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Beyond hypertension, ED may also predict the presence of occult coronary disease. One study evaluated 50 men with ED and no clinical signs of cardiovascular disease. The men were age 40–60 years and underwent cardiac stress testing and coronary angiography.

Eighty percent of the men demonstrated significant cardiovascular risk factors. Stress testing showed myocardial ischemia in 56% of these men. Coronary angiography was performed in 20 of the men with ischemia. Angiography revealed left main stem or severe three-vessel disease in 6 of 20, with some degree of significant coronary artery disease (CAD) in 40% of the total. It is important to note that none of these 50 men showed any clinical signs of ischemic heart disease prior to this testing that was prompted only by the presence of ED.

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Thompson et al. reported a secondary finding in a randomized study of almost 10,000 men age 55 or older enrolled in the Prostate Cancer Prevention Trial.

The secondary finding was a direct association between ED and subsequent cardiovascular disease. Eighty-five percent of the men had no cardiovascular disease at the start of the study, with 47% of these men having ED at that time. Incident ED that occurred during the first 5 years of the study was associated with a 1.25 increased risk of subsequent cardiac event during follow-up. In reference to subsequent cardiovascular events, the risk was 0.015 per personyear among those without ED at study entry, and was 0.024 per person-year for those with preexisting ED at the time of study entry. These authors stated that this increased associated risk was similar to the risk associated with smoking or a family history of myocardial infarction, thus clearly echoing the concept that ED should prompt cardiac investigation in these patients.

A smaller investigation using 285 patients looked at the specific extent of CAD in relation to ED. They divided patients into age-matched groups based on acute single vessel disease, acute two or three vessel disease, or chronic coronary syndrome. A control group included those with normal angiography but with suspected CAD. They found that both multiple vessel disease and chronic coronary syndrome were independent predictors of ED. They also found that, in patients with established CAD, clinical presentation of ED comes before CAD in the majority of these patients by an average of 2–3 years.

Although ED has been found to affect about 75% of patients with chronic CAD, the topic is not generally an accepted part of cardiologists’ patient evaluation. Reportedly 25% of these patients experience severe ED. The same study also delved into specific cardiac disease states and their association with various degrees of ED. They found that ED had a prevalence of about 60% in men with a history of prior myocardial infarction or coronary artery bypass surgery.

These authors echoed the assumption that these outcomes were related to endothelial dysfunction and atherosclerosis. They also theorized that the endothelial damage that occurred as a result of smoking, hypertension, lipid disorders, and diabetes diffusely affected vasculature of the body, including the arterial blood supply to the corpora cavernosa of the penis. They warned that ED may be the warning sign for undiagnosed CAD.

Hypertension Erectile dysfunction has a high prevalence among patients with both treated and untreated hypertension. Large studies have confirmed that, not only was ED more prevalent in patients with elevated blood pressure than controls, but also that the degree of ED that experienced by patients with hypertension was also more severe in nature than in the general population.

One study highlighted the specific penile vascular effects of hypertension through the use of rat models.
The study found that hypertensive rats demonstrate impairment in endothelial-mediated relaxation of corporal cavernosal strips in response to acetylcholine. This finding suggested that a defect exists in endothelial-dependent reactivity as well as a reduction in nitric oxide in the presence of hypertension.

It is somewhat more difficult to evaluate the exact effect of hypertension on erectile function in humans. Patients are often being treated for their hypertension with medications that are themselves known to cause ED, such as beta blockers and thiazides. It is likely that the ED experienced in hypertensive men is caused by penile vascular arterial changes including atherosclerosis Obesity Obesity, which is an independent risk factor for cardiovascular disease, is also associated with ED. Esposito et al. showed that intervention with the modification of lifestyle behaviors that led to weight loss and decreased cardiac risk also led to the improvement in erectile function.

A decrease in body mass index may reduce the risk of both ED and endothelial dysfunction in obese men.
If obesity is positively associated with endothelial dysfunction and increased serum concentrations of vascular inflammatory makers, with what has been previously aforementioned, it would appear that a common pathway exists – patients suffer from both increased cardiovascular risk and ED per similar physiologic pathways.

