Materiały źródłowe

• #1 Erectile Dysfunction – StatPearls – NCBI BookshelfTwitterFacebookLinkedInGitHubNCBI Insights BlogTwitterFacebookYoutube

  https://www.ncbi.nlm.nih.gov/books/NBK562253/

  Erectile dysfunction (ED) is a prevalent and multifaceted condition that predominantly afflicts males beyond 40 years, with its prevalence escalating globally. This condition is characterized by the consistent or recurrent inability to attain and maintain an erection sufficient for satisfactory sexual performance. The etiology of ED is diverse, encompassing organic, psychogenic, and mixed factors, often interwoven with comorbidities such as diabetes, cardiovascular disease, and neurologic disorders. This complexity underscores the significance of discerning the root causes to guide appropriate management. […] ED can be a symptom of a wide range of underlying pathologies and is an essential but underutilized cardiovascular risk factor. Any disease process that affects penile arteries, nerves, hormone levels, smooth muscle tissue, corporal endothelium, or tunica albuginea can cause erectile dysfunction. This condition is closely related to cardiovascular disease, diabetes mellitus, hyperlipidemia, and hypertension, among other disorders. Endothelial dysfunction appears to be the other common pathway in patients with this condition.

• #1 Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1351051/

  The molecular and clinical understanding of erectile function continues to gain ground at a particularly fast rate. Advances in gene discovery have aided greatly in working knowledge of smooth muscle relaxation/contraction pathways. […] The understanding of the nitric oxide pathway has aided not only in the molecular understanding of the tumescence but also aided greatly in the therapy of erectile dysfunction. […] Erection thus involves sinusoidal relaxation, arterial dilatation, and venous compression. The importance of smooth muscle relaxation has been demonstrated in animal and human studies. […] Sexual behavior and penile erection are controlled by the hypothalamus, the limbic system, and the cerebral cortex. Therefore, stimulatory or inhibitory messages can be relayed to the spinal erection centers to facilitate or inhibit erection.

• #1 Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction | Abdominal Key

  https://abdominalkey.com/physiology-of-penile-erection-and-pathophysiology-of-erectile-dysfunction/

  Erection thus involves sinusoidal relaxation, arterial dilation, and venous compression. […] The current consensus holds that the maintenance of the intracorporeal smooth muscle in a semicontracted (flaccid) state likely results from three factors: intrinsic myogenic activity; adrenergic neurotransmission; and endothelium-derived contracting factors such as angiotensin II, PGF2, and endothelins. On the other hand, detumescence after erection may be a result of cessation of NO release, the breakdown of cyclic guanosine monophosphate (cGMP) by phosphodiesterases, and/or sympathetic discharge during ejaculation. […] Most researchers now agree that NO released from nonadrenergic/noncholinergic (NANC) neurotransmission and from the endothelium is the principal neurotransmitter mediating penile erection. NO increases the production of cGMP, which in turn relaxes the cavernous smooth muscle.

• #1 Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction | Abdominal Key

  https://abdominalkey.com/physiology-of-penile-erection-and-pathophysiology-of-erectile-dysfunction/

  The penile erectile tissue, specifically the cavernous smooth musculature and the smooth muscles of the arteriolar and arterial walls, plays a key role in the erectile process. In the flaccid state, these smooth muscles are tonically contracted, allowing only a small amount of arterial flow for nutritional purposes. […] Sexual stimulation triggers release of neurotransmitters from the cavernous nerve terminals. This results in relaxation of these smooth muscles and the following events: (1) dilation of the arterioles and arteries by increased blood flow in both the diastolic and systolic phases; (2) trapping of the incoming blood by the expanding sinusoids; (3) compression of the subtunical venous plexuses between the tunica albuginea and the peripheral sinusoids, reducing venous outflow; (4) stretching of the tunica to its capacity, which occludes the emissary veins between the inner circular and outer longitudinal layers and further decreases venous outflow to a minimum; (5) an increase in P O2 (to about 90 mm Hg) and intracavernous pressure (around 100 mm Hg), which raises the penis from the dependent position to the erect state (the full-erection phase); and (6) a further pressure increase (to several hundred millimeters of mercury) with contraction of the ischiocavernosus muscles (rigid-erection phase).

• #1 Erectile Dysfunction – StatPearls – NCBI BookshelfTwitterFacebookLinkedInGitHubNCBI Insights BlogTwitterFacebookYoutube

  https://www.ncbi.nlm.nih.gov/books/NBK562253/

  While the vast majority of patients with ED will have organic disease, some may have a primary psychological issue, particularly younger men. Even when the underlying cause is organic, there are almost always psychological consequences to ED regarding marital and relationship issues, cultural norms and expectations, loss of self-esteem, shame, anxiety, and depression, among others. ED can cause considerable emotional damage to the patient and their partner, as well as have a significant impact on their quality of life. Fortunately, ED is almost always treatable. […] The cause of ED is often multifactorial. Distinguish whether the condition has an underlying psychological cause or an organic etiology. Depression, performance anxiety, and other sexual disorders can be strong contributing factors even when organic causes also exist. Aging is an essential factor contributing to ED. As patients age, cardiovascular diseases, hypertension, and other co-morbidities play an increasingly significant role in this condition. Diabetes mellitus and metabolic syndrome can affect several organ systems, resulting in the accelerated deterioration of erectile function, and can disrupt the mechanisms underpinning erections on a molecular level.

