Viagra or Cialis. It works on a separate pathway and does not require prior sexual stimulation to initiate blood flow changes.

Procedure and Recovery​

A numbing cream is applied first. Four injections are delivered to the penile shaft using a 26-gauge needle. The injection process takes under 3 minutes. Effects begin within 1-2 weeks and last 3-6 months. The procedure can be repeated after effects wane.

3. The P-Shot (Priapus Shot): PRP for Erectile Function and Sensitivity​

What It Is​

The P-Shot (Priapus Shot) is an intracavernosal injection of platelet-rich plasma (PRP) isolated from the patient's own blood. The name comes from Priapus, the Greek god of sexual regeneration, and was coined by Dr. Charles Runels after he first injected himself in 2010. Because PRP is autologous, the risk of allergic reaction or immune rejection is minimal.

Mechanism of Action​

PRP is a concentrated fraction of blood containing platelets loaded with growth factors: PDGF, VEGF, TGF-beta, EGF, and others. When injected into penile tissue, these growth factors activate resident stem cells and stimulate angiogenesis (new blood vessel formation), collagen remodeling, and tissue regeneration. The goal is to address the underlying vascular and tissue damage causing ED, not just manage symptoms acutely.

Procedure​

Blood is drawn (typically 30-60 mL), placed in a specialized centrifuge to separate the platelet-rich plasma from red and white blood cells, and a topical anesthetic plus penile nerve block is applied. PRP is then injected into the corpus cavernosum and the glans using a fine needle. The entire procedure takes 30-60 minutes. Use of a vacuum erection device (VED) twice daily post-procedure significantly improves outcomes and is considered essential by most practitioners.

What the Research Shows​

The evidence for the P-Shot is promising but inconsistent:
• A 2025 review in UroPrecision identified 5 RCTs, 2 meta-analyses, and a systematic review. Significant variability in PRP preparation, concentration, dosage, and follow-up protocols has made it difficult to draw universal conclusions.
• Multiple 2024 meta-analyses found statistically significant improvements in erectile function scores in men receiving PRP injections.
• Combination studies show synergistic benefits: combining PRP with shockwave therapy extends positive effects; combining PRP with daily tadalafil converts PDE5i non-responders into responders.
• Cleveland Clinic's assessment: clinical trials have not yet definitively confirmed improvement in erections; most supportive reports come from practitioners rather than large controlled trials.

Bottom line on the P-Shot: The mechanism is scientifically sound and the safety profile is excellent given its autologous nature. The evidence is real but still maturing. The P-Long Protocol — 6 monthly PRP sessions combined with VED use and supplementation — has a pilot study showing meaningful gains in both length, girth, and erectile function.

4. Low-Intensity Extracorporeal Shockwave Therapy (Li-ESWT)​

What It Is​

Li-ESWT is the most extensively studied non-injection off-label treatment for ED. A wand-like device applies focused low-energy acoustic pulses to the penile shaft, crura, and base over a series of sessions. No anesthesia is required. Sessions typically last 15-30 minutes.

Mechanism of Action​

Acoustic waves cause controlled microtrauma (shear stress) at the tissue level. This triggers a biological cascade: release of angiogenic growth factors, formation of new capillaries (neovascularization), and improved endothelial function. Applied to the corpora cavernosa, this process directly addresses the vascular deficiency underlying most cases of organic ED. It is important to distinguish true Li-ESWT from radial pressure wave therapy — the latter is widely advertised at spa-like clinics but uses a different physics and has substantially weaker evidence.

Clinical Evidence​

Li-ESWT has one of the most robust evidence bases of any off-label ED treatment:
• A 2025 meta-analysis of 12 RCTs including 882 men with vasculogenic ED found statistically significant improvements in IIEF-EF scores and Erection Hardness Scores compared to sham therapy.
• University of Virginia long-term RCT: Sustained improvement in SHIM and EHS scores for up to 2 years post-treatment; decline observed by year 3, suggesting re-treatment intervals may be needed.
• Cochrane review: Li-ESWT improves penile rigidity in the short term. Long-term improvement is real but may not be perceived as clinically important by all men. Side effects and early discontinuation are uncommon.
• Best responders: Men with mild to moderate vasculogenic ED. Li-ESWT can also convert PDE5i non-responders into responders, making it a useful bridge therapy.