In a more recent publication, Esposito et al. stated that obesity increases ED risk by 30–90% compared to controls. The authors again agreed that lifestyle changes aimed at reducing body mass index improves both erectile and endothelial function in men. In addition, they mentioned that Mediterranean-style diet may aid sexual function.

A separate literature review in 2006 was completely dedicated to the topic of the Mediterranean-style diet and its relation to sexual function. They found that sexual function can improve in as little as 2 years through exercise and adoption of the Mediterranean-style diet. Specifically, men consuming more fruits, vegetables, nuts, whole grain, and olive oil as compared with controls were found to have an improved endothelial function score and improved levels of inflammatory markers.

Atherosclerosis The most common recognized cause of ED is atherosclerosis. Atherosclerosis is known to be associated with such cardiovascular diagnoses as hypertension and dyslipidemia, which produce oxidative stress and damage to the endothelial cells.

The underlying pathophysiology seems to stem from endothelial cell dysfunction, which would be a common factor between general cardiovascular disease and ED. Failed vasodilation seen in ED is a direct effect of the inability of smooth muscle cells lining the arterioles to relax. Atherosclerosis has been found to be associated with up to 40% of cases of ED in men over age 50.

Cholesterol One group looked at cavernous biopsies of rabbits after three months of a cholesterol-rich diet versus controls. The control group showed normal muscle cells on biopsy while the high cholesterol group showed muscle cell degeneration. This tangible evidence of direct effect of high cholesterol diet on cavernous muscle cells suggests that abnormalities in lipid metabolism has a direct effect on cavernous smooth muscle cell degeneration, thus contributing to ED.

Hypercholesterolemia is a known direct risk factor for cardiovascular disease. Erectile dysfunction in association with hypercholesterolemia was documented in a group of healthy men with no known cardiac risk factors.

These otherwise healthy men with ED were found to have abnormal cholesterol levels at a rate of 60%. In addition, over 90% of these men with abnormal cholesterol levels were also noted to have penile arterial disease on Doppler ultrasound.

Saltzman et al. evaluated men with ED in which their only known risk factor was hypercholesterolemia. They were able to meet their treatment goals of total cholesterol less than 200 mg/dl and LDL less than 120 mg/dl. They found that ED improved in men with hypercholesterolemia when treated with a statin drug.

The resulting decreased cholesterol levels improved ED while also decreasing overall cardiovascular risk. Primary care physicians may theoretically have more success with patient compliance of statin drugs for current improved sexual function than for future cardiovascular risk. Of note, there is also contradicting evidence, based on literature review, that statins and fibrates may actually cause or worsen ED.

Should this be the case, it would be very difficult to determine the effect of cholesterol on ED, as in order to treat a known risk factor of ED, we may be in effect worsening ED with the use of medication.

Over the past decade, there has been an increased interest and focus of urologic research on the field of ED. Particular focus has been on ED and its correlation with cardiovascular disease. Many disease states already known to be associated with ED are also associated with cardiovascular disease. These disease states include hypertension, atherosclerosis, diabetes, peripheral vascular disease, obesity, sedentary lifestyle, and myocardial infarction.

The latest research has been aimed at verifying a direct correlation between ED and cardiovascular disease. There has even been suggestion that ED is often the first clinical manifestation of underlying cardiovascular disease in up to 30% of men presenting with erectile dysfunction. If so, it would be increasingly important for men to disclose symptoms of ED to their primary care providers, as ED might represent an opportunity to evaluate these men for cardiovascular disease. Unfortunately, a reported 90% of men with ED do not discuss this information with their primary provider.

It can be speculated that the reason for underreporting ED is due to patients’ embarrassment in addressing sexual issues with a healthcare provider. Other possibilities are that patients believe the issue resolves without intervention, or that ED is just a normal symptom of aging. Doctors caring for these patients may then be missing the opportunity to prevent cardiovascular morbidity and mortality.

The MMAS of the early 1990s opened the door to increased awareness of the correlation between ED and cardiovascular disease.

