Aimee Rogers, MD
■ Stanley Zaslau, MD, MBA, FACS
■ Introduction
■ Erectile dysfunction (ED) is defined according to the National Institute of Health consensus development panel as the persistent inability to attain and/or maintain an erection sufficient to permit satisfactory sexual intercourse.1
■ The ED must cause some degree of personal distress either to the patient himself or to the couple before treatment should be considered.
■ ED is believed to be a subjective condition.
■ This chapter will review the pathophysiology of ED.
• First, a discussion of the epidemiology and incidence will be presented.
• Next, we will classify erectile dysfunction according to a functional classification.
• Finally, we will review the association of ED to systemic diseases such as diabetes mellitus, hyperlipidemia, atherosclerosis, hypertension, renal failure, and psychogenic causes.
■ Epidemiology
■ One of the most important epidemiological studies on ED is the Massachusetts Male Aging Study.
• In this study, Feldman and colleagues surveyed 1709 men between the ages of 40 and 70 utilizing a self- administered sexual function questionnaire.2
• This random-sample, community-based survey indicated that the overall mean probability of having some degree of sexual dysfunction was 52%. As a man ages
from 40 to 70 years of age, his likelihood of having complete ED triples from approximately 5% to 15%. Also during this time period, the likelihood of having moderate ED doubles from 17% to 34%. However, the likelihood of having mild ED was 17% and remained that way throughout the time period.
• Age was found to be the most important independent predictor of ED. In addition, diabetes mellitus, hypertension, and heart disease were also significant predictors of ED. Interestingly, smoking and alcohol consumption were only weakly correlated with ED.
■ The Olmstead County Study by Panser and colleagues showed similar results between aging and ED.3
• In this study of 2115 men aged 40 to 70 years, the prevalence of ED increased from 12.6% between ages 40 and 49 to 25% between ages 70 and 79. Only 18% of men over the age of 70 were usually able to obtain an erection. Approximately 25% of men over the age of 70 were unable to have an erection at all.
■ Johannes and colleagues evaluated 847 men from the Massachusetts Male Aging Study who were without erectile dysfunction at baseline and had completed the study.4
• Erectile dysfunction was assessed by a self-administered sexual function questionnaire and a single global self-rating question.
• Researchers found that the crude incidence rate for erectile dysfunction was 25.9 cases per 1000 man- years. The annual incidence rate increased with each decade of age and was 12.4 cases per 1000 man-years for men ages 40 to 49, 29.8 for men ages 50 to 59, and 46.4 for men ages 60 to 69.
• The age-adjusted risk of erectile dysfunction was higher for men with lower education, diabetes, heart disease, and hypertension.
■ Classification
■ Many classifications have been proposed for ED. Some systems are based on cause of ED (e.g., diabetes, trauma), while others are based on the neurovascular mechanism of the erectile process (e.g., neurogenic, vasculogenic, arterial, venous).
■ Lizza and colleagues, through the International Society for the Study of Impotence Research, developed a simple classification system for ED. We will discuss this classification system in detail as follows.5
• An outline of the classification system is presented in Table 2.1.
Psychogenic
■ In years past, psychogenic ED was felt to be the most common type.
• In fact, in 1970, Masters and Johnson believed that this represented 90% of cases of ED.6
■ However, at present, researchers believe that most men with ED have a mixed condition, with a predominantly functional component and some secondary associated psychogenic component.
■ In addition, a number of other factors should be considered that contribute to this form of ED, including:
• Deterioration of the relationship between partners
• Job loss
• Loss of partner
• Health problems of patient and partner
■ These problems can lead to anger, hostility, alienation of one’s partner, and/or the partner not being interested in intimacy. Thus, it becomes difficult for a man to obtain a functional erection under these circumstances.
Table 2.1 Classification of Male Erectile Dysfunction
■ Further, life-altering situations, such as death of a spouse, can lead to personal stresses such as guilt, anger, and confusion, which can impair erectile function.
Neurogenic
■ As mentioned previously, erectile function normally requires an intact vascular system and neurological system. Thus, impairment of the neurological system can result in changes in erectile function.
■ As previously discussed, the neural relationships between the brain, spinal cord, and cavernosal nerves are important. As such, diseases in these areas can impair erectile function.
■ At the central nervous system level, numerous diseases such as cerebrovascular accident, Parkinson’s disease, and Alzheimer’s disease can result in ED.
■ As mentioned previously, the dopaminergic nervous system also plays an important role in erectile function. An imbalance in this system caused by dopamine antagonists can impair erectile function, as is often the case in patients with Parkinson’s disease.
■ Spinal cord injury can also result in ED. The type of ED is related to the location of the spinal cord injury.
• Reflexogenic erections are preserved in patients who have lesions of the upper spinal cord.
