Currently available treatments for erectile dysfunction are essentially unchanged for 20 years, and overall, men are not satisfied with their options. Furthermore, none of the currently available medical treatments offers a cure for ED… they simply treat the symptoms.
But there are several new treatments under development which could greatly improve ED treatment, and in some cases offer a permanent cure.
The treatments described below are experimental. That means several things:
- There is not enough clinical evidence to prove that the treatment actually works.
- Because the treatment is new and still being tested, the optimum protocol (treatment plan) is still being figured out.
- There may be side effects or health risks, some of which may not be known.
- It may be difficult to find a doctor who is qualified and willing to provide the treatment.
- Treatments may be expensive, and in most cases are not covered by insurance.
In a strongly-worded statement in March, 2018, the Sexual Medicine Society of North America (SMSNA) recommended that “the use of shock waves or stem cells or platelet rich plasma is experimental and should be conducted under research protocols in compliance with Institutional Review Board approval. Patients considering such therapies should be fully informed and consented regarding the potential benefits and risks. Finally, the SMSNA advocates that patients involved in these clinical trials should not incur more than basic research costs for their participation1.”
If these new treatments prove safe and effective, they may become mainstream in a few years. Until then, patients should only consider these treatments if they are offered by a licensed medical doctor, and preferable as part of a sponsored clinical study.
New and experimental treatments for erectile dysfunction include:
- Botulinum Neurotoxin (Botox®)
- Functional Electrical Stimulation (FES)
- Gene Therapy
- Melanocortin Receptor Agonists
- Platelet-Rich Plasma (PRP) Injection Therapy
- Priapus Shot® / P-Shot®
- Shockwave Therapy (LI-ESWT)
- Spider Venom
- Stem Cell Therapy
- Thermal Activated Penile Implant
- Topical Ointment (alprostadil)
- Topical Ointment (glycerol trinitrate)
A compilation of small studies – human and rat – has found that botulinum neurotoxin (Botox) injections may be an effective and long-lasting treatment for erectile dysfunction2. Preliminary research shows that Botox may be effective in treating severe cases of ED, and the effect may last for as long as six months.
A small clinical trial has shown that Functional Electrical Stimulation (FES) could be an effective treatment for erectile dysfunction3. In the trial, electrical stimulation was administered twice a week, over a period of four weeks. At the conclusion of the treatment, patients showed a statistically significant improvement in erectile function; a control group who received a placebo treatment did not show improvement.
Based on this trial, FES has potential as a treatment for ED. However, additional, larger-scale studies are needed. This treatment is currently not available commercially.
FES should not be confused with Transcutaneous Electrical Nerve Stimulation (TENS).
FES is the use of electrical stimulation to produce contractions in weak or paralyzed muscles. This contraction is combined with a functional activity where the targeted muscle is typically activated. In other words, just placing electrical stimulation on a muscle is not FES. The goal of FES is to pair electrical stimulation with activity and the person’s volition in order to promote nervous system repair and recovery.
TENS, on the other hand, is intended for temporary pain relief in sore and aching muscles or for symptomatic relief of chronic pain.
The FDA has approved TENS devices for sale in the United States. However, there is no evidence that these devices are effective in treating erectile dysfunction.
The potential for gene therapy is exciting, because it could be used to address several factors that contribute to ED, including nitric oxide levels, and regenerating smooth muscles, blood vessels and nerves. (See our article “How Do Erections Work?“)
Clinical studies are still in early phases (demonstrating the safety of the treatment, before larger trials evaluate its effectiveness). An early safety study showed significant improvement for several patients4 .
Drugs such as Bremelanotide (PT-141), which act on receptors in the brain, can increase feelings of sexual arousal in both men and women. Limited studies have shown positive results for men suffering from diabetic ED and psychological ED5. The drugs are not an effective treatment for ED due to vascular problems.
Patients experienced significant side-effects, including nausea and hypertension (increased blood pressure).
The drug was approved by the FDA on June 21, 2019, for treating female sexual dysfunction, but is not currently approved as an ED treatment.
PRP therapy uses the patient’s own blood to treat ED. Blood is drawn from the patient and placed in a centrifuge to remove the plasma, and concentrate platelets and growth factors. The concentrated blood is then injected into the penis in order to promote the development and growth of blood vessels and nerves.
PRP injections have been used for many years to promote healing in wounds and injuries. Treatment usually consists of one or more injections. There have been hundreds of clinical studies for PRP injections; most show little if any effect.