5. Hyaluronic Acid (HA) Filler for Penile Girth Enhancement​

What It Is​

Hyaluronic acid filler injection for penile girth enhancement is one of the fastest-growing off-label procedures in urology. Between 2020 and 2025, the leading provider network PhalloFILL expanded from 1 clinic to 30 while revenue grew over 1,000%. Demand is now outpacing the ability to train urologists. HA filler is FDA-approved for cosmetic use in the face and joints; its use in the penis is off-label.

Procedure​

The technique involves hydro-dissection — injecting a saline solution to create a space between Buck's fascia and Dartos fascia along the penile shaft — followed by injection of cross-linked HA gel into that space, then manual modeling. Cross-linking delays resorption by the body. The procedure takes about one hour under topical anesthesia.

Results and Reversibility​

HA filler adds immediate circumference, turning growers into showers and increasing flaccid hang. Results typically last 12-18 months as the body gradually metabolizes the filler. The procedure is fully reversible by injecting hyaluronidase, which rapidly dissolves the HA. This reversibility is a major advantage over permanent surgical options.

Evidence and Safety Profile​

A retrospective study of nearly 500 men presented at the 2024 AUA Annual Meeting showed that all complications were minor (Clavien-Dindo Grade I-II). Prospective data found no inflammatory signs or serious adverse reactions. However:
• The Sexual Medicine Society of North America (SMSNA) issued a 2024 statement citing a lack of high-quality studies, making informed consent limited.
• Highly cross-linked HA increases the risk of local inflammation, edema, and granuloma formation.
• A 2022 multi-center randomized active-controlled trial confirmed efficacy and safety of HA filler for penile girth enhancement with no significant impact on ejaculation.

Important note: HA filler for penile enhancement is a purely cosmetic and psychological intervention. It does not improve erectile function. Men seeking it should have realistic expectations about what it does and does not address.

6. PT-141 / Bremelanotide: The Brain-Based ED Treatment​

What It Is​

PT-141 (bremelanotide) is a synthetic peptide melanocortin receptor agonist that works through the brain rather than through penile blood vessels. It is FDA-approved as Vyleesi for hypoactive sexual desire disorder (HSDD) in premenopausal women. In men, all uses are off-label and investigational. PT-141 is available at compounding pharmacies as a subcutaneous injection or nasal spray.

Mechanism: Why It Is Different From Everything Else​

Every other treatment on this list works peripherally — relaxing smooth muscle, increasing blood flow, or adding volume to the penis. PT-141 works centrally. It activates MC4 receptors in the hypothalamus, triggering a dopamine cascade in the medial preoptic area that governs sexual desire and arousal. This neural signal travels down the spinal cord to the pelvic organs, initiating parasympathetic activity and penile erection. Because PT-141 does not rely on nitric oxide pathways, it can work even in men where PDE5 inhibitors have failed.

Clinical Evidence in Men​

In a major Phase 2 trial, 34% of men using bremelanotide reported meaningful improvement including the ability to achieve and maintain an erection for intercourse, compared to 9% on placebo. A Phase IIB trial in diabetic men with ED reported significant increases in IIEF scores. PT-141 may be especially useful when low libido accompanies erectile difficulty — it addresses both the mental and physical components simultaneously.

Dosing and Administration​

The standard dose is 1.75 mg subcutaneous injection into the abdomen or thigh, taken at least 45 minutes before sexual activity. Maximum one dose per 24 hours, no more than 8 doses per month. Effects begin within 30-90 minutes. Common side effects include flushing and nausea.
Critical safety note: Do not combine PT-141 injection with PDE5 inhibitors (Viagra, Cialis, Levitra). Concurrent use carries a risk of hypertension and priapism. If combining is desired, consult a physician and consider intranasal delivery at lower doses.

