madman
Super Moderator
The Impact of Testosterone on Erectile Function (2022)
Jessica N. Schardein, and James M. Hotaling
Abstract
Erectile function is dependent on the correct balance of vasoactive substances, neurotransmitters, endocrine factors, and tissue fibroelastic properties. Erectile dysfunction (ED) is a multifactorial condition that results from an imbalance of any of the factors that contribute to maintaining proper erectile function. In animal and human studies, hypogonadism has been found to interfere with the proper synthesis and/or release of enzymes as well as the tissue structure and function in the corpora cavernosa leading to ED. Restoring testosterone levels can improve erectile function for hypogonadal men with ED. Combination therapy with testosterone and phosphodiesterase-5 inhibitors has the potential to improve parameters for a greater number of patients struggling with ED who have comorbidities and do not respond to either treatment alone. When used in the appropriate clinical scenario, testosterone therapy can be a safe and effective treatment option for ED.
Introduction
An erection is a neuropsychological and hormone-mediated vascular event triggered by sensorial or direct stimulation.1 The process is dependent on the correct balance of vasoactive substances, neurotransmitters, endocrine factors, and tissue fibroelastic properties.2 The vascular reaction is achieved by increased blood flow in the paired corpora and decreased outflow that leads to increased intracavernosal pressure and volume.3
Nitric oxide (NO) is the major mediator of smooth muscle relaxation in the cavernosal arteries and trabecular muscle that leads to an increase in cyclic guanosine monophosphate (cGMP) levels, which is ultimately degraded by phosphodiesterase-5 (PDE-5).4 Sexual desire may precede and encourage sexual activity, or it may be in response to sexual stimulation, with the downstream effects described. Those who have the desire to engage in sexual acts are more likely to be distressed when there is impairment in erectile function and pursue treatment.
Erectile dysfunction (ED) occurs when a man is unable to attain or maintain a sufficient erection for sexual intercourse.5 The International Index of Erectile Function (IIEF) is a standardized questionnaire that assesses a man’s ability to initiate, maintain, or complete sexual intercourse.6 Specifically, the IIEF-erectile function (IIEF-EF) domain includes six questions that evaluate the frequency and hardness of erections, penetration during intercourse, maintenance of an erection during intercourse, ability to maintain an erection to completion of intercourse, and a man’s confidence in their ability to get and maintain an erection to determine the severity of ED from mild to severe.6
The ED more commonly affects men of increasing age with *10% of men 20–30 years old and as many as 70% of men older than 70 years being diagnosed with ED.7–9 The etiology is related to aging and vascular, neurogenic, psychological, and hormonal components.10 Medications can also impact sexual functioning and erectile response. The pathogenesis, while multifactorial, has been linked to poor psychological status, arterial endothelial damage, and low testosterone.11,12
Hypogonadism is generally defined as low testosterone with symptoms and/or signs, including weakness, fatigue, decreased energy, low libido, reduced muscle and bone mass, and increased abdominal fat.13 In general, proposed cutoffs used to define hypogonadism are <300–400 ng/dL or <8–12 nmol/L.13 Based on varying definitions, the prevalence of hypogonadism in men with ED ranges from 1.7% to 35%.14–17 The American Urology Association (AUA) guidelines recommend the evaluation of testosterone in men with ED to determine whether hypogonadism could be influencing the disease process.18
The ED in patients with low testosterone may be due to low libido and/or changes in corpora cavernosa structure and function at the cellular level from hypogonadism.19 Hypogonadism can be associated with aging and medical conditions such as obesity, hyperlipidemia, metabolic syndrome, diabetes, hypertension, and coronary artery disease (CAD).1 Testosterone replacement therapy with or without PDE-5 inhibitors is an option to restore testosterone to normal levels and improve erectile function.
Testosterone and Sexual Function
-Animal studies
-Human studies
-Special populations
-Metabolic syndrome and type 2 diabetes
-Cardiovascular disease
Testosterone Replacement
-Testosterone monotherapy
-Combination therapy with testosterone replacement and PDE-5 inhibitors
-Special population considerations
-Management
-Treatment initiation. Although patients may exhibit
-Formulation selection
-Alternatives
-Monitoring
-Limitations: Complications and side effects
Conclusion
Both animal and human studies support an association between hypogonadism and ED. Animal studies first elucidated testosterone’s role in maintaining the proper synthesis and/or release of enzymes as well as tissue structure and function in the corpora cavernosa. When low testosterone is present in both animals and humans, erectile function is compromised as a result, which can be improved with testosterone replacement.