• #1

  https://journals.lww.com/ijoru/fulltext/2024/02010/etiology,_surgical_anatomy,_and_pathophysiology_of.2.aspx

  Organic ED can further be subdivided into vasculogenic (arteriogenic, cavernosal, and mixed), neurogenic, endocrinologic, anatomic, and drug-induced ED. […] There is a strong correlation between CVD and ED, and often ED can be the first sign of CVD. […] Therefore, any pathology interfering with NO signaling will compromise erectile function, as vascular disease is highly correlated with impaired NO signaling. […] The pathophysiology of ED can be categorized into psychogenic and organic. Psychogenic ED can either be generalized, often secondary to age-related libido decrease, or situational (partner or performance-related). […] Many classifications of ED have been published. […] The most common medications that have proven to induce ED include diuretics, alpha-blockers, antipsychotics, antiandrogens, statins, and recreational drugs, such as anabolic steroids, cocaine, and alcohol. […] Despite major advances in the knowledge of ED etiology and physiopathology, there remain areas to be addressed to improve the current state of knowledge.

• #1 Erectile Dysfunction – StatPearls – NCBI BookshelfTwitterFacebookLinkedInGitHubNCBI Insights BlogTwitterFacebookYoutube

  https://www.ncbi.nlm.nih.gov/books/NBK562253/

  Cardiovascular disease is a very significant risk factor for ED. Almost 50% of men with known coronary artery disease proven by cardiac catheterization have significant ED. Part of the reason for this is that the coronary arteries and the penile cavernosal arteries are similar in size and tend to develop atherosclerotic problems similarly. Since the cavernosal arteries are small, they can develop blockages from atherosclerotic plaques earlier, resulting in vasculogenic ED years before the clinical appearance of coronary artery disease. Both cardiovascular disease and ED involve endothelial cell dysfunction in their pathophysiology. […] Patients will often demonstrate subclinical atherosclerosis long before any overt ED by as much as 10 years. The cavernosal arteries being of smaller diameter means that vasculogenic ED often precedes coronary artery disease, myocardial infarctions, and strokes by up to 5 years.

• #1 Pathophysiology of erectile dysfunction: the contributions of trabecular structure to function and the role of functional antagonism | International Journal of Impotence Research

  https://www.nature.com/articles/3900576

  Erectile dysfunction (ED) is estimated to impact more than 150 million men this year worldwide. […] An understanding of the pathophysiology of ED both furthers the basic scientific knowledge of disease processes and provides a rational design of pharmacotherapy. […] At present, there are two major views regarding the pathophysiology of ED. In the first hypothesis, the oxygen tension-dependent changes in the penis during erection are proposed to impact corpus cavernosum structure by inducing various cytokines, vasoactive factors and growth factors at the two different oxygen tensions (flaccidity and erection) which, in turn, alter smooth muscle metabolism and connective tissue synthesis. […] Decreases in the corpus cavernosum smooth muscle/connective tissue ratio have been correlated with an increased likelihood of diffuse venous leak and a failure of the veno-occlusive mechanism in prospective patient studies.

• #1 Erectile Dysfunction: From Pathophysiology to Clinical Assessment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-11701-5_3

  The functional change resulting from such injuries is the reduction in NO load that is available to the smooth muscle. The structural changes center on apoptosis of the smooth muscle and endothelial cells of the blood vessels, as well as upregulation of fibrogenetic cytokines that lead to collagenization of the smooth muscle. These changes result in veno-occlusive dysfunction (venous leak). Vascular disease and endothelial dysfunction lead to erectile dysfunction through reduced blood inflow, arterial insufficiency, or arterial stenosis. […] Many men assume that erectile dysfunction is a natural consequence of aging. But, despite age stands as an independent risk factor for ED, about one-third of 70-year-old men report no erectile difficulties. […] Risk factors for developing erectile dysfunction include tobacco use, obesity, sedentary lifestyle, and chronic alcohol use.

• #1 Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1351051/

  It has been estimated that 10 to 19% of ED is of neurogenic origin. […] The MPOA, the paraventricular nucleus, and the hippocampus have been regarded as important integration centers for sexual drive and penile erection. […] In men with a spinal cord injury, their erectile function depends largely on the nature, location, and extent of the spinal lesion. […] Atherosclerotic or traumatic arterial occlusive disease of the hypogastric-cavernous-helicine arterial tree can decrease the perfusion pressure and arterial flow to the sinusoidal spaces, thus increasing the time to maximal erection and decreasing the rigidity of the erect penis. […] Failure of adequate venous occlusion has been proposed as one of the most common causes of vasculogenic impotence. […] By release of vasoactive agents, the endothelium of the corpus cavernosum can modify the tone of adjacent smooth muscle and affect the development or inhibition of an erection.

• #1 Erectile dysfunction – symptoms and treatment | healthdirect

  https://www.healthdirect.gov.au/erectile-dysfunction

  Erectile dysfunction (also known as ED or impotence) is when you can’t get or keep an erection, leading to problems with sexual intercourse. […] Erectile dysfunction can have a range of causes, both physical and psychological. […] Erectile dysfunction can have a range of causes physical, psychological or a combination. Sometimes it only happens in certain situations. The cause may not always be clear. […] Problems with the male reproductive system that can cause erectile dysfunction include: Peyronie’s disease (scar tissue inside the penis that results in a curved penis), prostate disease, and treatments for prostate cancer or an enlarged prostate, hypogonadism, where the testicles cannot make enough testosterone. […] Physical factors that can cause erectile dysfunction include: health problems that affect the nerves, like spinal cord injury, Parkinson’s disease and Alzheimer’s disease, reduced blood flow to the penis, caused by atherosclerosis (clogging of the arteries), hormonal problems, including underactive thyroid (hypothyroidism), growth hormone conditions and having too much cortisol, alcohol, smoking or substance abuse, some medicines used to treat high blood pressure, high cholesterol, depression or prostate cancer.

