Upon completion of the chapter, the reader will be able to:
Explain the pathophysiology of erectile dysfunction (ED).
Recognize risk factors and medications associated with the development of ED.
Identify the goals of therapy when treating ED.
Describe current nonpharmacologic and pharmacologic options for treating ED, and determine an appropriate first- and second-line therapy for a specific patient.
Identify patients with significant cardiovascular risk and recommend an appropriate treatment approach for their ED.
Compare and contrast the benefits and risks for the current phosphodiesterase type 5 (PDE5) inhibitors.
Assess reasons for PDE5 failure and determine an optimal approach to improve treatment efficacy.
Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection sufficient for sexual intercourse. ED is the most prominent sexual problem in men, and it can lead to lower quality of life and self-esteem.1 Patients may also develop libido or ejaculatory disorders, but these are not considered ED.
EPIDEMIOLOGY AND ETIOLOGY
ED increases with age. Few men report erection problems before age 40, but ED increases to 61% in men aged 40 to 69 years and 77% in men older than 70 years.2 The increase in incidence could be due to physiologic changes that occur with aging, the onset of chronic disease states associated with ED, increased medication use, lifestyle factors, or a combination of the above.
The penis consists of three components, two dorsolateral corpora cavernosa and a ventral corpus spongiosum that surrounds the penile urethra and distally forms the glans penis.
In the flaccid state, a balance exists between blood flow into and out of the corpora cavernosa. With sexual stimulation, nerve impulses from the brain travel down the spinal cord triggering a reduction in sympathetic tone and an increase in parasympathetic activity. This leads to an increased production of nitric oxide (NO), which enhances the activity of guanylate cyclase. This results in increased production of cyclic guanosine monophosphate (cGMP). The enzyme phosphodiesterase type 5 (PDE5) is responsible for the catabolism of cGMP within the cavernosal tissue. Vasoactive peptide and prostaglandins E1 and E2 stimulate increased production of cyclic adenosine monophosphate (cAMP). Both cAMP and cGMP reduce calcium concentrations within smooth muscle cells of the penile arteries and the sinusoidal spaces, leading to smooth muscle relaxation and increased blood flow. As the spaces become engorged, pressure increases, subtunical venules are compressed by the tunica albuginea, and the penis becomes rigid and elongated (Figure 51–1).
Molecular mechanism of penile smooth muscle relaxation. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), activate their specific protein kinases, which leads to sequestration of intracellular calcium by the endoplasmic reticulum. The resultant decrease in intracellular calcium leads to smooth muscle relaxation. Sildenafil inhibits the action of phosphodiesterase (PDE) ...