The therapy is now being extensively promoted as a treatment for ED. There are even claims that PRP injections can increase penis size. Neither claim is supported by clinical studies6 so far.
A review of the current research7, conducted in 2019, concluded that “Despite a global presence of PRP clinics and ongoing active marketing and public interest in regenerative medicine, no scientific evidence has been published to establish an evidence-based risk-benefit profile for PRP use for ED in humans.”
Priapus Shot® and P-Shot® are registered service marks of Studio Medicine, and refer to their proprietary procedures. These procedures include PRP injections, combined with other forms of treatment such as vacuum pumps. It is claimed that these procedures can help correct ED, and also increase the size of the penis.
We’ve been unable to locate any independent clinical trials to support these claims. Dr. Sheldon Marks, writing on the WebMD website8, states “there is no evidence to show it is scientifically proven to work as claimed and it has not been thoroughly tested for safety. Additionally, at a cost of several thousand dollars per shot, it’s an expensive gamble. Unless new research comes to light, I won’t be recommending this treatment to my patients.”
Low-Intensity Extracorporeal Shockwave Therapy (LI-ESWT), commonly called shockwave therapy, is used to treat ED caused by vascular problems. Administering low-intensity sound waves has been found to encourage the development of new blood vessels, and improve the function of smooth muscle and endothelial cells.
A portable device is coated with a lubricating gel and applied directly to the penis. The procedure is painless. Sessions may last from 10 to 30 minutes. Treatment requires several sessions per week, over a period of 6-12 weeks. A follow-up treatment may be scheduled 6 months later.
There are several studies that show promising results9 10 11 12, especially for men with mild to moderate ED caused by vascular problems13. A review of previous work14, conducted in 2017, found contradictory results, with some studies showing promise, some providing inconclusive findings and some even discouraging. However, another review conducted in 201915 found overall positive results.
A recent study showed that about half the men who have a successful outcome from LI-ESWT lose the beneficial affects after two years16, and require another treatment.
Because this treatment is administered externally, it does not require approval by the US Food & Drug Administration (FDA). LI-ESWT therapy is marketed under various brand names, including GAINSWave®, REGENAWAVE®, and SONICWAVE™, each with their own treatment protocol.
One consequence of this is that the treatment methodology is not standardized, and may vary from one clinic to another… so research results may not apply to all practitioners.
Still, given recent publications, we consider this a promising treatment option.
UPDATE: In November, 2019, a southern California company announced a home LI-ESWT unit which the company claims provides the same treatment protocol as clinical devices. (See our article on The Rocket.)
The bite of the Brazilian Wandering Spider (Phoneutria nigriventer) has been found to cause erections. Scientists are now testing the PnTx2-6 protein, which has been isolated from the toxin, in order to produce an oral medication. Several positive studies have been conducted with rats17 18 19; human trials have not yet been conducted.
Current oral medications for erectile dysfunction inhibit the effect of the PDE5 enzyme, which allows blood to flow out of the penis. The spider venom works on a different principle; it increases the production of Nitric Oxide (NO), which causes blood to flow into the penis. (See our article “How Do Erections Work?“)
PnTx2-6 may be effective for men who don’t respond to current medications, or who experience severe side effects from PDE5 inhibitors.
Stem Cell therapy uses the patient’s own stem cells to treat ED. Typically, fat cells are taken from the patient’s stomach; stem cells are extracted and injected into the penis in order to promote the development and growth of blood vessels and nerves. The process is very similar to PRP injections, but the two treatments should not be confused.
Stem cell treatments have been tested extensively in rats, and more recently in small human trials20. The results have been promising. In a study involving men who had been through prostate removal, more than half recovered erectile function sufficient for penetrative sex21.
Potential hazard associated with stem cell therapy include:
- Administration site reactions,
- The ability of cells to move from placement sites and change into inappropriate cell types or multiply,
- Failure of cells to work as expected, and
- The growth of tumors.
Current penile implants are complicated to install, and prone to mechanical failure. Researchers are experimenting with a new metal alloy that “remembers” a shape, and returns to that shape when heated by electrical induction24.
In theory, a user could cause the penis to become erect by passing an electrical induction device over it, causing the metal implant to stiffen. The implant surgery would be much simpler, and the device would be more reliable, than current implants.
The device is currently undergoing mechanical testing; human trials will not begin for several years.
Topical ointments or gels are applied directly to the penis 30-60 minutes prior to intercourse. One gel, Topiglan (1% alprostadil, an ingredient commonly used in penile injections and suppositories), was effective in approximately 40% of the men tested25.
