madman
Super Moderator
Physiology of Erection and Pathophysiology of Erectile Dysfunction (2021)
Susan M MacDonald, Arthur L Burnett
INTRODUCTION
The complex pathway from sexual arousal to penile erection has been elucidated in great detail. Advances in neuroimaging have delineated the cortical and limbic system involvement in erections. The molecular biology underlying erections has been expanded on, identifying several potential therapeutic targets. Furthermore, the intricate interplay of molecular biology and physiology underlying erectile dysfunction (ED) has been associated with common medical comorbidities, such as cardiovascular disease and diabetes. This article discusses advances in the science of erections and the pathophysiology associated with their dysfunction.
*PHYSIOLOGY OF PENILE TUMESCENCE AND DETUMESCENCE
At baseline, the penis is primarily under sympathetic tone and flaccid. The smooth muscle within the cavernosal sinusoids and the penile arteries is tonically contracted, maintaining the unerect state. This sympathetic tone is mediated by the release of noradrenaline, which maintains flaccidity for 23 hours a day, on average.1 In response to sexual stimulation, a series of physiologic changes occur—the stages of tumescence:
1. Sexual or tactile stimulation leads to a release of nitric oxide (NO) from the cavernous nerves that induce smooth muscle relaxation. This relaxation results in the dilation of arterioles and arteries within the corpora cavernosa.2
2. Blood accumulates within the cavernosal sinusoids, which compress the subtunical venous plexus and decreases venous outflow (latent phase).
3. Expansion of the corpora cavernosa stretches the tunica albuginea. The emissary veins draining the corporal bodies are compressed between the inner circular and outer longitudinal layers of the tunica albuginea (tumescent phase).
4. Intracavernosal pressure (up to 100 mm Hg) and oxygen content (up to 90 mm Hg) increase as blood is trapped in the corpora and penile erection occurs (full erection phase).
5. Intracavernosal pressure is increased further with contraction of the ischiocavernosus and bulbocavernosus muscles, leading to glans engorgement and a rigid erection, which can be associated with suprasystolic intracorporal pressures (rigid phase).
The process of detumescence occurs when sexual stimulation resolves or after orgasm; detumescence has been studied in canine models and a similar process is thought to mediate loss of erection in humans3 :
1. Intracavernosal pressure transiently rises as cavernous arteries vasoconstrict due to smooth muscle cell contraction.
2. Intracavernosal pressure decreases slowly as arterial inflow returns to baseline and venous outflow begins.
3. Rapid intracavernosal pressure decreases (80% overall pressure) due to decompression of the emissary veins and full restoration of venous outflow.
*CORPUS SPONGIOSUM AND GLANS PENIS
TYPES OF ERECTIONS
Penile erection may be induced by several stimuli, both external and internal. Broadly speaking, erections are classified into 3 types, which are not necessarily mutually exclusive:
Psychogenic—triggered by auditory, visual, or nongenital tactile stimulation that involves cortical processing of the stimulus as erotic. This type of erection is mediated by cortical inhibition of sympathetic tone from the spinal cord and may be preserved in patients with lower spinal cord injury (ie, below T11).4
Reflexogenic—triggered by tactile stimulation of the genitals via a reflex arc through the autonomic nuclei to the cavernous nerves. Reflexogenic erections typically are maintained in patients with upper spinal cord injury (ie, above T11).4
Nocturnal—occur involuntarily, primarily during rapid eye movement sleep
*NEUROANATOMY OF AN ERECTION
Cortex to Spinal Cord
In summary, activation of the cerebral cortex appears to occur with processing tactile stimulation to the penis (paracentral lobule) or audiovisual stimuli (inferior temporal lobes bilaterally). Areas of the limbic system that appear to be involved in the contextual or emotional processing of these stimuli and the motivation to act on them. Impulses then travel to the spinal erection centers (T11-L2 and S2-4) to activate the initiation of a psychogenic erection through the peripheral nerves (Fig. 1).
