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LEARNING OBJECTIVES

LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

  1. Explain the pathophysiology of erectile dysfunction (ED).

  2. Recognize risk factors and medications associated with the development of ED.

  3. List the goals of therapy when treating ED.

  4. Describe current nonpharmacologic and pharmacologic options for treating ED, and determine appropriate first- and second-line therapies for a specific patient.

  5. Identify patients with significant cardiovascular risk and recommend an appropriate treatment approach for their ED.

  6. Identify contraindications for the use of phosphodiesterase type 5 (PDE5) inhibitors.

  7. Compare and contrast the benefits and risks for current PDE5 inhibitors.

  8. Assess reasons for PDE5 failure and determine an optimal approach to improve treatment efficacy.

INTRODUCTION

Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain an erection sufficient for sexual intercourse.1 ED is the most prominent sexual disorder in men and can lead to lower quality of life and self-esteem.2 Other male sexual complaints include libido and ejaculatory disorders, but these are not considered ED.

EPIDEMIOLOGY AND ETIOLOGY

The incidence of ED increases with age. Few men report erection problems before age 40, but one study reported rates as high as 61% in men aged 40 to 69 years and 77% in men older than 70 years.3 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.

PATHOPHYSIOLOGY

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. The corpora are composed of sinusoidal spaces that are encased in a fibrous sheath called the tunica albuginea.

In the flaccid state, a balance exists between blood flow into and out of the corpora cavernosa. Sexual stimulation triggers a reduction in sympathetic tone and an increase in parasympathetic activity. This stimulates the release of nitric oxide (NO), which in turn enhances the production of cyclic guanosine monophosphate (cGMP). The enzyme phosphodiesterase type 5 (PDE5) is responsible for the catabolism of cGMP within the cavernosal tissue. Prostaglandins, E1 and E2, stimulate increased production of cyclic adenosine monophosphate (cAMP). Increased cAMP and cGMP concentrations ultimately lead to smooth muscle relaxation and increased blood flow into the cavernosal spaces. As the spaces become engorged, pressure increases, subtunical venules (very small veins) are compressed by the tunica albuginea, and the penis becomes rigid and elongated (Figure 51–1).

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 ...

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