This study was the first large scale, population-based study investigating ED, revealing that increased prevalence of ED correlated directly with increasing age. The study evaluated 1,290 randomly selected men and found a clinically significant correlation between ED and other medical comorbidities independent of age. These comorbidities included hypertension, hypercholesterolemia, diabetes, and cardiovascular disease. Patients treated for hypertension had a 15% likelihood of also having complete ED and those with cardiac disease had a 39% likelihood of ED.

Schouten recently conducted a longitudinal, population-based study focused specifically on erectile rigidity as an independent indicator for upcoming cardiovascular events. They found that severely reduced erectile rigidity had a hazardratio of 3.8 for the presentation of cardiovascular disease within 6 years. They agreed that a single question focused on the presence of ED should be incorporated into cardiovascular risk assessment in men. They also stated that men presenting only with the complaint of ED should be evaluated for cardiovascular risk

Risk factors for ED have been delineated in large prospective studies, such as Massachusetts Male Aging Study (MMAS), Boston Area Community Health Survey (BACHS), and Health Professionals Follow-up Study (HPFS). The MMAS study reported on males between ages 40 and 70 years and found that erectile function declined precipitously with age. Overall, the study found that 52% of men within this age range suffered from some degree of ED. Diabetes, heart disease, and hypertension increased the risk of ED significantly in this study.

Erectile dysfunction was studied in men aged 45–70 years with a 14-year follow-up in the HPFS. Excluding men who developed prostate cancer, the relative risk (RR) of development of ED as per self-assessment was 1.5 for current smokers and 1.9 for obese men. In contrast, moderate exercise decreased the risk of ED. Interestingly, these risk factors produced greater effect in men 55 years or younger.

The BACHS was created specifically to assess urologic symptoms in a diverse cohort.

• This study found a dose-response effect of tobacco cigarettes on ED, although there was not a significant increase in the odds of developing ED until over 20 pack-years of the habit.
• They also found that low socioeconomic status, independent of other risk factors, including race, was a risk factor for ED.

Erectile Physiology A successful male penile erection requires two processes. Cavernosal artery smooth muscle relaxation and increased venous outflow resistance. In order to sustain an erection one must achieve and maintain a high arterial inflow and a low venous outflow. Cavernosal arterial smooth muscle relaxation is an active process and the initial event of an erection. viagra tablets online

1. Smooth muscle relaxation leads to arterial dilation which results in increased penile blood flow that in turn causes radial and longitudinal cavernosal expansion. This process is mediated by nitric oxide released through stimulation of nonadrenergic, noncholinergic nerves (NANC).

2. Nitric oxide binds to smooth muscle cells stimulating the production of cyclic GMP, which then decreases intracellular calcium and causes relaxation. Cyclic AMP, a second minor messenger, acts in a similar manner to decrease intracellular calcium and causes muscle relaxation.

Venous outflow resistance, in contrast to arterial smooth muscle relaxation, is a passive process. As the cavernosal tissues engorge and expand, they compress the subtunical venous sinuses and cause the outflow resistance necessary to maintain an erection.

Understanding the psychological aspects of ED requires understanding the connection between the brain and the penis. There are two basic inputs leading to sexual arousal and, therefore, erections. One is physiological and results from direct stimulation of the penis. This reflexogenic input is centered in the sacral regions of the spinal cord and is primarily under parasympathetic nervous system control.

The other is psychological and results from mental experiences in the brain which are transmitted to the penis. This psychogenic input is mediated in the cerebral cortex. The brain is the source of both excitatory and inhibitory influences on erections. The inhibitory pathway is under serotonergic control, while the excitatory pathway is under the influence of the neurotransmitter oxytocin. The medial parietooccipital region of the limbic system has a primarily inhibitory role, such as in the fight-or-flight response. The sexual centers of the brain, particularly the midbrain, hypothalamus, and amygdala respond to gonadal hormones and, thus, are part of the hormonal feedback system that shapes sexual behavior. The reticular activating system has an important triage role through its connections between higher and lower brain structures as they process sexual stimuli.

These connect to one of two coordinating nerve centers along the spinal cord. More simply stated, erections are the result of friction and fantasy. An implication of these two inputs to erectile response is that mental experiences, i.e., thoughts, feelings, memories, and fantasies, have a central role in normal sexual response and are crucial factors in the development of sexual dysfunctions.