Spinal Cord to the Peripheral Nerves
Within the spinal cord, 3 types of neurons travel to the genitalia to coordinate erection and ejaculation: sympathetic (thoracolumbar), parasympathetic (sacral), and somatic (motor and sensory) (Fig. 2).18
Autonomic pathway
*Sympathetic
*Parasympathetic
Somatic pathway
*Motor
*Sensory
*MOLECULAR MECHANISM
*PATHOPHYSIOLOGY OF ERECTILE DYSFUNCTION
Introduction
ED often is the end result of multiple pathophysiologic processes. Once a man has experienced ED, it is impossible to rule out at least some psychological component, given the anxiety-provoking nature of the disease. Although classification schemes differ, for the purposes of this article, conditions known to be associated with organic ED are grouped into vasculogenic, neurogenic, and hormonal categories (Fig. 5).28
Vasculogenic
Arteriogenic (arterial insufficiency)
ED categorized as “arteriogenic” is due to diminished arterial inflow and thus decreased perfusion pressure. This manifests as decreased maximal rigidity and delayed time to a full erection. The etiology of arteriogenic ED may be atherosclerotic disease or trauma to the hypogastric cavernous-helicine arterial tree. In young patients with a history of blunt pelvic or perineal trauma, focal stenosis of the common penile or cavernosal artery may be the etiology.32 Arteriogenic ED, which accounts for a majority of cases, has been strongly linked to the following conditions:
hypertension, hyperlipidemia, tobacco use, metabolic syndrome/obesity, sedentary lifestyle, diabetes, and pelvic radiation.33–38 Doppler ultrasound has been used to correlate decreased peak systolic velocity of the cavernosal arteries with underlying vascular disease and risk of cardiovascular events.39,40
The pathologic mechanism underlying arteriogenic ED is likely multifactorial, including 1 or more of the following, as suggested by Musicki and colleagues41 in a 2015 review: (1) endothelial dysfunction, (2) smooth muscle alterations, (3) autonomic dysregulation (discussed later), (4) hypogonadism (see endocrine section), and (5) metabolic defects. Endothelial dysfunction typically is described as decreased reactivity to vasodilators or increased reactivity to vasoconstrictors; other factors, such as oxidative stress, may play a role. Hypercholesterolemia-induced atherosclerosis in the penis is associated with endothelial dysfunction as indicated by reduced NO production, impaired relaxation in response to muscarinic stimulation, and increased lipid peroxidation.42 Diabetes manifests such changes as decreased nNOS expression, reduced eNOS activity, reduced vascular endothelial growth factor release, and increased reactive oxygen species production in the corpora cavernosa in animal models.43
*Alterations of vascular smooth muscle content and function have been suggested as contributing factors to ED.
Cavernosal dysfunction
ED due to cavernosal dysfunction is the inability to maintain adequate vascular tension for a rigid erection due to a variety of structural defects including enlarged veins, fibrosis, increased smooth muscle tone, or impaired sinusoidal endothelial-dependent relaxation. Previously, this category was referred to as venous leak; however, this term did not adequately encompass the wide array of ultrastructural changes that lead to ED. Large congenital or ectopic superficial dorsal, deep dorsal, or crural veins may elevate end-diastolic velocity or outflow.45,46 More commonly, fibrosis of the tunica albuginea and/or corpora (as in Peyronie disease or other scar tissue conditions) leads to insufficient compression of the emissary veins. Inadequate relaxation of the trabecular smooth muscle due to decreased fibroelasticity or increased adrenergic tone, as well as persistent venous shunts (eg, related to prior treatment of priapism) also may cause cavernosal dysfunction.44 Animal models of diabetes have demonstrated significantly less smooth muscle contractility via decreased mRNA and protein expressions of smooth muscle a-actin and M myosin heavy chain required for function in cavernosal tissue.47 A 50% decrease in the maximal contraction of cavernosal smooth muscle was demonstrated at 8 weeks in diabetic rats in response to phenylephrine.48
*The classic history in patients with congenitally enlarged or anomalous venous drainage is an insufficient erection or duration of erection since initial sexual encounters.49
*Penile Doppler ultrasound (PDUS) is a modality utilized more commonly to make a diagnosis of venous leak. Performance of PDUS is dependent on induction of an adequate arterial erection response to characterize end-diastolic velocity accurately.51
Neurogenic
It is difficult to provide a true estimate of neurogenic ED because this category includes a broad range of etiologies at multiple levels of the nervous system. In broad terms, cortical impairment, traumatic injury of the spinal cord, iatrogenic peripheral nerve injury during pelvic surgery, and autonomic dysfunction and/or demyelination due to conditions, such as diabetes, all may be conceptualized as sources of neurogenic ED.