• However, patients with lumbar or sacral injuries often cannot obtain erections.
• Other spinal cord disease states associated with erectile dysfunction include tumors of the spinal cord, spina bifida, syringomyelia, and multiple sclerosis.
■ One of the most common causes of neurogenic erectile dysfunction occurs after radical prostatectomy due to damage to the cavernosal nerves.
• Finkle and colleagues conducted a retrospective study of 62 patients who underwent radical prostatectomy with normal preoperative erectile function.7
■ Postoperatively, 43% reported normal erections and resumption of sexual intercourse.
■ Preservation of potency after radical prostatectomy is related to several factors, including:
• Age of the patient (younger patients tend to fare better than older patients)
• Preoperative continence status (continent patients tend to fare better than incontinent patients)
• Preservation of the neurovascular bundle (patients with one or both neurovascular bundles spared fare better than patients who have both neurovascular bundles transected).
■ Weinstein and colleagues reported that following abdominoperineal resection, where the entire rectum was extirpated, the effect on sexual functioning differed for men and women.8 Sexual function in men was completely destroyed, while women were capable of continuing sexual enjoyment as before the operation.
• This suggests the importance of the parasympathetic fibers to male erectile function.
■ Erectile dysfunction can also occur after endoscopic surgical procedures to the urethra.
• McDermott and colleagues have shown impotence rates of up to 50% after cold knife urethrotomy procedures.9
■ Pelvic fracture can result in ED due to pelvic and caver- nosal nerve injury.
• This can result from posterior urethral disruption because in this setting, injury to the puboprostatic ligament can dislodge the prostate from the posterior urethra.
• This same force can result from cavernosal nerve injury. Patients can have ED after urethroplasty as a result of both the initial injury and the surgical attempt to reconstruct the urethra.
■ Endocrinologic
■ Endocrinologic causes of ED can occur due to hypogonadism, hyperprolactinemia or thyroid disease. Hypogonadism is common in patients with ED.
■ Hypogonadism can be associated with low serum testosterone levels. This condition is associated with:
1. decreased sexual interest
2. decreased frequency of sexual acts
3. decreased frequency of nocturnal erections
■ Granata and associates evaluated the relationship between nocturnal erections and testosterone levels in 201 men. They found that the threshold testosterone level for normal nocturnal erections is approximately 200 ng/dL.10
■ In addition, dysfunction of the hypothalamic-pituitary axis can result in hypogonadism and ED. Disorders such as hypogonadotrophic hypogonadism can be due to tumors or injury.
■ In addition, hypergonotrophic hypogonadism can be due to tumor, testicular injury or viral causes such as mumps orchitis.
■ Hyperprolactinemia can also result in ED. This can be due to pituitary tumors or medications. Patients may present with ED, galactorrhea, gynecomastia and unexplained male infertility.
■ Leonard and colleagues evaluated 1236 consecutive impotent patients and found elevated serum prolactin levels in approximately 6%. These patients also had low levels of serum testosterone.11
■ Patients with hyperthyroidism can also have ED. Symptoms of hyperthyroidism include decreased libido, which is often associated with increased serum estrogen levels.
■ On the other hand, patients with hypothyroidism often have low serum testosterone and elevated prolactin levels. Thus, both thyroid hyper- or hypo-functioning states can be associated with ED.
■ Arteriogenic
■ Arteriogenic ED can be due to a variety of reasons including trauma to the hypogastric, cavernosal, or helicine arteries or due to atherosclerotic disease. These diseases result in decreased penile perfusion.
■ Risk factors for arterial insufficiency include:
1. hypertension
2. hyperlipidemia
3. cigarette smoking
4. diabetes mellitus
5. blunt perineal or pelvic trauma
6. pelvic irradiation
■ Arteriography studies, although not commonly performed, indicate some important findings: Patients with atherosclerosis typically have diffuse bilateral disease of the internal pudendal, common penile, and/or cavernosal arteries.
■ Levine and colleagues reviewed the results of 24 male patients with blunt pelvic or perineal trauma who developed immediate impotence. This group found that blunt pelvic trauma was associated with a higher incidence of the distal internal or common penile artery injuries.12
■ Ruzbarsky and colleagues did postmortem studies of the arterial bed in 15 male diabetics. They found fibrous proliferation of the intima, medial fibrosis, calcification, and narrowing of the lumen to obilteration from thrombi. The extent of the pathology was apparently related to both age and diabetes mellitus. This certainly explains the high incidence of ED in this population.13
■ Finally, ED and cardiovascular disease share the same risk factors such as hypertension, diabetes mellitus, hypercholesterolemia and smoking. As such, ED can be a presenting or accompanying symptom in these conditions.