• #1

  https://journals.lww.com/jodb/fulltext/2020/11010/erectile_dysfunction_in_diabetes_mellitus__a.1.aspx

  Rho A/Rho-Kinase pathway is the key pathway which inhibits relaxation of the penile smooth muscle vasculature. […] Diabetic neuropathy is the most common diabetic complication, affecting 10%90% of people with diabetes, depending on the diagnostic criteria and the age and duration of DM. Some studies showed an earlier development of DN in men, compared to women. Neuropathy is a very important pathogenetic factor in the development of ED.

• #1 The Connection Between Prostate Cancer and Erectile Dysfunction | Department of Surgery | Washington University in St. Louis

  https://surgery.wustl.edu/the-connection-between-prostate-cancer-and-erectile-dysfunction/

  Prostate cancer does not directly cause ED, but treatments for prostate cancer can cause a patient to experience this condition. […] In fact, ED is one of the most common side effects after any kind of prostate cancer treatment. […] Treatments for prostate cancer can decrease your body’s ability to create testosterone. […] Low testosterone can impact your libido and ability to achieve and maintain an erection. […] Other treatments, such as prostatectomy, can affect the blood vessels and nerves responsible for causing erections. […] If these structures in your body experience trauma, it can make it more difficult for them to work properly, causing ED. […] Prostatectomy, or surgery to remove the prostate, can also affect your ability to produce ejaculate. […] Identifying the organic cause and prostate cancer treatment can help relieve the symptom of ED. […] Treatments for prostate cancer that may also indirectly improve ED include surgery, radiation therapy, systemic therapy and focal therapy.

• #1 Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments

  https://www.mdpi.com/1467-3045/46/8/521

  Oxidative stress is linked to both vasculogenic as well as neurogenic ED, with the former being more extensively studied. Superoxides produced by vascular sources within the penis react with NO to create RNS like peroxynitrite, which causes oxidative DNA damage and disrupts lipids and proteins. This contributes to endothelial dysfunction by impairing NO availability. […] ROS produced in smooth muscle and endothelial cells can scavenge NO, influencing the expression and activity of eNOS. ROS also deplete cofactors necessary for NOS function, generate vasoconstrictors, reduce smooth muscle cell integrity, deactivate antioxidants, and cause structural and functional alterations in blood vessels. Elevated oxidative stress can contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), the primary cholesterol transporter in the blood, and increasing superoxide production. […] ROS impact the transmission of nitrergic neurotransmitters by causing the death of nitrergic neurons and reducing the signaling of nNOS, leading to ED.

• #1 Erectile Dysfunction: From Pathophysiology to Clinical Assessment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-11701-5_3

  Several studies have suggested that chronic inflammation and circulating inflammatory markers affect systemic endothelial function. […] Androgens play an important role in both penile and vascular health, with cellular targets located in both endothelial and smooth muscle cells. […] Within the penis, low androgen levels are associated with apoptosis of endothelial and smooth muscle cells as well as with pathologic structural remodeling. […] The metabolic syndrome also known as syndrome X and insulin resistance syndrome is the term that consists of a cluster of disease states abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance glucose intolerance, proinflammatory state, and prothrombotic state. […] Coronary artery diseases and ED share similar risk factors such as hypertension, diabetes mellitus, smoking, and hypercholesterolemia, and many of these factors are part of MetS.

• #1

  https://www.baus.org.uk/patients/conditions/3/erectile_dysfunction_impotence/

  Erectile dysfunction (impotence) is defined as an inability to obtain or maintain an erection sufficient for penetration and for the satisfaction of both sexual partners. […] Erectile dysfunction can be caused by many factors and may have a gradual or sudden onset. […] Erectile dysfunction can also be a sign of other illnesses such as heart disease or diabetes, so it is important that you seek medical advice. […] 90% of men with impotence (erectile dysfunction) have at least one underlying physical cause for their problem. […] A psychological component, often called „performance anxiety”, is common in men with impotence. However, a purely psychological problem is seen in only 10%. […] Of the 90% of men who have an underlying physical cause, the main abnormalities found are: Cardiovascular disease in 40%; Diabetes in 33%; Hormone problems (e.g. high prolactin or low testosterone levels) in 11%; Neurological disorders in 10%; Pelvic surgery or trauma in 3-5%; and Anatomical abnormalities in 1-3%.