*Cerebral cortex
*Spinal cord
*Peripheral nerves
*Autonomic dysregulation
Endocrine
*Hypogonadism
There is a complex relationship between ED and serum testosterone levels. ED is a well-known potential consequence of androgen deprivation therapy.62 In a population of men with ED ages 25 years to 80 years, 7% were found to have serum testosterone levels less than 200 ng/dL, 23% less than 300 ng/dL, and 33% less than 346 ng/ dL.63 In men with low testosterone, supplementation increases sexual desire and may improve erectile response.64,65 Supplementation of hypogonadal men with testosterone was shown to improve responses to PDE5 inhibitor therapy for ED.66 Further support for the androgen-dependent extent of erectile function includes a threshold testosterone value of 200 ng/dL for regular nocturnal erections.67 In a population of 52 male patients without significant comorbidities who underwent PDUS as part of a work-up for ED, free testosterone levels were associated positively with peak systolic velocity and resistive index and negatively associated with end-diastolic velocity.68 Although the significance is as yet unknown, there may be a locally mediated acute effect of testosterone because levels vary at the time of erection within serum and the corpora cavernosa.69,70
The correlation between low testosterone and decreased erectile function has been studied in animal models to elucidate the physiologic mechanism. In rats castrated for 2 weeks, a prolonged latency period and decreased filling rate of the cavernosa, as well as decreased intracavernosal pressure, were observed.71 Overall, a 50% decrease in erectile response was noted, which was restored with testosterone or dihydrotestosterone (DHT) supplementation.71,72 Dai and colleagues73 demonstrated reduced veno-occlusion in electrically induced erections in castrated rats, which was restored with testosterone supplementation. This effect appeared to be mediated by NO.73 Studies have demonstrated that testosterone and DHT stimulate nNOS gene expression and increase NO in the corpora during erections.72,74 Van den Broeck and colleagues75 confirmed dose-dependent relaxation of human corpora cavernosal tissue with increasing testosterone and DHT.
*Hyperprolactinemia
Hyperprolactinemia results in reproductive as well as sexual dysfunction. Symptoms associated with hyperprolactinemia include loss of libido, ED, galactorrhea, gynecomastia, and infertility. These symptoms typically occur only at severely elevated levels (>35 ng/mL or 735 mU/L).76 Hyperprolactinemia may be idiopathic, drug-induced, secondary to a pituitary adenoma, or related to chronic renal failure.77 Concomitant low testosterone most likely is mediated by prolactin-induced inhibition of gonadotropin-releasing hormone secretion by the pituitary gland.77
*Thyroid dysfunction
Hyperthyroidism or hypothyroidism also may be associated with ED. In a small study of patients with hyperthyroidism and hypothyroidism (71 total patients), 70% and 84% of patients reported at least mild ED, with a Sexual Health Inventory for Men (SHIM) score of less than 21, respectively, compared with 34% of the control group.78 With treatment, statistically significant mean increases in SHIM scores of 7 points in the hyperthyroidism cohort and 8.5 points in the hypothyroidism cohort were noted. 78 Thyroid hormone effects may be mediated by secondary effects on other hormones known to be associated with sexual function. Hypothyroidism is associated with increased serum prolactin and decreased serum testosterone whereas hyperthyroidism is associated with increased estrogen levels.79–81 A direct effect of thyroxine may also be at play in thyroid hormone ED because both alpha and beta thyroxine receptors have been shown to be present in endothelial and smooth muscle cells from human corpora cavernosa.82 Impairment in NO-dependent relaxation of the corpora cavernosa has been reported in animal models of hyperthyroidism.83,84
Psychogenic
Historically, psychogenic issues were thought to be the principal etiology for the vast majority of ED presentations. Pscyhogenic ED may not be a primary etiology in most cases but it is a contributing factor in virtually all cases. There are conflicting data as to whether purely psychogenic ED may be more common among younger patients (<40 years old), with the reported incidence varying from 13% to 83%.85–87 The degree to which ED is psychogenic versus physiologic is difficult to parse out; isolated psychogenic ED is considered a diagnosis of exclusion clinically.
SUMMARY
Advances in neuroimaging and understanding molecular physiology have clarified the biological processes underlying penile erection. This information contributes to the understanding of the scientific basis of ED. Comorbidities that predispose to ED cause concomitant physiologic changes within multiple categories of ED (ie, vasculogenic, neurogenic, endocrine, and psychogenic). An array of disruptions at the molecular (cell signaling and responsiveness to neurotransmitters) and structural (changes in the tunica albuginea, smooth muscle, or vasculature) levels may contribute to ED. Evolving understanding of the science of erections and the pathophysiology of ED helps clinicians guide current and future therapy for patients.
