Most current studies believe that ED is mainly caused by organic factors (neurogenic, vascular, diabetic, etc. ), psychological factors (performance anxiety, stress, and mental disorders), iatrogenic factors (caused by surgical injury), and increasing age (aging) (; ; Wang, 2011; Shridharani and Brant, 2016). At present, the clinical diagnosis methods of ED mainly include questionnaire surveys, psychological assessments, laboratory, and equipment examinations (Xiong et al., 2022).
Some experts believe that clinicians should first conduct a comprehensive and targeted physical examination and questionnaire survey for patients with suspected ED (Zhang et al., 2014). The comprehensive questionnaire survey is the primary condition to help doctors diagnose ED and decide on the treatment plan.
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The most widely used questionnaire to evaluate male sexual function is the International Index of Erectile Function (IIEF)-5 (Vickers et al., 2020). Currently, the treatment methods for ED mainly include lifestyle adjustment, psychotherapy, drug therapy, physical therapy, and surgical therapy (). However, the effect of lifestyle adjustment therapy is not obvious in the treatment of ED, and there is a lack of interventional studies (Yafi et al., 2016). The high cost of counseling and the uncertainty of efficacy of psychotherapy pose difficulties for most patients (). Because each person’s anxiety factors are different, there are no standardized protocols for psychosomatic pharmacological treatment of ED (). The efficacy of drug therapy is currently positive, but some patients do not respond to the drug, such as patients with severe vascular ED, diabetic ED or neurogenic ED. Besides, some adverse effects also limit the application of drug therapy in ED patients (). Few patients choose surgical therapy because of the high cost and risks.
Taking prosthetic implants for example, it costs more than $20,000 and have a high risk of infection (Stephenson et al., 2005). Therefore, physical therapy has become the choice of more and more ED patients because the relatively certain efficacy and the acceptable cost. Given the increasing prevalence and low overall diagnosis rate of ED, we review the pathophysiological mechanism as well as the benefits and drawbacks of standard clinical diagnostic equipment and physical therapy device for ED in order to give physicians a better systematic understanding of the diagnosis and physical treatment of ED. The central regulation of erectile involves various primary afferents, spinal interneurons, sympathetic nerves, parasympathetic nerves, and so on (). Neurological disorders may lead to abnormalities in the endocrine system or the cardiovascular system, which can affect sexual function (). Approximately 10%–19% of the etiology of ED can be classified as neuropathy, which may be central, peripheral, or both ().
Most current studies believe that ED is mainly caused by organic factors (neurogenic, vascular, diabetic, etc. ), psychological factors (performance anxiety, stress, and mental disorders), iatrogenic factors (caused by surgical injury), and increasing age (aging) (; ; Wang, 2011; Shridharani and Brant, 2016). At present, the clinical diagnosis methods of ED mainly include questionnaire surveys, psychological assessments, laboratory, and equipment examinations (Xiong et al., 2022). Some experts believe that clinicians should first conduct a comprehensive and targeted physical examination and questionnaire survey for patients with suspected ED (Zhang et al., 2014). The comprehensive questionnaire survey is the primary condition to help doctors diagnose ED and decide on the treatment plan.
The most widely used questionnaire to evaluate male sexual function is the International Index of Erectile Function (IIEF)-5 (Vickers et al., 2020). Currently, the treatment methods for ED mainly include lifestyle adjustment, psychotherapy, drug therapy, physical therapy, and surgical therapy (). However, the effect of lifestyle adjustment therapy is not obvious in the treatment of ED, and there is a lack of interventional studies (Yafi et al., 2016). The high cost of counseling and the uncertainty of efficacy of psychotherapy pose difficulties for most patients (). Because each person’s anxiety factors are different, there are no standardized protocols for psychosomatic pharmacological treatment of ED ().