Bancroft and Janssen have proposed a dual control model of erectile function that includes both excitatory and inhibitory influences on sexual response, which is similar to the model of CNS control over erections described above. This model emphasizes that higher brain functions (e.g., thoughts and feelings) can impact erectile response positively or negatively. For example, a common manifestation of ED is the man who, while experiencing sexual arousal, becomes anxious about his performance and loses his erection.

The inhibitory influence of sympathetic nervous system arousal on erectile response is the biological basis to many of the psychological origins of ED.

Everhard and colleagues have posited a complex feedback process for sexual arousal that incorporates physiological response, the immediate situation or context, emotional arousal, and cognitive appraisal. This understanding of the neurological control involved in sexual response highlights the interdependence of psychological and physiological aspects of ED.

Because the brain is intimately involved in the control of erections, a wide variety of psychological factors impact erectile response and may lead to erectile dysfunction (ED).

This chapter reviews the assessment of psychological factors in ED, the immediate and underlying psychological conditions involved, and the development of ED over time. Outcome research on psychological treatments for ED is also reviewed. The goal of the chapter is to help health care providers to conduct a comprehensive evaluation of ED that is sensitive to psychological factors.

A comprehensive understanding of erectile dysfunction (ED) must incorporate both the physical and the psychological aspects of erectile response. An erection is best characterized as a psychophysiological phenomenon that depends on a complex interplay of biological and psychological factors. Impairment in any of these aspects may lead to erectile dysfunction. The focus of this chapter is on the assessment of psychological factors that contribute to erection difficulties. The evidence regarding the outcome of psychological treatments and the integration of medical and psychological treatments are also reviewed.

The definition of psychological factors to be used here encompasses a variety of mental aspects of sexuality.

1. First are the behavioral aspects, which primarily involve who does what to whom in the sexual encounter.
2. Second are the emotional aspects of the sexual response, that is, feelings during sex, as well as the emotional needs associated with sex.
3. Third are the cognitive aspects of sexual response, which include knowledge, beliefs, and attitudes about sexuality.
4. Fourth are the interpersonal aspects, i.e., the couple’s interaction and the quality of the relationship, both sexual and emotional.
5. Fifth are the cultural aspects of sexuality, which entail the expectations and norms that shape sexual behavior.

It is also important to note that, while most of these aspects of sexuality are either observable or may be described by the patient, much of what is referred to as psychological is either unconscious or inaccessible to the individual himself.

Nitric Oxide NO is emerging as an essential neurotransmitter within the CNS for erectile response. NO appears to act in several regions of the brain, including the MPOA and PVN.

Injection of NO-synthase (NOS) inhibitors into the PVN prevents penile erection induced by dopamine agonists and oxytocin.

NO production increased in the PVN of rats during noncontact erections, confirming the role of NO production during erection.

ACTH and a-MSH Adrenocorticotropic hormone (ACTH) and its related peptide a(alpha)-melanocyte stimulating hormone (a-MSH) have been shown to elicit erectile responses in addition to increased grooming, stretching, and yawning behaviors when given intracerebroventricularly to lab animals.

This proerectile effect appears to be due to the stimulation of melanocortin-3 (MC3) receptors which are prevalent in the hypothalamus and limbic system. The role of these peptides in erectile response is not entirely known, but they appear to induce erection by acting at sites distinct from those in the PVN stimulated by dopamine and oxytocin.  Additionally, Melanotan II, an a-MSH synthetic analog, has had proerectile effects in humans with psychogenic impotence.

Other Neurotransmitters Excitatory amino acids, such as l-glutamate, N-methyl-d-aspartate (NMDA), amino-3-hydroxy- 5-methyl-isoxazole-4-propionic acid (AMPA), and trans-1-amino-1,3-cyclo-pentadicarboxylic acid (ACPD) have been shown to have proerectile effects when injected into the MPOA or PVN of lab animals. Gamma-amino butyric acid (GABA) appears to function as an inhibitor in the reflex pathways for penile erection. Stimulation of opiod m receptors appears to centrally prevent penile erection and impair copulation likely through the prevention of the increased NO production in the PVN during sexual activity.