Susan M MacDonald, Arthur L Burnett
INTRODUCTION
The complex pathway from sexual arousal to penile erection has been elucidated in great detail. Advances in neuroimaging have delineated the cortical and limbic system involvement in erections. The molecular biology underlying erections has been expanded on, identifying several potential therapeutic targets. Furthermore, the intricate interplay of molecular biology and physiology underlying erectile dysfunction (ED) has been associated with common medical comorbidities, such as cardiovascular disease and diabetes. This article discusses advances in the science of erections and the pathophysiology associated with their dysfunction.
*PHYSIOLOGY OF PENILE TUMESCENCE AND DETUMESCENCE
At baseline, the penis is primarily under sympathetic tone and flaccid. The smooth muscle within the cavernosal sinusoids and the penile arteries is tonically contracted, maintaining the unerect state. This sympathetic tone is mediated by the release of noradrenaline, which maintains flaccidity for 23 hours a day, on average.1 In response to sexual stimulation, a series of physiologic changes occur—the stages of tumescence:
1. Sexual or tactile stimulation leads to a release of nitric oxide (NO) from the cavernous nerves that induce smooth muscle relaxation. This relaxation results in the dilation of arterioles and arteries within the corpora cavernosa.2
2. Blood accumulates within the cavernosal sinusoids, which compress the subtunical venous plexus and decreases venous outflow (latent phase).
3. Expansion of the corpora cavernosa stretches the tunica albuginea. The emissary veins draining the corporal bodies are compressed between the inner circular and outer longitudinal layers of the tunica albuginea (tumescent phase).
4. Intracavernosal pressure (up to 100 mm Hg) and oxygen content (up to 90 mm Hg) increase as blood is trapped in the corpora and penile erection occurs (full erection phase).
5. Intracavernosal pressure is increased further with contraction of the ischiocavernosus and bulbocavernosus muscles, leading to glans engorgement and a rigid erection, which can be associated with suprasystolic intracorporal pressures (rigid phase).
The process of detumescence occurs when sexual stimulation resolves or after orgasm; detumescence has been studied in canine models and a similar process is thought to mediate loss of erection in humans3 :
1. Intracavernosal pressure transiently rises as cavernous arteries vasoconstrict due to smooth muscle cell contraction.
2. Intracavernosal pressure decreases slowly as arterial inflow returns to baseline and venous outflow begins.
3. Rapid intracavernosal pressure decreases (80% overall pressure) due to decompression of the emissary veins and full restoration of venous outflow.
*CORPUS SPONGIOSUM AND GLANS PENIS
TYPES OF ERECTIONS
Penile erection may be induced by several stimuli, both external and internal. Broadly speaking, erections are classified into 3 types, which are not necessarily mutually exclusive:
Psychogenic—triggered by auditory, visual, or nongenital tactile stimulation that involves cortical processing of the stimulus as erotic. This type of erection is mediated by cortical inhibition of sympathetic tone from the spinal cord and may be preserved in patients with lower spinal cord injury (ie, below T11).4
Reflexogenic—triggered by tactile stimulation of the genitals via a reflex arc through the autonomic nuclei to the cavernous nerves. Reflexogenic erections typically are maintained in patients with upper spinal cord injury (ie, above T11).4
Nocturnal—occur involuntarily, primarily during rapid eye movement sleep
*NEUROANATOMY OF AN ERECTION
Cortex to Spinal Cord
In summary, activation of the cerebral cortex appears to occur with processing tactile stimulation to the penis (paracentral lobule) or audiovisual stimuli (inferior temporal lobes bilaterally). Areas of the limbic system that appear to be involved in the contextual or emotional processing of these stimuli and the motivation to act on them. Impulses then travel to the spinal erection centers (T11-L2 and S2-4) to activate the initiation of a psychogenic erection through the peripheral nerves (Fig. 1).