■ Vasculogenic
■ Venogenic erectile dysfunction results from a variety of reasons including failure of the veno-occlusive mechanism. The following mechanisms further explain this dysfunction:
1. Dilation of the venous channels in the corpora cavernosa
2. Inadequate compression of the emmissary veins due to underlying disease. Example:
Peyronie’s Disease due to the fibrous scarring of the tunica albiguinea can prevent adequate emissary vein closure.
3. Smooth muscle dysfunction within the cavernosal vasculature can lead to venous leakage. This can be associated with impaired nitric oxide release and impair corporal smooth muscle relaxation.
4. Patients who have a history of priapism and had undergone an arterio-venous shunt will have presistent venous leakage due to this prior shunt.
■ There are four components of venogenic ED to consider further:
• Fibroelastic component
• Smooth muscle
• Gap junctions
• Endothelium
■ The fibroelastic component. With development of diseases such as diabetes, hypercholesterolemia and aging, there is loss of compliance of the penile sinusoids. Collagen deposition occurs.
■ The smooth muscle component. Relaxation of corporal smooth muscle leads to erection. Thus, conditions which damage the corporal smooth muscle will be associated with erectile dysfunction. Thus, patients with diabetes have damage to the vascular smooth muscle in the cavernosal tissues. This smooth muscle disease has micro level dysfunction as well. Alteration of normal ion channels can occur. Specifically, deficits in ion transport of potassium and calcium are likely. Because of these deficits, altered smooth muscle calcium homeostasis occurs leading to impaired relaxation of the caver- nosal smooth muscle tissue in patients with ED.
■ The gap junction component. The gap junctions are responsible for communication between cells and plays an important role in the regulation of the normal erectile process. It is possible that in patients with severe vascular disease that normal caverno- sal cells lose their ability to contact each other because of the fibrosis that develops between cells. This can lead to a lack of coordinated relaxation of cavernosal smooth muscle cells.
■ The endothelial component. The normal endothelium functions to promote erections and flaccidity through the release of prostglandins, endothelins and nitric oxide. This is due to mediation through the cholinergic and adrenergic nervous systems. Various disease states have been known to impair nitric oxide release and endothelium-mediated relaxation of the cavernosal smooth muscle tissue. Impairment of this mechanism occurs in diabetes and hypercholesterolemia.
■ Conclusions
■ Practitioners should remember that many classifications have been proposed for ED. Some systems are based on cause of ED (e.g., diabetes, trauma), while others are based on the neurovascular mechanism of the erectile process (e.g., neurogenic, vasculogenic, arterial, venous).
■ There are many conditions that can contribute to ED. These can be organic and/or psychologic.
■ Our understanding of the development and treatment of ED continues to evolve.
■ References
1. NIH consensus development panel on impotence. JAMA. 1993;27:83-90.
2. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychological correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54-61.
3. Panser LA, Rhodes T, Girman CJ, et al. Sexual function of men age 40 to 79 years: the Olmstead County Study of Urinary Symptoms and Health Status Among Men. J Am Geriatr Soc. 1995;43(10):1107—1110.
4. Johannes CB, Araujo AB, Feldman HA, et al. Incidence of erectile dysfunction in men ages 40-69: longitudinal results from the Massachusetts Male Aging Study. J Urol. 2000;163:460.
5. Lizza EF, Rosen RC. Definition and classification of erectile dysfunction: report of the Nomenclature Committee of
the International Society of Impotence Research. Int J Impot Res. 1999;11:141.
6. Masters W, Johnson V. Human Sexual Response. Boston, MA: Little-Brown; 1970.
7. Finkle AL, Taylor SP. Sexual potency after radical prostatectomy. J Urol. 1981;125:350.
8. Weinstein M, Roberts M. Sexual potency following surgery for rectal carcinoma. A follow-up of 44 patients. Ann Surg. 1977;185:295.
9. McDermott DW, Bates RJ, Heney NM, et al. Erectile impotence as a complication of direct vision cold knife urethrotomy. Urology. 1981;18:467.
10. Granata AR, Rochira V, Lerchl A, et al. Relationship between sleep-related erections and testosterone levels in men. J Androl. 1997;18:522-527.
11. Leonard MJ, Nickel CJ, Morales A. Hyperprolactinemia and impotence: why, when and how to investigate. J Urol. 1989;142:992-994.
12. Levine FJ, Greenfield AJ, Goldstein I. Arteriographically determined occlusive disease within the hypogastric-cavernous bed in impotent patients following blunt and perineal and pelvic trauma. J Urol. 1990;144:1147-1153.
13. Ruzbarsky V, Michal V. Morphological changes in the arterial bed of the penis with aging. Relationship to the pathogenesis of impotence. Invest Urol. 1977; Nov 15(3):194—199.