• #1 Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments

  https://www.mdpi.com/1467-3045/46/8/521

  Erectile dysfunction (ED) is a prevalent condition affecting men’s sexual health, with oxidative stress (OS) having recently been identified as a significant contributing causative factor. This narrative review aims to elucidate the role of OS in the pathophysiology of ED, focusing on impact, mechanisms, and potential therapeutic interventions. Key findings indicate that OS disrupts endothelial function and nitric oxide (NO) signaling, crucial for erectile function. Various sources of reactive oxygen species (ROS) and their detrimental effects on penile tissue are discussed, including aging, diabetes mellitus, hypertension, hyperlipidemia, smoking, obesity, alcohol consumption, psychological stress, hyperhomocysteinemia, chronic kidney disease, and sickle cell disease. Major sources of ROS, such as NADPH oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), and mitochondrial electron transport, are identified. NO is scavenged by these ROS, leading to endothelial dysfunction characterized by reduced NO availability, impaired vasodilation, increased vascular tone, and inflammation. This ultimately results in ED due to decreased blood flow to penile tissue and the inability to achieve or maintain an erection. Furthermore, ROS impact the transmission of nitrergic neurotransmitters by causing the death of nitrergic neurons and reducing the signaling of neuronal NO synthase (nNOS), exacerbating ED. Therapeutic approaches targeting OS, including antioxidants and lifestyle modifications, show promise in ameliorating ED symptoms. The review underscores the need for further research to develop effective treatments, emphasizing the interplay between OS and vascular health in ED. Integrating pharmacological and non-pharmacological strategies could enhance clinical outcomes for ED patients, advocating for OS management in ED treatment protocols to improve patient quality of life.

• #1 Aging related erectile dysfunction—potential mechanism to halt or delay its onset – Ferrini – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/13319/html

  The apoptotic process in the penis appears to begin early in a man’s life and can be first identified by the increase in the refractory period most men will experience usually sometime around their 3rd decade of life. […] In response, the SMC begin to fight the oxidative stress and apoptosis associated with these aging related changes by producing NO from iNOS. […] Preliminary data suggest that products that upregulate this NO producing pathway and/or pharmacologically release NO, and/or protect its product, cGMP, show promise in halting or reversing the cellular changes associated with this aging process.

• #1

  https://journals.lww.com/jodb/fulltext/2020/11010/erectile_dysfunction_in_diabetes_mellitus__a.1.aspx

  The proposed mechanisms of ED in diabetic patients include elevated advanced glycation end-products and increased levels of oxygen-free radicals, impaired nitric oxide (NO) synthesis, increased endothelin B receptor binding sites and ultrastructural changes, upregulated RhoA/Rho-kinase pathway, NO-dependent selective nitrergic nerve degeneration and impaired cyclic guanosine monophosphate-dependent kinase-1. […] Diabetes causes several changes in the neuromuscular system, all of which can contribute to ED. In men with diabetes, there is good evidence that ED is due to failure of nitric oxide (NO)-induced smooth muscle relaxation due to both autonomic neuropathy endothelium dysfunction. […] The vascular endothelium in the penile vasculature produces Endothelial NO synthase eNOS, and the neuronal tissues produce neuronal NO synthase n NOS. Both these synthases transport, the NO in the corpora spongiosa smooth muscle and convert the Guanosine triphosphate into cyclic guanosine monophosphate (cGMP), with the help of an enzyme guanylate cyclase.

• #1 Erectile Dysfunction – StatPearls – NCBI BookshelfTwitterFacebookLinkedInGitHubNCBI Insights BlogTwitterFacebookYoutube

  https://www.ncbi.nlm.nih.gov/books/NBK562253/

  ED has useful independent predictive value for future cardiovascular events; therefore, screen all patients with ED for cardiovascular risks. […] The critical process in penile erection activity is the relaxation of the intracavernosal smooth muscle. This process permits increased blood flow into the corpora cavernosa, which fills with blood and compresses the emissary veins, reducing venous outflow. The paraventricular and medial preoptic nuclei of the hypothalamus control this process. Signals travel through the parasympathetic nervous system to the parasympathetic nerves of the S2-S4 sacral plexus and then to the penis via the cavernosal nerves. Nitric oxide released by the cavernous nerve terminals initiates the erectile process, while nitric oxide from endothelial cells acts to maintain it. […] Pathology arising from any of the above processes can result in erectile dysfunction.

• #1 Pathophysiology of erectile dysfunction: the contributions of trabecular structure to function and the role of functional antagonism | International Journal of Impotence Research

  https://www.nature.com/articles/3900576

  The alternate hypothesis proposes that ED is the result of a metabolic imbalance between relaxatory and contractile processes within the trabecular smooth muscle such that contractile processes predominate. […] Based on this hypothesis, therapy can be accomplished via drugs which shift this balance towards vasodilatation, or by gene therapy approaches to supplement the deficient components favoring smooth muscle relaxation. […] Both of these hypotheses predict a management strategy for ED that impacts pharmacotherapeutics. […] In this review of the pathophysiology of ED, each hypothesis will be examined and a synthesis devised incorporating both views. […] The future of research in this area as well as pharmacotherapy in ED in terms of pathophysiology is discussed including the merits and drawbacks of prophylaxis and prevention of ED.

• #1 What Is Erectile Dysfunction (ED)? – Consensus: AI Search Engine for Research

  https://consensus.app/home/blog/what-is-erectile-dysfunction-ed/

  Erectile Dysfunction (ED) is a prevalent condition characterized by the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. […] The pathogenesis of ED involves complex mechanisms, including metabolic and cardiovascular factors. In men with T2D, metabolic syndrome is associated with increased odds of ED, suggesting that metabolic mechanisms play a crucial role. Additionally, endothelial damage due to obesity and hypercaloric diets can lead to ED by affecting nitric oxide bioavailability and increasing oxidative stress. Aging is another critical factor, with studies showing that age-related changes in gene expression, such as the upregulation of IGFBP3, contribute to increased apoptosis, oxidative stress, and fibrosis in erectile tissues. […] In summary, ED is a multifaceted condition influenced by metabolic, cardiovascular, and age-related factors.