Spinal Cord to the Peripheral Nerves
Within the spinal cord, 3 types of neurons travel to the genitalia to coordinate erection and ejaculation: sympathetic (thoracolumbar), parasympathetic (sacral), and somatic (motor and sensory) (Fig. 2).18
Autonomic pathway
*Sympathetic
*Parasympathetic
Somatic pathway
*Motor
*Sensory
*MOLECULAR MECHANISM
*PATHOPHYSIOLOGY OF ERECTILE DYSFUNCTION
Introduction
ED often is the end result of multiple pathophysiologic processes. Once a man has experienced ED, it is impossible to rule out at least some psychological component, given the anxiety-provoking nature of the disease. Although classification schemes differ, for the purposes of this article, conditions known to be associated with organic ED are grouped into vasculogenic, neurogenic, and hormonal categories (Fig. 5).28
Vasculogenic
Arteriogenic (arterial insufficiency)
ED categorized as “arteriogenic” is due to diminished arterial inflow and thus decreased perfusion pressure. This manifests as decreased maximal rigidity and delayed time to a full erection. The etiology of arteriogenic ED may be atherosclerotic disease or trauma to the hypogastric cavernous-helicine arterial tree. In young patients with a history of blunt pelvic or perineal trauma, focal stenosis of the common penile or cavernosal artery may be the etiology.32 Arteriogenic ED, which accounts for a majority of cases, has been strongly linked to the following conditions:
hypertension, hyperlipidemia, tobacco use, metabolic syndrome/obesity, sedentary lifestyle, diabetes, and pelvic radiation.33–38 Doppler ultrasound has been used to correlate decreased peak systolic velocity of the cavernosal arteries with underlying vascular disease and risk of cardiovascular events.39,40
The pathologic mechanism underlying arteriogenic ED is likely multifactorial, including 1 or more of the following, as suggested by Musicki and colleagues41 in a 2015 review: (1) endothelial dysfunction, (2) smooth muscle alterations, (3) autonomic dysregulation (discussed later), (4) hypogonadism (see endocrine section), and (5) metabolic defects. Endothelial dysfunction typically is described as decreased reactivity to vasodilators or increased reactivity to vasoconstrictors; other factors, such as oxidative stress, may play a role. Hypercholesterolemia-induced atherosclerosis in the penis is associated with endothelial dysfunction as indicated by reduced NO production, impaired relaxation in response to muscarinic stimulation, and increased lipid peroxidation.42 Diabetes manifests such changes as decreased nNOS expression, reduced eNOS activity, reduced vascular endothelial growth factor release, and increased reactive oxygen species production in the corpora cavernosa in animal models.43
*Alterations of vascular smooth muscle content and function have been suggested as contributing factors to ED.
Cavernosal dysfunction
ED due to cavernosal dysfunction is the inability to maintain adequate vascular tension for a rigid erection due to a variety of structural defects including enlarged veins, fibrosis, increased smooth muscle tone, or impaired sinusoidal endothelial-dependent relaxation. Previously, this category was referred to as venous leak; however, this term did not adequately encompass the wide array of ultrastructural changes that lead to ED. Large congenital or ectopic superficial dorsal, deep dorsal, or crural veins may elevate end-diastolic velocity or outflow.45,46 More commonly, fibrosis of the tunica albuginea and/or corpora (as in Peyronie disease or other scar tissue conditions) leads to insufficient compression of the emissary veins. Inadequate relaxation of the trabecular smooth muscle due to decreased fibroelasticity or increased adrenergic tone, as well as persistent venous shunts (eg, related to prior treatment of priapism) also may cause cavernosal dysfunction.44 Animal models of diabetes have demonstrated significantly less smooth muscle contractility via decreased mRNA and protein expressions of smooth muscle a-actin and M myosin heavy chain required for function in cavernosal tissue.47 A 50% decrease in the maximal contraction of cavernosal smooth muscle was demonstrated at 8 weeks in diabetic rats in response to phenylephrine.48
*The classic history in patients with congenitally enlarged or anomalous venous drainage is an insufficient erection or duration of erection since initial sexual encounters.49
*Penile Doppler ultrasound (PDUS) is a modality utilized more commonly to make a diagnosis of venous leak. Performance of PDUS is dependent on induction of an adequate arterial erection response to characterize end-diastolic velocity accurately.51
Neurogenic
It is difficult to provide a true estimate of neurogenic ED because this category includes a broad range of etiologies at multiple levels of the nervous system. In broad terms, cortical impairment, traumatic injury of the spinal cord, iatrogenic peripheral nerve injury during pelvic surgery, and autonomic dysfunction and/or demyelination due to conditions, such as diabetes, all may be conceptualized as sources of neurogenic ED.