Topical agents could be used in conjunction with oral medications (PDE5 inhibitors) to enhance erections.
Clinical trials have found alprostadil to be a safe and effective alternative to oral medications for ED26. However, the manufacturer has found that the gel loses potency in storage; a further trial is planned with a redesigned applicator.
Another alprostadil ointment, Vitaros, has been available in the UK since 2014. The FDA has twice rejected it for sale in the US due to safety concerns.
Another type of topical ointment uses glycerol trinitrate, which, when absorbed through the skin of the penis, increases the supply of nitric oxide. Nitric oxide relaxes the smooth muscles in the penis, allowing blood vessels to expand and increasing blood flow. In a Phase II clinical trial, it improved the ability to achieve an erection for about 25% of the test subjects27. The test used the lowest effective dose of the drug; future tested will use higher concentrations to see if more men show improvement.
For More Information
- SMSNA. “Position Statement:ED Restorative (Regenerative) Therapies.” Sexual Medicine Society of North America. <http://www.smsna.org/V1/images/SMSNA_Position_Statement_RE_Restorative_Therapies.pdf>
- Ghanem, Hussein; Raheem, Amr Abdel; AbdelRahman, Islam Fathy Soliman; Johnson, Mark; Abdel-Raheem, Tarek. “Botulinum Neurotoxin and Its Potential Role in the Treatment of Erectile Dysfunction.” Sexual Medicine Review. Jan 2018. Vol 6, No 1, pp 135–142.
- Averbeck, M A; Bragante, K; Carboni, C; Fornari, A. “An initial study on the effect of functional electrical stimulation in erectile dysfunction: a randomized controlled trial.” International Journal of Impotence Research. May 2018; 30(1 Pt 2).
- Melman, Arnold; Bar-Chama, Natan; McCullough, Andrew; Davies, Kelvin; Christ, George. “hMaxi-K Gene Transfer in Males with Erectile Dysfunction: Results of the First Human Trial.” Human Gene Therapy. Dec 2006. Vol. 17, No. 12.
- Ryu, Ji-Kan; Suh, Jun-Kyu; Burnett, Arthur L. “Research in pharmacotherapy for erectile dysfunction.” Translational Andrology and Urology. Ap 2017; 6(2): 207–215.
- Wu, Chien‐Chih; Wu, Yi‐No; Ho, Hsiu‐O; Chen, Kuo‐Chiang; Sheu, Ming‐Thau; Chiang, Han‐Sun. “The Neuroprotective Effect of Platelet‐rich Plasma on Erectile Function in Bilateral Cavernous Nerve Injury Rat Model.” The Journal of Sexual Medicine. Nov 2012. Volume 9, Issue 11, Pages 2838–2848.
- Scott, Susan; Roberts, Matthew; Chung, Eric. “Platelet-Rich Plasma and Treatment of Erectile Dysfunction: Critical Review of Literature and Global Trends in Platelet-Rich Plasma Clinics.” Sexual Medicine Reviews. Apr 2019. Volume 7, Issue 2, Pages 306-312.
- Marks, Sheldon. “Can PRP Injections Really Give You a Bigger Penis?” WebMD Men’s Health. Jun, 2016.
- Kalyvianakis, D; Memmos, E; Mykoniatis, I; Kapoteli, P; Memmos, D; Hatzichristou, D. “Low-Intensity Shockwave Therapy for Erectile Dysfunction: A Randomized Clinical Trial Comparing 2 Treatment Protocols and the Impact of Repeating Treatment.” Journal of Sexual Medicine. Mar 2018. 15(3):334-345.
- Srini, Vasan Satya; Reddy, Rahul Kumar; Shultz, Tamar; Denes, Bela. “Low intensity extracorporeal shockwave therapy for erectile dysfunction: a study in an Indian population.” The Canadian Journal of Urology. Feb 2015. 22(1).
- Fojecki, GL; Tiessen, S; Osther P.J. “Effect of Linear Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction-12-Month Follow-Up of a Randomized, Double-Blinded, Sham-Controlled Study.” Sexual Medicine. Mar 2018. 6(1):1-7.
- Lu, Z; Lin, G; Reed-Maldonado, A; Wang, C; Lee, Y.C.; Lue, T.F. “Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis.” European Urology. Feb 2017. 71(2):223-233.