• #1 Aging related erectile dysfunction—potential mechanism to halt or delay its onset – Ferrini – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/13319/html

  Erectile dysfunction (ED) will visit every man at some time in his life. […] The most common cause of ED, regardless of the patient’s age, is vasculogenic due to CVOD or venous leakage. Pathologically, this is due to an aging related apoptosis of the corporal SMC similar to what is believed to also occur in the media of the peripheral vasculature. […] The mechanism(s) underlying this aging related loss of the normal smooth muscle within the corporal bodies is believed to be due mainly to an apoptotic process that is primarily triggered by oxidative stress. […] When about 15% of the functioning corporal smooth muscle mass has been impacted, it can lead to symptomatic ED and this theoretically can occur at any age since it is believed the apoptotic process simply due to the aging process is most likely genetically determined in each individual.

• #1 Pathogenesis of erectile dysfunction: an update.

  https://smj.journals.ekb.eg/article_340988.html

  Erectile dysfunction (ED) is a global sexual disease of males characterized by a poor impact on many aspects of the lives of both husbands and wives. […] The authors classified erectile dysfunction into two categories, one occurs in males with decreased sexual desire and the other occur with normal desire. […] As regards the aetiology of erectile dysfunction, the authors classified the causes as arteriogenic, venogenic, and neurogenic. […] The role of microRNAs in erectile dysfunction is a recent theory. […] MiRNAs have an essential role in male infertility and ED. […] The mechanisms that may explain the role of miRNA in ED include apoptosis, fibrosis, angiogenesis, and other mechanisms.

• #1 Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4613-1087-7_1

  Until recently, erectile dysfunction (ED) was treated by either sexual counseling or penile prosthesis implantation. […] With ED now amenable to pharmacologic solutions, research is continuously underway to elucidate the mechanisms underlying the pathophysiologic basis of ED. […] Studies that scrutinize the pathophysiology of ED have revealed various modulators or agents that may play a significant role in penile erection. […] These agents have been demonstrated to mediate their effects through modulation with gap junctions and potassium channels. […] There also appears to be a central control of the cardiac, respiratory, and penile functions that ultimately effects penile tumescence via an intricate cascade of coordinated events. […] With investigators striving to shed light on the pathophysiologic process of ED, the future does look bright for ED patients as more therapeutic agents, such as new oral agents and gene therapy, are on the horizon.

• #2 Erectile Dysfunction: From Pathophysiology to Clinical Assessment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-11701-5_3

  Erectile dysfunction (ED) is defined as the persistent inability to attain and/or maintain penile erection sufficient to permit satisfactory sexual performance. […] Erectile dysfunction may affect physical and physiological health and has a strong impact on quality of life and relationships. It is recognized as a possible early sign of coronary artery and peripheral vascular disease. Therefore, physicians should ask male patients about sexual health in order to identify potential life-threatening underlying conditions such as cardiovascular disease. […] ED is known to have psychological as well as organic causes. Non-organic erectile dysfunction is also known as psychogenic or adrenaline-mediated erectile dysfunction. […] Erectile dysfunction possibly generates from any process that impairs either the neural or the vascular pathways that contribute to erection. Neurogenic erectile dysfunction is caused by a deficit in nerve signaling to the corpora cavernosa.

• #2 Erectile dysfunction – Wikipedia

  https://en.wikipedia.org/wiki/Erectile_dysfunction

  Penile erection is managed by two mechanisms: the reflex erection, which is achieved by directly touching the penile shaft, and the psychogenic erection, which is achieved by erotic or emotional stimuli. The former involves the peripheral nerves and the lower parts of the spinal cord, whereas the latter involves the limbic system of the brain. In both cases, an intact neural system is required for a successful and complete erection. Stimulation of the penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of the smooth muscles of the corpora cavernosa (the main erectile tissue of the penis), and subsequently penile erection. Additionally, adequate levels of testosterone (produced by the testes) and an intact pituitary gland are required for the development of a healthy erectile system. As can be understood from the mechanisms of a normal erection, impotence may develop due to hormonal deficiency, disorders of the neural system, lack of adequate penile blood supply or psychological problems.

• #2 Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments

  https://www.mdpi.com/1467-3045/46/8/521

  The mechanisms underlying penile erection are intricate and involve a delicate balance between various physiological processes. Penile tumescence is primarily a neurovascular event regulated by the central and peripheral nervous systems. It heavily relies on the proper functioning of vascular and neural interactions. Nitric oxide (NO) plays a crucial role in these processes by facilitating smooth muscle relaxation in the corpora cavernosa, promoting vasodilation. This vasodilation is essential for the engorgement of the penis with blood. […] The literature extensively covers the physiological mechanisms of penile erection and the impact of factors like endothelial dysfunction, reduced NO availability, and increased oxidative stress on ED. Key areas well represented in the literature include the roles of neurogenic, vasculogenic, hormonal, and psychological factors in ED pathophysiology, as well as the impact of lifestyle factors such as smoking, obesity, and alcohol consumption. Vasculogenic ED often stems from endothelial dysfunction, characterized by reduced NO availability and increased oxidative stress, which impede normal blood flow to penile tissue.

• #2 Erectile Dysfunction | Conditions | UCSF Health

  https://www.ucsfhealth.org/conditions/erectile-dysfunction

  Erectile Dysfunction, or ED, is difficulty or inability to attain and maintain an erection sufficient for satisfactory sexual activity. […] The ability to have an erection requires complex coordination among nerves, blood vessels, muscles and the brain. […] A variety of factors frequently in combination can cause ED. These factors include neurological, hormonal and vascular disorders, as well as the natural aging process and certain chronic diseases. […] The cavernous nerves travel from the underside of the penis to the prostate. They regulate blood flow within the penis. In the flaccid state, relatively little blood flows in through the arteries and there is free outflow via the small veins exiting the spongy tissue just under the thick tunica. During erection, the smooth muscle in the penis relaxes while the arteries widen to bring in more blood. This expands the three cylinders of erectile tissue in the penis, thus lengthening and enlarging the penis. The expansion of these cylinders compresses the small veins, reducing the outflow of blood.

