Penile Injection Therapy For Erectile Dysfunction (ED)

Erectile dysfunction is more common than we think, and even young men experience this problem sometimes. 

There are many causes of erectile dysfunction, and the worst type is biological in nature. 

These causes are occasionally irreversible and cause long-lasting and very severe sexual dysfunction in men. 

When ED symptoms are caused by atherosclerosis, neurological problems, or circulatory issues, sometimes medications are not enough to counter the problem.

As a last resort, sometimes men with ED can benefit from penile injection therapy. We cover what this is and essential safety matters, including the side effects and risks involved in the procedure.

What is penile injection therapy?

Penile injection therapy is a self-injection procedure administered to the penis to treat erectile dysfunction (ED). Doctors might recommend this treatment for patients when other treatments have failed.

The injected drug usually consists of two or three medications combined in an aqueous solution. Together they increase the blood flow to the penile tissue and cause spontaneous erections (1).

One of the most commonly used treatments is known as Trimix. It includes phentolamine, alprostadil, and papaverine. There is also Bimix, which only includes phentolamine and papaverine. Some penile injections only contain papaverine.

How penile injection therapy works for ED

Alprostadil is one of the most critical components of Trimix injections. It is a prostaglandin, a substance that changes the way blood vessels behave. It causes vasodilatation in the blood vessels and inhibits the aggregation of platelets. By doing so, alprostadil increases the blood flow in the injected tissue of the penis. 

Besides increasing the blood flow, alprostadil has a relaxant effect on the penis and the corpus cavernosum. It also causes relaxation to the smooth muscle in the corpus spongiosum and the cavernous arteries. 

Even if they are contracted by noradrenaline, they would still increase the blood flow and facilitate erections. Arteries are now dilated, and trabecular smooth muscle is relaxed, so there’s no vascular cause for erectile dysfunction.

In one dose in the cavernous bodies, alprostadil injections induce erections 5-20 minutes after application. The duration of the effect depends on the amount administered in the injections (2).

After relaxing the muscle and dilating the arteries, these injections expand the lacunar spaces inside the penis. They are filled with blood, which is entrapped in the penis to obtain a stronger erection.

When it would be performed

Intracavernosal injections of Trimix, Bimix, papaverine, or alprostadil are indicated to treat erectile dysfunction in males. It is only reserved for male adults with a more complex case of erectile dysfunction that does not respond to conventional treatment. 

The first injections should be performed in the doctor’s office to train the patient and instruct him how to do it. Self-injections are only made by patients when they have been taught about the technique (3).

Injections should be administered 5-20 minutes before sexual intercourse. It can be administered during the arousal and foreplay period of sexual activity so that the drugs have enough time to act.

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Who is a suitable candidate?

As noted above, doctors only recommend penile injection therapy after trying or considering other treatments. 

Suitable candidates include (4,5):

  • Patients with a neurogenic ED: For example, patients with a spinal cord injury. The doctor should calculate the dose to obtain an erection suitable for intercourse but doesn’t hold for more than one hour.

There are also contraindications. You are not a suitable candidate in these cases:

  • In case of hypersensitivity (allergies) to the components of the drug

  • People with multiple myeloma, leukemia, and sickle cell anemia

Side effects

The reason why penile injection therapy is considered the last choice because it has more side effects than oral medications. Most of them are reversible and mild, but we should also consider more severe side effects.

Patients often experience the following side effects in order of frequency (6):

  • Discomfort in the injection site: This is the most common side effect, and almost all patients experience this problem at least once. 

  • Skin bruising of the penis: Some patients experience bruising and sometimes pain that lasts for a few days in the injection site. It is found in 1 in 3 patients.

  • Penile pain at the moment of the erection: Painful erections are more common in patients with penile fibrosis and Peyronie’s disease. However, even 1 out of 3-4 healthy patients experience this problem.

  • Bending or scarring of the penis: This side effect is less common and only happens in 1 out of 50 patients. There’s scarring inside the penis, similar to what happens in Peyronie’s disease. The penis starts bending after repeated injections. It usually occurs when the injection is administered in the same site repeatedly.