- Xin, Zhongcheng; Guan, Ruili; Cui, Wanshou; Zhang, Xiaodong; Tian, Long; Xie, Yi; Lei, Hongen; Liu, Jihong; Wang, Tao. “PD69-04 Safety and Efficacy of Low Intensity Extracorporeal Shockwave in the Treatment of Vasculogenic Erectile Dysfunction: a Multi-Center, Double-Blind, Randomized Sham-Controlled Clinical Trial.” The Journal of Urology. Apr 2017.
- Fode, Mikkel; Lowenstein, Lior; Reisman, Yacov. “Low-Intensity Extracorporeal Shockwave Therapy in Sexual Medicine: A Questionnaire-Based Assessment of Knowledge, Clinical Practice Patterns, and Attitudes in Sexual Medicine Practitioners.” The Journal of Sexual Medicine. Jun 2017. 5(2): e94–e98.
- Sokolakis, Ioannis; Hatzichristodoulou, Georgios. “Clinical studies on low intensity extracorporeal shockwave therapy for erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.” International Journal of Impotence Research. Jan 2019.
- Kitrey, Noam D. ; Vardi. Yoram; Appel, Boaz; Shechter. Arik; Massarwi, Omar; Abu-Ghanem. Yasmin; Gruenwald, Ilan. “Low Intensity Shock Wave Treatment for Erectile Dysfunction—How Long Does the Effect Last?” Journal of Urology. Jul 2018.
- Dorey, G; Siegel, A; Nelson, P. “The Effect of a Pelvic Floor Muscle Training Program Using Active and Resisted Exercises on Male Sexual Function: A Randomised Controlled Trial.” 2015.
- Jung, A R; Choi, Y S; Piao, S; Park, Y H; Shrestha, K R; Jeon, S H; Hong, S H; Kim, S W; Hwang, T K; Kim K H; Lee J Y. “The effect of PnTx2-6 protein from Phoneutria nigriventer spider toxin on improvement of erectile dysfunction in a rat model of cavernous nerve injury.” Urology. Sep 2014, 84(3):730.e9-17. doi: 10.1016/j.urology.2014.05.030.
- Nunes, K P; Toque, H A; Borges, M H; Richardson, M; Webb, R C; de Lima, M E. “Erectile function is improved in aged rats by PnTx2-6, a toxin from Phoneutria nigriventer spider venom.” Journal of Sexual Medicine. Oct 2012, 9(10):2574-81. doi: 10.1111/j.1743-6109.2012.02878.x. Epub 2012 Aug 23.
- Lin, Ching-Shwun; Xin, Zhong-Cheng; Wang, Zhong; Deng, Chunhua; Huang, Yun-Ching; Lin, Guiting; Lue, Tom F. “Stem Cell Therapy for Erectile Dysfunction: A Critical Review.” Stem Cells and Development. Feb 2012. 10; 21(3): 343–351. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272247>
- Haahr, Martha Kirstine; Jensen, Charlotte Harken; Toyserkani, Navid Mohamadpour; Andersen, Ditte Caroline; Damkier, Per; Sørensen, Jens Ahm; Lund, Lars; Sheikhb, Søren Paludan. “Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial.” EBioMedicine. Mar 2016. 5: 204–210.
- Reed-Maldonado, Amanda B; Lue, Tom F. “The Current Status of Stem-Cell Therapy in Erectile Dysfunction: A Review.” World Journal of Men’s Health. Dec 2016. 34(3): 155-164.
- Soebadi, MA; Moris, L; Castiglione, F; Weyne, E; Albersen M. “Advances in stem cell research for the treatment of male sexual dysfunctions.” Current Opinion in Urology. Mar 2016. 26(2):129-39.
- Le, B; McVary, K; McKenna, K; Colombo, A. “A Novel Thermal-activated Shape Memory Penile Prosthesis: Comparative Mechanical Testing.” Urology. Jan 2017. 99:136-141.
- Goldstein, I; Payton, T.R.; Schechter, P.J. “A double-blind, placebo-controlled, efficacy and safety study of topical gel formulation of 1% alprostadil (Topiglan) for the in-office treatment of erectile dysfunction.” Urology. Feb 2001. 57(2):301-5.
- Anaissie, James; Hellstrom, Wayne JG . “Clinical use of alprostadil topical cream in patients with erectile dysfunction: a review.” Research and Reports in Urology. August 2016; 8: 123–131.
- Ralph, David J; Eardley, Ian; Taubel, Jorg; Terrill, Paul; Holland, Tim. “Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study.” The Journal of Sexual Medicine. Feb 2018, Volume 15, Issue 2, Pages 167–175.