ERECTILE DYSFUNCTION (ED)

• ACRONYMS AND DEFINITIONS

• ED - Erectile dysfunction
• RCT - Randomized controlled trial

• PREVALENCE

• In studies, erectile dysfunction prevalence has varied widely, depending on the population surveyed and the definition used. The table below shows typical ranges reported in surverys from around the world.

• PHYSIOLOGY OF AN ERECTION

• The corpora cavernosa of the penis contains a network of smooth muscle cells, endothelial cells, and sinusoid cavities
• An erection begins when endothelial cells are stimulated, causing them to release nitric oxide, which relaxes smooth muscle cells
• Smooth muscle cell relaxation allows the sinusoids to dilate and fill with blood
• Engorged sinusoids compress veins, inhibiting blood flow out of the penis [1,2,3]

• RISK FACTORS

• Overview
• While it may seem like a simple function, the formation of an erection is actually quite complex, relying on the interplay of psychologic, neurologic, endocrinologic, and vascular processes. Issues with one or a combination of these systems can cause ED.
• Risk factors for ED grouped by etiology are presented in the table below

• MEDICATIONS ASSOCIATED WITH ERECTILE DYSFUNCTION

• A number of medications have been associated with erectile dysfunction
• Evidence for a causal relationship is weak in some cases. For example, blood pressure medications have been associated with erectile dysfunction, but they are mostly used in individuals who have other risk factors, so their overall contribution to ED is difficult to discern.
• Some medications have a definitive causal relationship (ex. antidepressants)

• ED WORKUP

• Guidelines from the American Urological Association and the European Association of Urology recommend that labs and diagnostic studies be patient-specific and guided by physical exam and history findings
• The table below lists some specific findings and their possible associations

• TESTOSTERONE AND ED

• Testosterone levels and ED symptoms
• Testosterone plays an important role in erectile function. That being said, it appears that testosterone-related erectile dysfunction only occurs at very low levels.
• A European study that included over 2800 men measured the correlation between testosterone levels and self-reported sexual function. The study found that sexual function improved with increasing testosterone only in the range of 0 - 230 ng/dl. The effect plateaued at 230 ng/dl, and no improvement was seen at higher levels. [PMID 21849522]

• Testosterone replacement and ED symptoms
• A number of small studies have evaluated the effect of testosterone replacement on ED symptoms. Results from these studies have been inconsistent across a wide range of patient populations (see testosterone and sexual function studies). In studies that only included patients with low testosterone levels, testosterone replacement had no clear effect on ED symptoms.
• Studies that evaluated the addition of testosterone therapy to phosphodiesterase inhibitors (e.g. Viagra, Cialis) have also found no clear benefit of adding testosterone to these drugs [7,8,9]

• TREATMENT OF ED

• Lifestyle modification
• Weight loss and exercise
• A randomized, controlled trial published in 2004 clearly showed that weight loss and exercise improve ED symptoms. In the same study, weight loss and exercise were also shown to improve the physiologic processes involved in erection formation (response to nitric oxide). See ED weight loss study below.
• Overweight, sedentary patients with ED should be encouraged to exercise and lose weight to improve their ED symptoms
• Smoking cessation
• Smoking cessation has been associated with improved ED symptoms and a lower incidence of ED
• Smokers should be encouraged to quit

• Phosphodiesterase type 5 inhibitors (PDE-5I)
• Phosphodiesterase type 5 inhibitors (ex. Viagra®, Cialis®) have become the overwhelming preferred treatment for ED
• In clinical trials, PDE-5Is improve erectile function in ≥ 50% of patients when compared to placebo
• PDE-5Is have been shown to be effective in treating ED across all types of etiologies including vascular, neurologic, psychogenic, s/p prostatectomy, and medication-induced
• All PDE-5Is appear to be equally effective, and no meaningful head-to-head trials have been performed [1,3]
• See erectile dysfunction medications for a review of PDE-5Is

• Penile injections and suppositories
• Prior to PDE-5Is, alprostadil in the form of a penile injection (Caverject®) or penile urethral suppository (Muse®) was the primary medication used to treat ED
• Alprostadil has largely been replaced by PDE-5Is, but may still be used in patient who do not respond to PDE-5Is
• Alprostadil penile injections are effective in > 70% of patients. Alprostadil suppositories are effective in 30 - 66% of patients.
• The inconvenience of these methods hinder their acceptance with patients [1,3]
• See erectile dysfunction medications for a review of penile injections and suppositories

• Penile implants
• Penile implants (also called penile prostheses) are available for the treatment of ED
• Some implants are semi-rigid, and some are inflatable with a scrotal pump
• While these treatments are typically reserved as a last resort, patient satisfaction rates are high (70 - 90%) [1,3]

• Other
• Vacuum devices - vacuum devices suck blood into the penis and then a constrictor ring is placed at the base of the penis to retain the blood. Patient satisfaction with these devices varies widely (27 - 94%). Side effects include pain, inability to ejaculate, bruising, and numbness. Discontinuation rates are high (≥ 50%). [1,3]
• Shockwave therapy - low intensity extracorporeal shock wave therapy has been shown to be effective in some small studies. This therapy is not widely available. [PMID 22425129]

• ERECTILE DYSFUNCTION STUDIES

• BIBLIOGRAPHY

• 1 - PMID 23040455 - Lancet review
• 2 - PMID 18077811 - NEJM review
• 3 - European Assoc of Urology Guidelines on Male Sexual Dysfunction, 2014
• 4 - PMID 20388160 - ED prevalence study
• 5 - PMID 18664536 - Risk factors for low T
• 6 - PMID 21849522 - Correlation between levels and symptoms
• 7 - PMID 20525905 - Endocrine Soc male hypogonadism GL 2010
• 8 - PMID 24978674 - Trial of T replacement in diabetics
• 9 - PMID 23165659 - Testosterone added to viagra
• 10 - PMID 20112889