Overview of erectile dysfunction (ED)

The definition of erectile dysfunction (ED) is the inability to achieve or sustain a penile erection in order to facilitate successful sexual intercourse. The condition is increasingly common in men over the age of 40 and while probably underreported, affects at least 52% of men between the ages of 40 and 70 to some extent.¹ The mechanisms underlying ED are complex and involve psychological, physical and lifestyle factors. While the incidence of ED increases with age, the possibility of developing ED is strongly associated with co-existing conditions including: coronary artery disease, obesity, depression, high cholesterol, diabetes, underactive thyroid, low testosterone levels, benign prostate enlargement, previous prostate surgery or radiotherapy (particularly radical prostatectomy for prostate cancer) and the side effects of prescription medications. Lifestyle factors such as smoking, lack of exercise, increased alcohol intake and the use of recreational drugs also increase the risk.² 

The inner layer of the penis is composed of three masses of sponge-like tissue : the two corpora cavernosa and the corpus spongiosum. During sexual stimulation nerve impulses from the parasympathetic nervous system travel from the spinal cord to the penis and stimulate the production of nitric oxide, which results in a chemical cascade that leads to dilation of the arteries into the penis, filling these sponge like masses of tissue with blood resulting in an erection. Nitric oxide promotes the production of a chemical called cyclic guanosine monophosphate (cGMP) which causes the walls of the arteries in the penis to relax to allow increased blood flow into the penis. cGMP is removed by an enzyme called phosphodiesterase-5, which then reverses the process.³ It is this enzyme - phosphodiesterase-5 that is inhibited by drugs used to treat ED, such as Viagra (sildenafil).³ Anything that damages the blood supply to the penis - such as atherosclerosis (hardening of the arteries), diabetes, smoking or high cholesterol, or the nerve supply - such as prostate surgery and diabetes may predispose to erectile dysfunction. Likewise, treatments for ED are designed to increase blood flow into the penis.

There are many different treatments available for ED. In milder cases, simple lifestyle changes such as losing weight, quitting smoking, increasing physical exercise, avoiding alcohol and where possible changing prescription drugs (such as antidepressants, certain blood pressure medications and others) may be sufficient.⁴ However, the phosphodiesterase-5 inhibitor class of drugs which includes sildenafil (Viagra), tadalafil (Cialis) and avanafil (Stendra), has revolutionised the treatment of ED for many men. Despite their effectiveness and generally well-tolerated side effect profile, these drugs are not suitable for all men with ED, either due to a lack of response to treatment, side effects or complications. Furthermore, these medications usually need to be taken “on-demand” (although daily dosing with tadalafil is an option, particularly for patients with benign prostate disease) affecting the spontaneity of intercourse.⁵ Less commonly used treatments for ED include prostaglandin injections into the penis, vacuum devices and in cases where all other measures have failed, prosthetic devices surgically implanted into the penis.4 Extracorporeal shock wave therapy (ESWT) represents a relatively new approach to the treatment of ED, either as a sole treatment, or in combination with phosphodiesterase-5 inhibitor drugs.

Introduction to extracorporeal shock wave therapy (ESWT)

Extracorporeal shock wave therapy involves transmitting pulses of acoustic energy through the tissues known as shock waves. Depending on the amount of energy transmitted, extracorporeal shock wave therapy is classified as high, medium or low intensity. High-intensity ESWT is used in treatment to break up kidney stones so that they can be passed in the urine (lithotripsy). Medium intensity ESWT is used in musculoskeletal conditions such as tendonitis and has an anti-inflammatory action. Low-intensity ESWT is known to promote the growth of new blood vessels and has been used following damage to the heart due to cardiovascular disease.⁶ In 2010 Vardi and colleagues first studied the effect of low intensity ESWT on symptoms of erectile dysfunction.⁷ The types of shockwaves are also classified by the method used to generate them, namely: Piezo-electrical, electro-magnetic or electro-hydraulic. The generator is attached to a probe which can be placed directly over the surface of the penis thus directly transmitting the shock waves to the tissues of the corpora cavernosa, the spongy tissue that fills with blood during a penile erection.⁶

Mechanism of action of ESWT in erectile dysfunction (ED)

The exact mechanism by which ESWT improves penile blood flow in erectile dysfunction is not fully understood, however, it is thought to promote the formation of new blood vessels in the tissues, known as neovascularisation. The effects of low-intensity ESWT on damaged cardiac muscle have been extensively studied in animals.⁸ Furthermore, clinical trials in humans with ischaemic heart disease have shown improvement in clinical outcomes following delivery of low-intensity ESWT. In ED, ESWT is thought to work by a number of mechanisms. By causing mechanical disruption in the tissues of the penis, a number of chemicals that promote the growth of new blood vessels, including vascular endothelial growth factor (VEGF), are produced.⁹ It is proposed that this leads to the formation of new microscopic blood vessels and promotes re-modelling of the tissue of the corpora cavernosa, leading to better erections.