• #2 Erectile Dysfunction Part I: pathophysiology and risk factors | Urology News

  https://www.urologynews.uk.com/features/synopsis/post/erectile-dysfunction-part-i-pathophysiology-and-risk-factors

  Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erection, which is adequate for satisfactory sexual intercourse. […] ED is commonly divided into either psychogenic or organic causes. However in many patients the disorder is of mixed aetiology with both factors contributing. […] ED associated with diabetes and vascular disease is a result of endothelial dysfunction and neurogenic injury. […] Moreover, endothelial dysfunction is a reflection of the loss of NO activity or biosynthesis at the endothelial level. […] The association between metabolic syndrome, insulin resistance and obesity and ED in men is now well characterised and understood. […] Erectile dysfunction is often a combination of organic and psychogenic causes. […] Nitric oxide (NO) is the principal neurotransmitter. […] Erectile dysfunction is a manifestation of endothelial dysfunction.

• #2 Vasculogenic ED (Erectile Dysfunction) Program | UH Harrington Heart & Vascular Institute | University Hospitals | Cleveland, Ohio | University Hospitals

  https://www.uhhospitals.org/services/heart-and-vascular-services/conditions-and-treatments/vascular-disease/vasculogenic-erectile-dysfunction-program

  Vasculogenic erectile dysfunction (ED) is a condition in which a man experiences the recurring inability to achieve or maintain an erection sufficient for sexual intercourse due to disease in the arteries and/or veins that supply blood to and from the penis. […] Organic causes of ED are subdivided into vasculogenic, neurogenic and hormonal types. Representing the most common type of ED overall, vasculogenic ED occurs when the arteries and/or veins that bring blood to and from the penis, respectively, are not functioning correctly due to blockages, narrowing or other physiological causes. […] Arteriogenic ED, or arterial ED, occurs when atherosclerosis (buildup of cholesterol plaque in arteries) causes a blockage in one more of the arteries that supply blood to the penis. […] Venogenic ED also called venous ED, VED, venous leak or venous leak syndrome is when the inflow of arterial blood flow to the penis is sufficient, but outgoing blood drains too rapidly from the erectile tissue to maintain a normal erection for the duration of sexual intercourse.

• #2 Erectile Dysfunction and Heart Disease | Brown University Health

  https://www.lifespan.org/be-well/erectile-dysfunction-and-heart-disease

  Erectile dysfunction (ED) is defined as the inability for a man to attain and maintain an erection rigid enough for sex. […] As men age, the problem is most often due to poor blood flow, and this pattern is known as vasculogenic ED. Vasculogenic ED is often the very first sign of a change in cardiovascular health and precedes the onset of a significant cardiovascular event, such as a heart attack, by 3 to 5 years. […] Endothelial dysfunction is also the first step in the buildup of cholesterol plaque in the coronary arteries and is the link between ED and cardiovascular disease. […] New studies show that men with ED at any age have a higher risk of heart attack or stroke. […] Men presenting with ED should have an assessment of the common risks for cardiovascular disease like high blood pressure, elevated cholesterol levels, diabetes, and smoking.

• #2 Erectile dysfunction | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/erectile-dysfunction?lang=us

  End-diastolic velocity is the best Doppler indicator of venogenic impotence. Its value 5 cm/sec indicates venous dysfunction. A good diastolic reversal virtually rules out venous insufficiency. […] Angiography with selective internal iliac angiography is the gold standard for arteriogenic impotence. However, it is invasive and not recommended for screening or primary diagnosis.

• #2 Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments

  https://www.mdpi.com/1467-3045/46/8/521

  Oxidative stress, primarily due to the accumulation of reactive oxygen species (ROS), impairs endothelial function, reduces NO bioavailability, and promotes vascular dysfunction, which conditions all amount to key mechanisms in ED onset and progression. Recent studies have emphasized the significance of endogenous antioxidants in maintaining penile health and mitigating oxidative stress. Antioxidants, including enzymes like superoxide dismutase (SOD), catalase, and molecules such as glutathione, are vital in maintaining NO bioavailability. Their effect is primarily achieved through shielding NO from being scavenged by superoxide radicals. […] Despite the existing body of literature, there are gaps and conflicting findings regarding the role of oxidative stress and the effectiveness of antioxidant therapies in ED. This article aims to fill these gaps by providing a comprehensive review of the current literature on the role of oxidative stress in ED, its impact on endothelial and neural function, and potential therapeutic interventions targeting oxidative stress.

• #2

  https://journals.lww.com/ijoru/fulltext/2024/02010/etiology,_surgical_anatomy,_and_pathophysiology_of.2.aspx

  Organic ED can further be subdivided into vasculogenic (arteriogenic, cavernosal, and mixed), neurogenic, endocrinologic, anatomic, and drug-induced ED. […] There is a strong correlation between CVD and ED, and often ED can be the first sign of CVD. […] Therefore, any pathology interfering with NO signaling will compromise erectile function, as vascular disease is highly correlated with impaired NO signaling. […] The pathophysiology of ED can be categorized into psychogenic and organic. Psychogenic ED can either be generalized, often secondary to age-related libido decrease, or situational (partner or performance-related). […] Many classifications of ED have been published. […] The most common medications that have proven to induce ED include diuretics, alpha-blockers, antipsychotics, antiandrogens, statins, and recreational drugs, such as anabolic steroids, cocaine, and alcohol. […] Despite major advances in the knowledge of ED etiology and physiopathology, there remain areas to be addressed to improve the current state of knowledge.

