Conventional Treatment Of Erectile Dysfunction
Phosphodiesterase-5 (PDE5) Inhibitors
The signaling molecule cyclic guanosine monophosphate (cGMP) is an important mediator of vasodilatation, penile blood flow, and therefore erection. The natural destruction of cGMP by the phosphodiesterase-5 (PDE5) enzyme effectively shuts down the erection process, returning the penis to its non-erect (flaccid) state (Kolodny 2011).
Medications used to treat erectile dysfunction, such as sildenafil (Viagra®), vardenafil (Levitra®), and tadalafil (Cialis®), improve erectile function by inhibiting the PDE5 enzyme, allowing an erection to persist (Kolodny 2011). However, approximately one-third of men with erectile dysfunction do not respond to PDE5 inhibitors (Heidelbaugh 2010). Men whose erectile dysfunction is not improved by PDE5 inhibitors may have low testosterone levels and should have a testosterone blood test (Nehra 2012).
Although PDE5 inhibitors are generally well tolerated, they can cause a number of side effects including headache, indigestion, visual disturbances, priapism (ie, painful, prolonged erection lasting more than 6 hours), and even blindness (Stroberg 2006; Rashid 2005; Burnett 2011; Wolfe 2005). Furthermore, the use of PDE5 inhibitors is limited in some men by contraindications such as cardiovascular disease. These drugs can also interact with other medications (eg, nitrates) and cause negative reactions (Rashid 2005; Burnett 2011; Wolfe 2005; Heidelbaugh 2010). PDE5 inhibitors only improve erectile function, not overall sexual function (Heidelbaugh 2010).
In men who are not good candidates for or do not respond well to PDE5 inhibitors, intracavernosal vasodilating medications are a second-line treatment option. These treatments are delivered via self-injection into the cavernosum. Adverse effects may include pain, prolonged erection, and fibrosis (MD Consult 2009a,b; MD Consult 2010).
- Alprostadil. Alprostadil is synthetic prostaglandin E1, which is a biochemical signaling molecule with vasodilatory properties (Lea 1996; Costabile 2008). Studies show alprostadil to be effective in about 70% of men with erectile dysfunction (Lea 1996). Alprostadil can now be delivered via topical cream as well, which has demonstrated a success rate similar to injectable forms (Rooney 2009; MD Consult 2012a).
- Papaverine. Papaverine, a compound derived from the poppy plant, nonspecifically inhibits phosphodiesterase enzymes and modulates calcium signaling. It does not possess opiate properties like some other poppy derivatives such as morphine. Studies suggest a patient satisfaction rate of about 44%. Papaverine use may increase liver function tests with the potential for hepatotoxicity (Pinsky 2010).
- Phentolamine. Phentolamine blocks alpha-1 and -2 adrenergic receptors. This helps facilitate erection by impairing muscle constriction. Phentolamine alone is not sufficient to trigger and sustain rigid erection, so it is used in combination with other intracavernosal agents for an additive effect. Because phentolamine is expensive and needs to be refrigerated, it may be less convenient (Pinsky 2010).
Vacuum Erection Devices (VEDs)
Another alternative is utilizing a vacuum device to artificially increase penile blood flow. These devices consist of plastic cylinders that are placed over the penis and vacuumed by a pump to negative pressure to allow cavernosal expansion and erection. Constriction rings are then placed at the base of the penis to retain blood. Vacuum erection devices provide a relatively safe and efficacious alternative for those unresponsive to or unable to take oral medications. Disadvantages include lack of penile stability, which may interfere with sexual performance, and inhibited ejaculation (Pinsky 2010).
Erectile function and overall sexual satisfaction can be considerably impacted by psychological and interpersonal factors. Evidence suggests a psychogenic contribution to as many as 40% of erectile dysfunction cases. Psychosocial variables such as anxiety about seeking erectile dysfunction treatment undermine availability of effective treatment options as well. A comprehensive review conducted in 2008 showed that group psychotherapy can significantly improve erectile dysfunction and complement pharmacologic treatment strategies (Melnik 2008).
Shock Wave Therapy
Extracorporeal ultrasound shock wave therapy is used to treat some penile disorders such as Peyronie’s disease (Palmieri 2012; MD Consult 2012b). Application of low-intensity ultrasound shock waves to the penis is emerging as a treatment for erectile dysfunction among men without other penile disorders. In a pioneering, randomized, double-blind, sham-controlled study on 67 men, researchers showed that shock wave therapy significantly improved erectile function and penile blood flow among previous responders to PDE-5 inhibitors. Treatment was well tolerated with none of the subjects reporting discomfort or adverse events (Vardi 2012). Another study showed that shock wave therapy improved erectile function in 29 men who responded poorly to PDE5 inhibitors (Gruenwald 2012).