The efficacy of drug therapy is currently positive, but some patients do not respond to the drug, such as patients with severe vascular ED, diabetic ED or neurogenic ED. Besides, some adverse effects also limit the application of drug therapy in ED patients (). Few patients choose surgical therapy because of the high cost and risks. Taking prosthetic implants for example, it costs more than $20,000 and have a high risk of infection (Stephenson et al., 2005). Therefore, physical therapy has become the choice of more and more ED patients because the relatively certain efficacy and the acceptable cost. The erection process requires stimulation of ed gels the hypothalamus received by the tactile, visual, and auditory sense organs followed by signals transmitted by neurons. This process may require an entire neural pathway (autonomic nervous system), so damage to any point in that neural pathway that disrupts the transmission of signals may result in ED (). () proved that peripheral neuropathy affected male erectile function to some extent, and they mentioned the highly overlapping relationship among peripheral neuropathy, ED, and cardiovascular diseases, which proved that peripheral neuropathy was a new risk factor of ED. Neuropathy can also be caused by being overweight, studies have shown that compared with normal weight, obesity in peripheral neuropathy (especially small nerve fibers lesions) is the more common form, Herman et al. () confirmed that corneal nerve fiber density and length are associated with the diagnosis of ED, but has no obvious relation with the severity of ED. Neurological injury due to trauma can also cause ED, depending on the degree of neurological injury and the integrity of the nerve. Trauma can cause damage to the cavernous nerve, the axonal density and conduction velocity of this nerve will be reduced, which leads to the occurrence of ED (Yin et al., 2013). Sympathetic and parasympathetic nerves are involved in the erection process of the penis, emanating from the lumbar spine and sacral root.
This nerve injury induces protein 1, Ninjurin-1, to participate in the neuroinflammatory response, which resulted in ED (Yin et al., 2013). Long-term postoperative complications of colorectal surgery due to autonomic nerve injury in the pelvis also include ED (). In a prospective study of 50 subjects by Hande Gokce, the incidence of ED after rectal cancer surgery was found to be about 10%–35%. The etiology of these ED patients vardenafil 5 mg is considered to be related to vascular nerve damage during the rectal surgery.(). Diabetes mellitus is a metabolic disease with hyperglycemia caused by defective insulin secretion, defective insulin action, or both () (Figure 1).
Persistently high blood glucose levels can lead to nerve and blood vessel damage, cardio-cerebral circulatory complications, and even death (). Diabetes is considered as a major risk factor for ED, and the association between diabetes and the development of ED has been documented in animal models and humans since 1970 (). Chronic hyperglycemia may lead to impaired nitric oxide (NO) synthesis and cycloguanosine monophosphate (cGMP) pathway, increased reactive free radical level, upregulated of RhoA/Rho kinase pathway, and damaged nerve function, which may be the mechanisms of ED in diabetic patients (). The persistent state of hyperglycemia will lead to an increase in advanced glycation end products (AGEs), which are the final products of amino non-enzymatic glycation of proteins, lipids, and nucleic acids in human tissues. Increased expression of AGEs in the corpus cavernosum of diabetic patients may lead to changes in tissue structure, such as thickened vascular walls, decreased elasticity, endothelial dysfunction, and atherosclerosis.
This process can produce overloaded peroxynitrite, which can lead to oxidative damage to a number of important biomolecules, resulting in ED (Trebaticky et al., 2019). Some researchers believe that the occurrence of ED in patients with diabetes is related to the reduction of cGMP and the impaired relaxation of cavernosal smooth muscle due to the oxygen free radicals produced by AGEs induced related cellular oxidative damage and the quenching of NO (Thorve et al., 2011). Nerve damage caused by chronic hyperglycemia can affect different sensory patterns as well as autonomic function (Sharma et al., 2020). Some sensory diagnostic devices can be used to evaluate sensory functions such as vibration perception, pressure perception, and heat perception, so as to improve diagnostic sensitivity in clinical practice (). Morning testosterone levels can also be used as an auxiliary diagnosis method of diabetic ED. Damage to these nerves blocks the conduction of corresponding nerve signals, directly leading to ED (). ED is involved in many surgical complications in clinical practice. For example, one of the most common complications after radical prostatectomy is ED, which is usually caused by intraoperative injury of the cavernous nerve (). This nerve injury induces protein 1, Ninjurin-1, to participate in the neuroinflammatory response, which resulted in ED (Yin et al., 2013). Long-term postoperative complications of colorectal surgery due to autonomic nerve injury in the pelvis also include ED (). In a prospective study of 50 subjects by Hande Gokce, the incidence of ED after rectal cancer surgery was found to be about 10%–35%.