• #2 The Central Mechanisms of Sexual Function » Sexual Medicine » BUMC

  https://www.bumc.bu.edu/sexualmedicine/publications/the-central-mechanisms-of-sexual-function/

  Many regions in the brain contribute to male sexual response, ranging from centers in the hindbrain that also regulate basic body functions such as breathing, to areas in the cerebral cortex, the organ that controls higher thought and intellect. […] Switching off the activity of the sympathetic nervous system enhances erections. […] Some erections may be generated entirely by the spinal cord. […] Observations of men and laboratory animals with spinal cord damage indicate that when the brain is disconnected from the erection-generating center in the spinal cord, erections generally occur more often and with less tactile stimulation than before the injury. […] This discovery may have important implications for people who take drugs that enhance levels of serotonin, such as the selective serotonin reuptake inhibitors (SSRIs) that are used to treat depression and other mental health disorders.

• #2 β-Blockers and Erectile Dysfunction in Heart Failure. Between Myth and Reality

  https://www.imrpress.com/journal/RCM/23/5/10.31083/j.rcm2305173/htm

  Furthermore, throughout their effect on luteinizing hormone, β-blockers might induce a depression of Leydig cell activity leading a reduction in testosterone levels, which have been demonstrated to be necessary for maintenance of intra-penile NO synthase levels. […] Since 1980s, several studies tried to assess a possible negative effect of different β-blockers on erectile function in men with essential hypertension, their results being highly controversial. […] Nonetheless, it should be also cited an interesting study by Silvestri and colleagues which highlighted that the prejudice about this particular potential adverse effect of β-blockers therapy may itself result in ED through a mere psychological effect (i.e., Hawtorne effect). […] Most of the medications commonly used in HF therapy have been associated with sexual dysfunction but, again, data specifically obtained in such a population are lacking.

• #2 Aging related erectile dysfunction—potential mechanism to halt or delay its onset – Ferrini – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/13319/html

  Erectile dysfunction (ED) will visit every man at some time in his life. […] The most common cause of ED, regardless of the patient’s age, is vasculogenic due to CVOD or venous leakage. Pathologically, this is due to an aging related apoptosis of the corporal SMC similar to what is believed to also occur in the media of the peripheral vasculature. […] The mechanism(s) underlying this aging related loss of the normal smooth muscle within the corporal bodies is believed to be due mainly to an apoptotic process that is primarily triggered by oxidative stress. […] When about 15% of the functioning corporal smooth muscle mass has been impacted, it can lead to symptomatic ED and this theoretically can occur at any age since it is believed the apoptotic process simply due to the aging process is most likely genetically determined in each individual.

• #2 Aging related erectile dysfunction—potential mechanism to halt or delay its onset – Ferrini – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/13319/13808

  Erectile dysfunction (ED) will visit every man at some time in his life. […] The most common cause of ED, regardless of the patient’s age, is vasculogenic due to CVOD or venous leakage. […] The apoptotic process in the penis appears to begin early in a man’s life and can be first identified by the increase in the refractory period most men will experience usually sometime around their 3rd decade of life. […] The progression of this increase in the refractory period over time will reach a stage, depending on the patient’s genetics and co-morbidities, where maintenance of the erection becomes problematic and symptomatic ED is apparent. […] In response, the SMC begin to fight the oxidative stress and apoptosis associated with these aging related changes by producing NO from iNOS. […] Preliminary data suggest that products that upregulate this NO producing pathway and/or pharmacologically release NO, and/or protect its product, cGMP, show promise in halting or reversing the cellular changes associated with this aging process.

• #2 Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments

  https://www.mdpi.com/1467-3045/46/8/521

  Erectile dysfunction (ED) is a prevalent condition affecting men’s sexual health, with oxidative stress (OS) having recently been identified as a significant contributing causative factor. This narrative review aims to elucidate the role of OS in the pathophysiology of ED, focusing on impact, mechanisms, and potential therapeutic interventions. Key findings indicate that OS disrupts endothelial function and nitric oxide (NO) signaling, crucial for erectile function. Various sources of reactive oxygen species (ROS) and their detrimental effects on penile tissue are discussed, including aging, diabetes mellitus, hypertension, hyperlipidemia, smoking, obesity, alcohol consumption, psychological stress, hyperhomocysteinemia, chronic kidney disease, and sickle cell disease. Major sources of ROS, such as NADPH oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), and mitochondrial electron transport, are identified. NO is scavenged by these ROS, leading to endothelial dysfunction characterized by reduced NO availability, impaired vasodilation, increased vascular tone, and inflammation. This ultimately results in ED due to decreased blood flow to penile tissue and the inability to achieve or maintain an erection. Furthermore, ROS impact the transmission of nitrergic neurotransmitters by causing the death of nitrergic neurons and reducing the signaling of neuronal NO synthase (nNOS), exacerbating ED. Therapeutic approaches targeting OS, including antioxidants and lifestyle modifications, show promise in ameliorating ED symptoms. The review underscores the need for further research to develop effective treatments, emphasizing the interplay between OS and vascular health in ED. Integrating pharmacological and non-pharmacological strategies could enhance clinical outcomes for ED patients, advocating for OS management in ED treatment protocols to improve patient quality of life.