  • Urethral bleeding: This side effect is not common and only happens when the procedure is not performed correctly. A misplaced injection causes damage to the urethra and urethral bleeding in 1 out of 250 patients.

  • Priapism: This is perhaps the most feared side effect and a cause of drop-out of the treatment. Priapism is a persistent erection that lasts for more than 4 hours and feels painful. It is a medical emergency and requires hospital attention to drain the entrapped blood. It happens in less than 2% of patients.


Your risk is different depending on any pre-existing conditions and other circumstances. Thus, you should be carefully assessed by your urologist and listen to their advice to reduce your risk.

The most important risk we want to prevent is a prolonged erection and priapism. Avoiding this risk is usually achieved by calculating the appropriate dose of drugs and sticking to the doctor’s recommendation. 

The goal is to achieve an erection suitable for intercourse that does not last for more than 1 hour. Contact your doctor immediately if you still have an erection for 4 hours.

Patients with cavernous fibrosis, phimosis, angulation of the penis, penile fibrosis, Peyronie’s disease, and penile plaques are at a higher risk of painful erections. 

This symptom is only resolved when the drug is metabolized and eliminated. Thus, assessment of penile fibrosis and other penile comorbidities should be done before administering the treatment.

There is also a risk of bleeding in patients receiving heparin, warfarin, or other anticoagulants. Intracavernosal alprostadil reduces platelet aggregation and may increase the effects of the baseline treatment.


In the case of priapism, the most feared complication is hypoxia and necrosis of the penile tissue. There’s entrapment of blood inside the penis, which does not cause a problem when erections last for one hour. 

Erections longer than 4 hours are at a higher risk of causing blood flow changes in the penile tissue. Cells no longer receive oxygen and start to die, causing irreversible damage to the penis.

This complication will not happen if the dose of penile injections is calculated carefully, the patient follows instructions, and informs the doctor about any erection longer than 4 hours.

Another unexpected complication of penile injection therapy for ED is an infection in the injection site. This is more common in diabetic patients and only happens in 1 out of 250 patients. 


Penile injection therapy for ED is used in sexual medicine to stimulate the erectile tissue and achieve a complete penile erection. This method is only considered when oral ED medication, vacuum device, and other means are not successful or cannot be used by the patient. It is a successful ED treatment that relaxes the smooth muscle in the penis and facilitates the blood flow after sexual stimulation. 

It shouldn’t be used in a penile prosthesis, Peyronie’s disease, or penile curvature, and care should be taken in patients receiving anticoagulant treatment.

Priapism is the most feared side effect. Thus, prolonged erections should be notified immediately to prevent complications.

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  1. Coombs, P. G., Heck, M., Guhring, P., Narus, J., & Mulhall, J. P. (2012). A review of outcomes of an intracavernosal injection therapy programme. BJU international, 110(11), 1787-1791.
  2. Mitidieri, E., Cirino, G., di Villa Bianca, R. D. E., & Sorrentino, R. (2020). Pharmacology and perspectives in erectile dysfunction in man. Pharmacology & therapeutics, 208, 107493.
  3. Narus, J. B. (2017). Intracavernosal injection training. In Atlas of Office Based Andrology Procedures (pp. 117-127). Springer, Cham.
  4. Belew, D., Klaassen, Z., & Lewis, R. W. (2015). Intracavernosal injection for the diagnosis, evaluation, and treatment of erectile dysfunction: a review. Sexual medicine reviews, 3(1), 11-23.
  5. Moore, C. R., & Wang, R. (2006). Pathophysiology and treatment of diabetic erectile dysfunction. Asian journal of andrology, 8(6), 675-684.
  6. Lakin, M. M., Montague, D. K., Medendorp, S. V., Tesar, L., & Schover, L. R. (1990). Intracavernous injection therapy: analysis of results and complications. The Journal of urology, 143(6), 1138-1141.

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