The etiology of these ED patients vardenafil 5 mg is considered to be related to vascular nerve damage during the rectal surgery.(). Diabetes mellitus is a metabolic disease with hyperglycemia caused by defective insulin secretion, defective insulin action, or both () (Figure 1). Persistently high blood glucose levels can lead to nerve and blood vessel damage, cardio-cerebral circulatory complications, and even death (). Diabetes is considered as a major risk factor for ED, and the association between diabetes and the development of ED has been documented in animal models and humans since 1970 (). Chronic hyperglycemia may lead to impaired nitric oxide (NO) synthesis and cycloguanosine monophosphate (cGMP) pathway, increased reactive free radical level, upregulated of RhoA/Rho kinase pathway, and damaged nerve function, which may be the mechanisms of ED in diabetic patients (). The persistent state of hyperglycemia will lead to an increase in advanced glycation end products (AGEs), which are the final products of amino non-enzymatic glycation of proteins, lipids, and nucleic acids in human tissues. Increased expression of AGEs in the corpus cavernosum of diabetic patients may lead to changes in tissue structure, such as thickened vascular walls, decreased elasticity, endothelial dysfunction, and atherosclerosis. This process can produce overloaded peroxynitrite, which can lead to oxidative damage to a number of important biomolecules, resulting in ED (Trebaticky et al., 2019). Some researchers believe that the occurrence of ED in patients with diabetes is related to the reduction of cGMP and the impaired relaxation of cavernosal smooth muscle due to the oxygen free radicals produced by AGEs induced related cellular oxidative damage and the quenching of NO (Thorve et al., 2011). Nerve damage caused by chronic hyperglycemia can affect different sensory patterns as well as autonomic function (Sharma et al., 2020). Some sensory diagnostic devices can be used to evaluate sensory functions such as vibration perception, pressure perception, and heat perception, so as to improve diagnostic sensitivity in clinical practice ().
Given the increasing prevalence and low overall diagnosis rate of ED, we review the pathophysiological mechanism as well as the benefits and drawbacks of standard clinical diagnostic equipment and physical therapy device for ED in order to give physicians a better systematic understanding of the diagnosis and physical treatment of ED. The central regulation of erectile involves various primary afferents, spinal interneurons, sympathetic nerves, parasympathetic nerves, and so on (). Neurological disorders may lead to abnormalities in the endocrine system or the cardiovascular system, which can affect sexual function (). Approximately 10%–19% of the etiology of ED can be classified as neuropathy, which may be central, peripheral, or both (). The erection process requires stimulation of ed gels the hypothalamus received by the tactile, visual, and auditory sense organs followed by signals transmitted by neurons.
This process may require an entire neural pathway (autonomic nervous system), so damage to any point in that neural pathway that disrupts the transmission of signals may result in ED (). () proved that peripheral neuropathy affected male erectile function to some extent, and they mentioned the highly overlapping relationship among peripheral neuropathy, ED, and cardiovascular diseases, which proved that peripheral neuropathy was a new risk factor of ED. Neuropathy can also be caused by being overweight, studies have shown that compared with normal weight, obesity in peripheral neuropathy (especially small nerve fibers lesions) is the more common form, Herman et al. () confirmed that corneal nerve fiber density and length are associated with the diagnosis of ED, but has no obvious relation with the severity of ED. Neurological injury due to trauma can also cause ED, depending on the degree of neurological injury and the integrity of the nerve.
Trauma can cause damage to the cavernous nerve, the axonal density and conduction velocity of this nerve will be reduced, which leads to the occurrence of ED (Yin et al., 2013). Sympathetic and parasympathetic nerves are involved in the erection process of the penis, emanating from the lumbar spine and sacral root. Damage to these nerves blocks the conduction of corresponding nerve signals, directly leading to ED (). ED is involved in many surgical complications in clinical practice. For example, one of the most common complications after radical prostatectomy is ED, which is usually caused by intraoperative injury of the cavernous nerve (). Morning testosterone levels can also be used as an auxiliary diagnosis method of diabetic ED. Diabetes-associated ED patients often have low morning testosterone level ().
Diabetes-associated ED patients often have low morning testosterone level (). However, diabetes is not the unique etiology cenforce 200 uk of low testosterone levels, therefore, it is critical to identify other diseases that can affect testosterone levels, such as endocrine disorders and urinary system diseases.(). ED can be caused by a variety of vascular factors, such as atherosclerosis, arterial injury, and stenosis, penile venous fistula (; Sayadi et al., 2021; Wang et al., 2021). The role of monocyte/macrophage accumulation in vascular disease is not negligible (; ). Macrophages can stimulate plaque formation in blood vessels and play an important role in vascular injury ().