Oxytocin Proerectile projections from the supraoptic area of the hypothalamus and the PVN travel to the spinal centers for erection and oxytocin has been shown to be a key neurotransmitter in these neurons. In lab animals, intracerebroventricular or intrathecal injection of oxytocin antagonists blocks the induction of erection that is seen with intrathecal oxytocin injection. Additionally, antagonist injection into the lateral ventricles leads to a dose dependant reduction in noncontact erections.

This has led to the belief that oxytocin plays a role in facilitating nonreflexive erections. Dopamine Dopaminergic neurons project to the MPOA and PVN  and also have been discovered to travel from the caudal hypothalamus to the lumbosacral spinal cord.

Dopamine is thought to participate in central regulation of the autonomic and somatic penile reflexes. The dopamine receptor agonist, apomorphine, induces penile erection in rats when administered systemically. Additionally, apomorphine injection into the MPOA facilitated erections while dopaminergic antagonist injection into the MPOA decreased penile reflexes.

In the PVN, dopaminergic neurons appear to stimulate oxytocinergic neurons, which then more directly account for the erectile response. This is supported by the prevention of apomorphine-induced erections in the presence of oxytocin receptor antagonists.

Serotonin In experimental animal models, bulbospinal neurons containing serotonin (5-HT) project to the lumbar spinal cord. Serotonergic fibers have been demonstrated in close proximity to retrogradely labeled sacral preganglionic neurons.

One study showed 5-HT in general had an inhibitory effect on male sexual behavior. However, there have been conflicting reports with another study showing that the stimulation of 5-HT2c receptors mediated the erectile response. Thus, the full function of 5-HT in erectile function has not been fully elucidated. It appears to serve various functions likely acting as a major modulator of the central control of erection.

Paraventricular Nucleus The hypothalamic paraventricular nucleus (PVN) contains premotor neurons that project from the parvocellular layer directly into the spinal cord.

These neurons have been shown to contain a variety of neurotransmitters: oxytocin, vasopressin, enkephalins, and dopamine. In rat models injection of a variety of neuromediators (oxytocin, glutamate, nitric oxide, dopamine agonists) into the PVN has been shown to elicit penile erection.

Additionally, in both rats and monkeys, stimulation of the PVN elicits erection. Lesion of the parvocellular layer of the PVN causes longer latencies and fewer noncontact erections in rats. Parvocellular PVN neurons have been shown to respond to stimulation of the dorsal nerve of the penis in rats, suggesting that the PVN may be a supraspinal reflex center for erections.viagra professional Canada

The PVN also receives input from the medial preoptic area (MPOA) suggesting that the PVN serves to integrate MPOA input before sending it downstream via autonomic pathways selectively activated within the PVN Medial Preoptic Area The MPOA of the hypothalamus is key to sexual behavior.

In rats and monkeys, MPOA stimulation elicits erection. In monkeys, increases in MPOA neuronal activity have been recorded during erection. Interestingly, MPOA lesions do not affect reflexive or noncontact erections.

All of this has led to debate as to the role of the MPOA in erectile function. The emerging theory is that the MPOA likely serves as an integration center of hormonal and sensory inputs for sexual behavior and redistributes these signals to the hypothalamic and brainstem structures thought to be more directly linked to erectile control, such as the PVN.

Other Supraspinal Centers Many other supraspinal areas have been shown in animal studies to be related to erectile function. In monkeys, isolated stimulation of the medial dorsal nucleus of the thalamus, ventral tegmental area, precallosal cingulate gyrus, and subcallosal and caudal gyrus led to erections.

Hippocampal stimulation in anesthetized rats increased intracavernous pressures as did desynchronization of the somatosensory cortex following cocaine administration. A center for descending the inhibition of spinal sexual reflexes has been localized to a group of neurons in the paragigantocellular reticular nucleus of the ventral medulla.

The exact role each supraspinal area plays in mediating erection is currently unclear. However, it is apparent that there are extensive interconnections between many supraspinal centers that contribute to descending pathways and exert powerful control, both inhibitory and excitatory, on the spinal responses driving erection.