*Cerebral cortex
*Spinal cord
*Peripheral nerves
*Autonomic dysregulation
Endocrine
*Hypogonadism
There is a complex relationship between ED and serum testosterone levels. ED is a well-known potential consequence of androgen deprivation therapy.62 In a population of men with ED ages 25 years to 80 years, 7% were found to have serum testosterone levels less than 200 ng/dL, 23% less than 300 ng/dL, and 33% less than 346 ng/ dL.63 In men with low testosterone, supplementation increases sexual desire and may improve erectile response.64,65 Supplementation of hypogonadal men with testosterone was shown to improve responses to PDE5 inhibitor therapy for ED.66 Further support for the androgen-dependent extent of erectile function includes a threshold testosterone value of 200 ng/dL for regular nocturnal erections.67 In a population of 52 male patients without significant comorbidities who underwent PDUS as part of a work-up for ED, free testosterone levels were associated positively with peak systolic velocity and resistive index and negatively associated with end-diastolic velocity.68 Although the significance is as yet unknown, there may be a locally mediated acute effect of testosterone because levels vary at the time of erection within serum and the corpora cavernosa.69,70
The correlation between low testosterone and decreased erectile function has been studied in animal models to elucidate the physiologic mechanism. In rats castrated for 2 weeks, a prolonged latency period and decreased filling rate of the cavernosa, as well as decreased intracavernosal pressure, were observed.71 Overall, a 50% decrease in erectile response was noted, which was restored with testosterone or dihydrotestosterone (DHT) supplementation.71,72 Dai and colleagues73 demonstrated reduced veno-occlusion in electrically induced erections in castrated rats, which was restored with testosterone supplementation. This effect appeared to be mediated by NO.73 Studies have demonstrated that testosterone and DHT stimulate nNOS gene expression and increase NO in the corpora during erections.72,74 Van den Broeck and colleagues75 confirmed dose-dependent relaxation of human corpora cavernosal tissue with increasing testosterone and DHT.
*Hyperprolactinemia
Hyperprolactinemia results in reproductive as well as sexual dysfunction. Symptoms associated with hyperprolactinemia include loss of libido, ED, galactorrhea, gynecomastia, and infertility. These symptoms typically occur only at severely elevated levels (>35 ng/mL or 735 mU/L).76 Hyperprolactinemia may be idiopathic, drug-induced, secondary to a pituitary adenoma, or related to chronic renal failure.77 Concomitant low testosterone most likely is mediated by prolactin-induced inhibition of gonadotropin-releasing hormone secretion by the pituitary gland.77
*Thyroid dysfunction
Hyperthyroidism or hypothyroidism also may be associated with ED. In a small study of patients with hyperthyroidism and hypothyroidism (71 total patients), 70% and 84% of patients reported at least mild ED, with a Sexual Health Inventory for Men (SHIM) score of less than 21, respectively, compared with 34% of the control group.78 With treatment, statistically significant mean increases in SHIM scores of 7 points in the hyperthyroidism cohort and 8.5 points in the hypothyroidism cohort were noted. 78 Thyroid hormone effects may be mediated by secondary effects on other hormones known to be associated with sexual function. Hypothyroidism is associated with increased serum prolactin and decreased serum testosterone whereas hyperthyroidism is associated with increased estrogen levels.79–81 A direct effect of thyroxine may also be at play in thyroid hormone ED because both alpha and beta thyroxine receptors have been shown to be present in endothelial and smooth muscle cells from human corpora cavernosa.82 Impairment in NO-dependent relaxation of the corpora cavernosa has been reported in animal models of hyperthyroidism.83,84
Psychogenic
Historically, psychogenic issues were thought to be the principal etiology for the vast majority of ED presentations. Pscyhogenic ED may not be a primary etiology in most cases but it is a contributing factor in virtually all cases. There are conflicting data as to whether purely psychogenic ED may be more common among younger patients (<40 years old), with the reported incidence varying from 13% to 83%.85–87 The degree to which ED is psychogenic versus physiologic is difficult to parse out; isolated psychogenic ED is considered a diagnosis of exclusion clinically.
SUMMARY
Advances in neuroimaging and understanding molecular physiology have clarified the biological processes underlying penile erection. This information contributes to the understanding of the scientific basis of ED. Comorbidities that predispose to ED cause concomitant physiologic changes within multiple categories of ED (ie, vasculogenic, neurogenic, endocrine, and psychogenic). An array of disruptions at the molecular (cell signaling and responsiveness to neurotransmitters) and structural (changes in the tunica albuginea, smooth muscle, or vasculature) levels may contribute to ED. Evolving understanding of the science of erections and the pathophysiology of ED helps clinicians guide current and future therapy for patients.