Abnormal lipid metabolism and monocyte/macrophage interactions can also accelerate the formation of atherosclerotic plaques, which is closely related to the development of ED (Randrup et al., 2015). It has been shown that macrophages can affect endothelial function through macrophage-derived myeloperoxidase (MPO) - dependent ox-LDL (Mox-LDL) (). MPO can promote impaired endothelial function and intravascular plaque instability, and Mox-LDL can stimulate macrophages to produce reactive oxygen species (ROS) and secrete cytokines to affect endothelial function (). Endothelial damage may alter the state of blood flow within them, which in turn leads to ED (Salvio et al., 2021). () showed that vasogenic ED preceded coronary heart disease in younger ED patients.
The pathology of arterial ED is atherosclerosis of the internal pudendal artery, which prevents the corpus cavernosa from receiving sufficient blood flow to achieve erectile status (). Studies have shown that as vascular smooth muscle cells proliferate, collagen and fibrosis increase, leading to the thickening of the vessel wall and narrowing of the lumen. This made a decrease in blood flow to the penis, and resulted in ED (). The main diagnostic methods of vascular ED include color dual Doppler ultrasound, selective penile angiography, magnetic resonance imaging, and intravascular injection of vasoactive drugs (). Psychological problems such as anxiety, stress, and mental disorders can significantly affect the development of ED (Tan et al., 2012), there is a higher risk of ED in people with psychosis who are at very high risk (). However, diabetes is not the unique etiology cenforce 200 uk of low testosterone levels, therefore, it is critical to identify other diseases that can affect testosterone levels, such as endocrine disorders and urinary system diseases.(). ED can be caused by a variety of vascular factors, such as atherosclerosis, arterial injury, and stenosis, penile venous fistula (; Sayadi et al., 2021; Wang et al., 2021). The role of monocyte/macrophage accumulation in vascular disease is not negligible (; ).
Macrophages can stimulate plaque formation in blood vessels and play an important role in vascular injury (). Abnormal lipid metabolism and monocyte/macrophage interactions can also accelerate the formation of atherosclerotic plaques, which is closely related to the development of ED (Randrup et al., 2015).
| Therapy | Description | Status |
|---|---|---|
| Low-Intensity Shockwave Therapy | Promotes blood vessel regeneration | Experimental/clinics |
| Stem Cell Therapy | Regenerates damaged tissues in penis | Experimental |
| Platelet-Rich Plasma (PRP) | Uses patient's blood to improve tissue healing | Experimental |
| Gene Therapy | Targets genetic causes of ED | Under research |
It has been shown that macrophages can affect endothelial function through macrophage-derived myeloperoxidase (MPO) - dependent ox-LDL (Mox-LDL) (). MPO can promote impaired endothelial function and intravascular plaque instability, and Mox-LDL can stimulate macrophages to produce reactive oxygen species (ROS) and secrete cytokines to affect endothelial function (). Endothelial damage may alter the state of blood flow within them, which in turn leads to ED (Salvio et al., 2021). () showed that vasogenic ED preceded coronary heart disease in younger ED patients. The pathology of arterial ED is atherosclerosis of the internal pudendal artery, which prevents the corpus cavernosa from receiving sufficient blood flow to achieve erectile status (). Studies have shown that as vascular smooth muscle cells proliferate, collagen and fibrosis increase, leading to the thickening of the vessel wall and narrowing of the lumen.
Various psychotropic drugs are widely used in young adults with psychosis-related ED. Some studies have shown that some antipsychotic drugs can affect the dopamine D2 receptor pathway, which in turn affects erectile function. verified that psychological problems such as low self-esteem, emotional retardation, and sleep disorders not only directly affected the sexual function of patients, but also showed that the severity of mental problems was positively correlated with the severity of ED (). This made a decrease in blood flow to the penis, and resulted in ED (). The main diagnostic methods of vascular ED include color dual Doppler ultrasound, selective penile angiography, magnetic resonance imaging, and intravascular injection of vasoactive drugs (). Psychological problems such as anxiety, stress, and mental disorders can significantly affect the development of ED (Tan et al., 2012), there is a higher risk of ED in people with psychosis who are at very high risk (). Various psychotropic drugs are widely used in young adults with psychosis-related ED.
Some studies have shown that some antipsychotic drugs can affect the dopamine D2 receptor pathway, which in turn affects erectile function. verified that psychological problems such as low self-esteem, emotional retardation, and sleep disorders not only directly affected the sexual function of patients, but also showed that the severity of mental problems was positively correlated with the severity of ED ().