7. Stem Cell Therapy​

What It Is​

Stem cell therapy for ED uses mesenchymal stem cells (MSCs) derived from the patient's bone marrow, adipose tissue, or peripheral blood. These cells are injected into the corpus cavernosum with the goal of repairing damaged penile tissue, regenerating blood vessels, and restoring nerve function — addressing root causes rather than managing symptoms.

Mechanism​

MSCs can differentiate into multiple cell types, including smooth muscle cells, endothelial cells, and nerve-supporting cells. When injected into penile tissue, they release paracrine signals that reduce inflammation, stimulate angiogenesis, and promote neural repair. Studies combining stem cells with Li-ESWT have shown synergistic effects, with shockwave therapy potentially enhancing MSC engraftment and survival at the injection site.

Where the Evidence Stands​

Currently, stem cell therapy for ED is available primarily at specialized regenerative medicine centers or within formal clinical trial protocols. Studies are small and lack standardized preparation protocols. It is not yet a mainstream clinical offering, but the mechanistic rationale is strong and early human data is promising. Men interested in this approach should seek IRB-approved trial enrollment wherever possible.

8. Gene Therapy (Emerging Research)​

What It Is​

Gene therapy for ED involves delivering nitric oxide synthase (NOS) genes directly into penile tissue using viral or non-viral vectors. The goal is to restore the tissue's own ability to produce nitric oxide — the molecule at the center of erection physiology — rather than providing it externally through medication.

Current Status​

This approach is still in preclinical and early-phase human research. Animal model results are promising: experimental models show meaningful improvements in erectile function following NOS gene delivery. The therapy could theoretically produce lasting or permanent restoration of erectile function, as opposed to the temporary effects of all currently available treatments. Human availability is likely years away, pending regulatory approval and safety data.

Comparing All Treatments: Full Summary Table​

Use this table as a quick reference when evaluating options with your healthcare provider. All treatments listed are off-label or experimental.

Treatment	Mechanism	FDA Status	Best Evidence	Duration
Neuromodulator + Plasma Gel	Smooth muscle relaxation + autologous volumetric fill	Off-label	Early clinical / patent literature	3–6 months
BoCox (Priapus Toxin)	BoNT-A relaxes cavernous smooth muscle → blood flow	Off-label	2 RCTs + 2025 meta-analysis (UCL)	3–6 months
P-Shot (Priapus Shot)	PRP growth factors → angiogenesis + tissue repair	Off-label / experimental	5 RCTs (variable protocols)	6–18 months (variable)
Li-ESWT (Shockwave)	Acoustic neovascularization of corpus cavernosum	Off-label device	Multiple RCTs + Cochrane review	Up to 2 years
Hyaluronic Acid Filler	Subcutaneous volumetric girth enhancement	Off-label cosmetic	AUA retrospective (n=500); SMSNA caution	12–18 months; reversible
PT-141 / Bremelanotide	CNS melanocortin MC4 → dopamine → arousal + erection	Off-label (approved for women only)	Phase 2/3 trials; 34% responder rate	On-demand (45–90 min)
Stem Cell Therapy	MSC-mediated tissue regeneration + neovascularization	Experimental	Early-phase / preclinical	Unknown
Gene Therapy (NOS)	Nitric oxide synthase gene delivery to penile tissue	Experimental / preclinical	Animal models only	Potentially lasting

Combination Protocols: Stacking Treatments for Better Results​

Several of these treatments have documented synergistic effects when combined:
• BoCox + P-Shot: Botox facilitates blood flow while PRP stimulates vessel and collagen growth. Combined, results last longer and girth and length improvements are greater. Some men also report improved premature ejaculation control.
• P-Shot + Li-ESWT: An Italian research group demonstrated that combining PRP with shockwave therapy extends the positive effects on erectile function beyond either treatment alone.
• P-Shot + Daily Tadalafil: PDE5i non-responders converted to responders in a study combining PRP with daily tadalafil 5mg and on-demand vardenafil, with significant improvements in SHIM, Erection Hardness Score, and penile duplex readings.
• Li-ESWT + Stem Cells: Shockwave therapy may enhance MSC engraftment and survival, making combination protocols a focus of ongoing research.
• PT-141 + Topical or Low-Dose PDE5i (with medical supervision): Works on separate pathways — central arousal vs. peripheral vasodilation — with preliminary evidence of enhanced response when combined carefully at appropriate doses under physician oversight.