• #2

  https://apcz.umk.pl/QS/article/view/53372

  Diabetes mellitus (DM) significantly increases the risk of erectile dysfunction (ED), affecting up to 52% of diabetic males. […] Key factors influencing ED in this population include poor glycemic control, obesity, hypertension, and the duration of diabetes. […] Effective management of ED in diabetic patients requires optimal glycemic control and lifestyle modifications such as diet, exercise, and weight management. […] Pharmacological treatments involve phosphodiesterase type 5 (PDE5) inhibitors like sildenafil, tadalafil, and vardenafil, which enhance erectile function by increasing cGMP levels. […] Emerging therapies like mesenchymal stem cell therapy and novel drug combinations offer promising avenues, focusing on cellular regeneration and improved vascular function. […] Despite the availability of these treatments, ED remains underreported due to patient embarrassment and healthcare provider hesitation, underscoring the need for increased awareness and proactive management. […] As projections indicate a rising global prevalence of ED, integrating ED management into comprehensive diabetes care is essential to enhance patient quality of life and address this significant public health issue.

• #2 Erectile Dysfunction (ED) Guideline – American Urological Association

  https://www.auanet.org/guidelines-and-quality/guidelines/erectile-dysfunction-(ed)-guideline

  The degree of ED strongly correlates with severity of CVD, and recent studies suggest that ED may be considered a sentinel marker in men with occult CVD. […] Symptoms of ED may precede a cardiovascular event by up to five years. […] The increased number of men with CVD risk factors is paralleled by the worldwide increase in the prevalence of ED. […] For men with ED, morning serum total testosterone levels should be measured. […] For men with ED, penile venous surgery is not recommended. […] For men with ED, low-intensity extracorporeal shock wave therapy (ESWT) should be considered investigational. […] For men with ED, intracavernosal stem cell therapy should be considered investigational. […] For men with ED, platelet-rich plasma (PRP) therapy should be considered experimental.

• #2 What Is Erectile Dysfunction (ED)? – Consensus: AI Search Engine for Research

  https://consensus.app/home/blog/what-is-erectile-dysfunction-ed/

  Erectile Dysfunction (ED) is a prevalent condition characterized by the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. […] The pathogenesis of ED involves complex mechanisms, including metabolic and cardiovascular factors. In men with T2D, metabolic syndrome is associated with increased odds of ED, suggesting that metabolic mechanisms play a crucial role. Additionally, endothelial damage due to obesity and hypercaloric diets can lead to ED by affecting nitric oxide bioavailability and increasing oxidative stress. Aging is another critical factor, with studies showing that age-related changes in gene expression, such as the upregulation of IGFBP3, contribute to increased apoptosis, oxidative stress, and fibrosis in erectile tissues. […] In summary, ED is a multifaceted condition influenced by metabolic, cardiovascular, and age-related factors.

• #2

  https://journals.lww.com/ijoru/fulltext/2024/02010/etiology,_surgical_anatomy,_and_pathophysiology_of.2.aspx

  Erectile dysfunction (ED) is a result of complex pathophysiological, anatomical, and molecular pathways processes. Understanding the mechanisms of ED in depth is essential to provide evidence-based patient care. […] The etiology of ED is multifactorial, with risk factors overlapping those of cardiovascular diseases (CVD), such as smoking, obesity, diabetes, metabolic syndrome, sedentary lifestyles, and hyperlipidemia. ED is the result of very complex neuronal, vascular, and hormonal signaling disruptions. Key neurotransmitters, endothelial, and vascular function of the corpus cavernosum have been identified. […] The pathways from sexual arousal to penile erection are generated by complex pathophysiological processes involving the corticolimbic system, and molecular biological mechanisms. This study will explore the etio-pathophysiology of ED, which encompasses vasculogenic, neurogenic, hormonal, systemic, psychogenic, and molecular involvement.

• #2 Erectile Dysfunction and Peyronie’s Disease – Medical Clinical Policy Bulletins | Aetna

  https://www.aetna.com/cpb/medical/data/1_99/0007.html

  The authors concluded that the identified fibrosis-related gene signature may serve as the novel biomarkers for the treatment of DMED. […] The authors concluded that the findings of this meta-analysis suggested that the effectiveness of stem cell-derived exosomes for ED; exosomes may restore erectile function by optimizing cavernosum microstructures. […] The authors concluded that the use of RxPTT beginning 1 month post-prostatectomy results in improved penile length and erectile function, with benefits maintained after discontinuing therapy.

• #3 Erectile Dysfunction (ED) Guideline – American Urological Association

  https://www.auanet.org/guidelines-and-quality/guidelines/erectile-dysfunction-(ed)-guideline

  The degree of ED strongly correlates with severity of CVD, and recent studies suggest that ED may be considered a sentinel marker in men with occult CVD. […] Symptoms of ED may precede a cardiovascular event by up to five years. […] The increased number of men with CVD risk factors is paralleled by the worldwide increase in the prevalence of ED. […] For men with ED, morning serum total testosterone levels should be measured. […] For men with ED, penile venous surgery is not recommended. […] For men with ED, low-intensity extracorporeal shock wave therapy (ESWT) should be considered investigational. […] For men with ED, intracavernosal stem cell therapy should be considered investigational. […] For men with ED, platelet-rich plasma (PRP) therapy should be considered experimental.

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