Clinical evidence

Since the initial study of the effects of ESWT on ED in 2010⁷, there has been a steadily growing body of research conducted in this area. One of the challenges with interpreting this clinical research is that there have been conflicting reports, making it difficult to reach a general consensus about the effectiveness of this treatment. One solution to this is to analyse the results of multiple studies together, in a type of study called a systematic review. Even better is to consider the results of several of these systematic reviews together. In 2021, one such study was performed, including 8 different systematic reviews including a total of 62 randomised controlled trials (the best quality of scientific clinical study).¹⁰ The following were found in some but not all studies:¹⁰

• ESWT was more effective than a “sham” treatment
• Improvements were sustained at periods of 1,3,6, and 12 months following treatment
• ESWT was better for mild and moderate ED than for severe ED
• Several studies showed a combination of phosphodiesterase-5 inhibitor drugs and ESWT was more effective than either treatment alone

So, there is evidence for the effectiveness of ESWT, particularly in mild to moderate ED, and it may be a useful adjunct to phosphodiesterase-5 inhibitor drugs in men who have not responded to drug treatment. Individual studies have shown that in non-responders to phosphodiesterase-5 inhibitors a response may be achieved after ESWT treatment.¹¹ Nevertheless, there is still a need for better quality research and standardisation of the optimum number and intensity of treatments required, as these have varied greatly in studies. 

Of course, the causes of ED are multiple and complex, including physical and psychological factors and in most cases a mix of the two. Like other physical treatments, ESWT has its limitations and a full assessment of the individual causes of ED is still required on a case-by-case basis to achieve optimum treatment.

Currently, in the US the FDA has not approved the use of ESWT as a treatment for erectile dysfunction which is currently considered an experimental treatment, however, it is offered in some centres. In 2021, the Asia-Pacific Society for Sexual Medicine issued a position statement after gathering opinion leaders in ED medicine on the use of ESWT for ED. Essentially, whilst recognising that many studies were promising, it felt that further large trials were needed, particularly in the selection of candidates for treatment and the treatment and dosing schedules used before recommending it as a standard treatment.¹² This seems to echo the position of most expert bodies who determine policy on ED treatment.

A Cochrane review, which is a comprehensive systematic review of available evidence to develop healthcare policy, produced following specific guidelines, is planned for the use of ESWT in ED. The revised protocol for this study was published in 2023, however, it has not yet been completed.¹³

Procedure

ESWT is delivered by a “wand” placed in direct contact with the base and shaft of the penis. Shock waves are heard as loud clicks and produce a physical sensation in the penis. The treatment protocols vary, ranging from 5-6 treatments to 10-12 treatments, with some studies reporting increased effectiveness with a larger number of treatments.¹⁰ Some patients find the procedure uncomfortable, although this can be reduced by the application of a local anaesthetic cream prior to the procedure. The process has an excellent safety profile with few side effects. Some bruising to the shaft of the penis and occasionally infections of the skin can occur.¹¹

Advantages and limitations

Whilst phosphodiesterase-5 inhibitor drugs such as Viagra have revolutionised ED treatment, they essentially treat only the symptoms, rather than the physical causes of ED. Additionally, some men experience side effects, or are unable to take them because of interactions with their regular medications. ESWT as a treatment holds promise in that it can reverse some of the physical changes at the root of ED in many men as an alternative to drug treatment. Another advantage is that phosphodiesterase-5 inhibitors usually need to be taken “on-demand”, in advance of intercourse, whereas ESWT works differently, improving the ability to have spontaneous intercourse. Most studies showing the effectiveness of ESWT have been limited to mild to moderate ED. Severe ED, or ED occurring after radical prostatectomy surgery or radiotherapy for prostate cancer has not been shown to benefit from ESWT.¹⁴ Currently, in the UK, ESWT is not widely available and is not part of the National Institute for Health and Care Excellence (NICE) recommended treatments for ED.

Summary

Extracorporeal shock wave therapy (ESWT) presents a relatively new treatment option for erectile dysfunction for cases in which poor penile blood flow is a significant problem. Whilst phosphodiesterase-5 inhibitor drugs such as Viagra are still the mainstay of treatment, ESWT offers a non-pharmacological approach to treatment which is well tolerated, with minimal side effects. Thought to work by promoting the growth of new blood vessels in the penis, ESWT may work as a stand alone treatment, or in combination with a phosphodiesterase-5 inhibitor like Viagra. Whilst extensive research has been conducted since the technique was first explored in 2010, there is still a need for good quality trials, particularly to provide information on which types of patients with ED are the best candidates for ESWT and the optimum number and intensity of treatments required. Currently, ESWT is not recommended by the Food and Drug Administration (FDA) in the US or NICE in the UK. Nevertheless, a treatment which could potentially reverse some of the vascular changes in certain types of ED with minimal side effects has obvious advantages and may hold promise for the future in the treatment of ED in selected cases. Most expert bodies in erectile dysfunction have suggested that further research is required.