Frequently Asked Questions​

Which off-label penile treatment has the strongest clinical evidence?​

BoCox (intracavernosal botulinum toxin) and Li-ESWT currently have the strongest evidence bases, including randomized controlled trials, meta-analyses, and systematic reviews. The 2025 UCL meta-analysis for BoCox and the Cochrane review plus multiple RCTs for Li-ESWT put both treatments ahead of the others in terms of controlled data.

Can these treatments work if Viagra and Cialis have stopped working for me?​

Yes — this is actually where several of these treatments are most relevant. BoCox, Li-ESWT, and PT-141 all operate through pathways independent of PDE5 inhibition. The Cairo University BoNT-A trial specifically enrolled men for whom Viagra and Trimix had failed, and nearly 50% responded. PT-141 works through the CNS and does not rely on nitric oxide at all.

Are any of these treatments permanent?​

None of the currently available off-label treatments provide permanent results. HA filler lasts 12-18 months, BoCox and neuromodulator treatments last 3-6 months, Li-ESWT effects are durable up to 2 years before declining, and PRP results vary from 6 to 18 months. Gene therapy — still experimental — is the only approach with potential for lasting correction.

Is hyaluronic acid filler safe for penile girth enhancement?​

Short-term safety data from nearly 500 men at the 2024 AUA meeting showed only minor complications. However, the SMSNA cautions that long-term safety data is limited and informed consent is therefore imperfect. The reversibility with hyaluronidase is an important safety feature. Highly cross-linked HA carries higher risk of granuloma formation.

Can I combine PT-141 with Viagra or Cialis?​

Combining PT-141 injections with PDE5 inhibitors is not recommended due to risk of hypertension and priapism. If you want to explore combination use, intranasal delivery at lower doses under physician supervision may reduce this risk, but always discuss with a prescribing doctor before combining.

Where can I discuss these treatments with others who have tried them?​

The ExcelMale forum has active threads on penile health, TRT, peptides, and off-label treatments. You can post questions, share experiences, and get responses from men with firsthand knowledge as well as from clinically informed community members.

The Bottom Line​

The landscape of off-label penile treatments has expanded significantly over the past decade. Men now have access to treatments that work through vascular, neural, central nervous system, regenerative, and volumetric mechanisms — covering almost every physiological pathway involved in sexual function.
BoCox has the most controlled trial data for men who have failed conventional ED drugs. Li-ESWT is the most evidence-backed non-injection option. The P-Shot has a sound mechanism and growing clinical literature but needs more standardized trial data. HA filler is booming in popularity and is reversible, but long-term safety data is still accumulating. PT-141 fills a unique niche for men where libido and central arousal are part of the problem.
None of these treatments should be pursued without a thorough evaluation of underlying causes — vascular, hormonal, neurological, and psychological — by a qualified physician. Optimizing testosterone, addressing metabolic health, and managing cardiovascular risk remain the foundation of any sexual health protocol.

Medical Disclaimer This article is for educational purposes only and does not constitute medical advice. The treatments described are off-label or experimental and have not been approved by the FDA for the indications discussed. Always consult a qualified urologist or sexual medicine specialist before starting, stopping, or modifying any treatment. Individual results vary.

About the Author

Nelson Vergel is a chemical engineer (McGill University), MBA, and pharmaceutical consultant with over 40 years in men's health advocacy. He has been on testosterone replacement therapy since 1991 and is the founder of ExcelMale.com, the largest independent men's hormone health community with over 24,000 members. He is the author of Testosterone: A Man's Guide, Beyond Testosterone, and Built to Survive, and serves as Senior Consultant to Empower Pharmacy. He has served on NIH committees and FDA advisory panels throughout his career.