Background:

Erectile dysfunction (ED), a sexual disorder consisting of penile rigidity which is inadequate for satisfactory sexual intercourse, currently affects up to 50% of 40 to 70 year old men. Erectile dysfunction affects more than 150 million men throughout the world.  There are many possible causes of erectile dysfunction including anxiety, depression, neurologic causes, cardiovascular disease, hypertension, diabetes, elevated cholesterol, pelvic trauma, and renal disease. Men who have had pelvic surgery such as radical prostatectomy, or radiation require a specialized regimen of penile rehabilitation which includes oral medication and penile injection therapy for a specific time course. Multiple US and international consensus medical groups (i.e., World Health Organization, International Consultation on Urological Diseases, American Urological Association, Societe d’Urologie, International Society for Sexual Medicine) have now recognized the public health significance of sexual function and dysfunction.  Workup includes a thorough history and physical examination to obtain information to identify possible causes of ED.  Indicated lab testing and in certain cases penile doppler ultrasound to evaluate penile bloodflow are completed.  Questionnaires such as the gold standard International Index of Erectile Function (IIEF-5) are used to classify severity of ED and scores can be calculated online.

How does a normal erection work?

Erection is a carefully conducted “orchestra” including complex interaction between arteries, veins, nerves.  Erection normally starts with sexual arousal, which stimulates nitric oxide (NO) release from penile nerve endings and vascular endothelial cells. NO diffuses into vascular smooth muscle cells in the penile corpus cavernosum leading to elevation of a molecule, called cyclic guanosine monophosphate (cGMP), in these cells. This process leads to activation of multiple proteins (cGMP dependent protein kinase) and ultimately lowering of cell calcium, finally leading to smooth muscle relaxation. Increased accumulation of blood in the corpus cavernosum from this relaxation is the foundation for penile erection. Lack of proper cGMP elevation and NO release could be at least a partial of erectile dysfunction. PDE5 inhibtors inhibit PDE5, which is an enzyme that degrades cGMP. Decreased degradation of cGMP increases relaxation of the smooth muscle, which dilates the corporeal sinusoids, resulting in increased blood flow and facilitates erection.

Treatment options for Erectile Dysfunction:

For appropriate candidates, there are four possible ED treatment options including oral medication, vacuum erectile device (VED), penile injection therapy/intraurethral suppositories, and penile prosthesis insertion accoding to the International Congress of Sexual Medicine Summary.  Changes in diet to improve cardiovascular disease, obesity, and diabetes risk may be beneficial including cholesterol changes.  Medications aimed at improving these conditions may also benefit erectile function, including use of statin cholesterol-lowering medications to improve erectile function in addition to cardiovascular issues. Oral therapy available in the United States includes phosphodiesterase-5 inhibitors (PDE5i) such as sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis), and avanafil (Stendra). There are some differences between the medications in terms of onset of action and side effects. PDE5i medication may be combined with other therapy (VED for example) in some cases to improve response. PDE5i medications are effective by causing smooth muscle relaxation. Erection normally starts with sexual arousal, which stimulates nitric oxide (NO) release from penile nerve endings and vascular endothelial cells. NO diffuses into vascular smooth muscle cells in the penile corpus cavernosum leading to elevation of a molecule, called cyclic guanosine monophosphate (cGMP), in these cells. This process leads to activation of multiple proteins (cGMP dependent protein kinase) and ultimately lowering of cell calcium, finally leading to smooth muscle relaxation. Increased accumulation of blood in the corpus cavernosum from this relaxation is the foundation for penile erection. Lack of proper cGMP elevation and NO release could be at least a partial of erectile dysfunction. PDE5 inhibtors inhibit PDE5, which is an enzyme that degrades cGMP. Decreased degradation of cGMP increases relaxation of the smooth muscle, which dilates the corporeal sinusoids, resulting in increased blood flow and facilitates erection. Injection therapy includes a cocktail of vasoactive medications such as alprostadil, papaverine, and phentolamine (called Trimix) which are injected intracavernosally.  Alternatively, non-injectable therapy includes intraurethral alprostadil suppository (pellet placed into urethral meatus). For medical-refractory erectile dysfunction such as men with severe venous leak, penile prosthesis insertion (semi-rigid without pump, or inflatable with pump mechanism) may be indicated.

The Future of Erectile Dysfunction Treatment:

Research including biological reconstruction and other tissue engineering with nanoparticles (containing nitric oxide for example) is underway in animal studies.  Very preliminary studies of endovascular procedures for vasculogenic disease leading to ED are underway to facilitate bloodflow in internal pudendal artery. Additional early work on embolization of the dorsal penile vein for men with veno-occlusive dysfunction is in progress.  New modifications of oral medication and penile prostheses are also on the horizon.

We are pleased to discuss erectile dysfunction workup further with you.  Please contact us for additional information and to schedule a consultation.

Matthew Wosnitzer, M.D.