Testosterone monotherapy in hypogonadal men without significant comorbidities can improve erectile function in those struggling with ED. Combination therapy with testosterone and PDE-5 inhibitors can lead to improvement in erectile function for hypogonadal men with medical comorbidities who do not respond to monotherapy. Based on the evidence, it is important to screen all men with ED for hypogonadism, especially those with a history of inadequate response to PDE-5 inhibitors, so that the appropriate treatment plan is implemented. Further studies are crucial to better understand the nuances of testosterone treatment for patients with different degrees of hypogonadism and to optimize sexual outcomes in hypogonadal men with ED.
Jessica N. Schardein, and James M. Hotaling
Abstract
Erectile function is dependent on the correct balance of vasoactive substances, neurotransmitters, endocrine factors, and tissue fibroelastic properties. Erectile dysfunction (ED) is a multifactorial condition that results from an imbalance of any of the factors that contribute to maintaining proper erectile function. In animal and human studies, hypogonadism has been found to interfere with the proper synthesis and/or release of enzymes as well as the tissue structure and function in the corpora cavernosa leading to ED. Restoring testosterone levels can improve erectile function for hypogonadal men with ED. Combination therapy with testosterone and phosphodiesterase-5 inhibitors has the potential to improve parameters for a greater number of patients struggling with ED who have comorbidities and do not respond to either treatment alone. When used in the appropriate clinical scenario, testosterone therapy can be a safe and effective treatment option for ED.
Introduction
An erection is a neuropsychological and hormone-mediated vascular event triggered by sensorial or direct stimulation.1 The process is dependent on the correct balance of vasoactive substances, neurotransmitters, endocrine factors, and tissue fibroelastic properties.2 The vascular reaction is achieved by increased blood flow in the paired corpora and decreased outflow that leads to increased intracavernosal pressure and volume.3
Nitric oxide (NO) is the major mediator of smooth muscle relaxation in the cavernosal arteries and trabecular muscle that leads to an increase in cyclic guanosine monophosphate (cGMP) levels, which is ultimately degraded by phosphodiesterase-5 (PDE-5).4 Sexual desire may precede and encourage sexual activity, or it may be in response to sexual stimulation, with the downstream effects described. Those who have the desire to engage in sexual acts are more likely to be distressed when there is impairment in erectile function and pursue treatment.
Erectile dysfunction (ED) occurs when a man is unable to attain or maintain a sufficient erection for sexual intercourse.5 The International Index of Erectile Function (IIEF) is a standardized questionnaire that assesses a man’s ability to initiate, maintain, or complete sexual intercourse.6 Specifically, the IIEF-erectile function (IIEF-EF) domain includes six questions that evaluate the frequency and hardness of erections, penetration during intercourse, maintenance of an erection during intercourse, ability to maintain an erection to completion of intercourse, and a man’s confidence in their ability to get and maintain an erection to determine the severity of ED from mild to severe.6
The ED more commonly affects men of increasing age with *10% of men 20–30 years old and as many as 70% of men older than 70 years being diagnosed with ED.7–9 The etiology is related to aging and vascular, neurogenic, psychological, and hormonal components.10 Medications can also impact sexual functioning and erectile response. The pathogenesis, while multifactorial, has been linked to poor psychological status, arterial endothelial damage, and low testosterone.11,12
Hypogonadism is generally defined as low testosterone with symptoms and/or signs, including weakness, fatigue, decreased energy, low libido, reduced muscle and bone mass, and increased abdominal fat.13 In general, proposed cutoffs used to define hypogonadism are <300–400 ng/dL or <8–12 nmol/L.13 Based on varying definitions, the prevalence of hypogonadism in men with ED ranges from 1.7% to 35%.14–17 The American Urology Association (AUA) guidelines recommend the evaluation of testosterone in men with ED to determine whether hypogonadism could be influencing the disease process.18
The ED in patients with low testosterone may be due to low libido and/or changes in corpora cavernosa structure and function at the cellular level from hypogonadism.19 Hypogonadism can be associated with aging and medical conditions such as obesity, hyperlipidemia, metabolic syndrome, diabetes, hypertension, and coronary artery disease (CAD).1 Testosterone replacement therapy with or without PDE-5 inhibitors is an option to restore testosterone to normal levels and improve erectile function.
Testosterone and Sexual Function
-Animal studies
-Human studies
-Special populations
-Metabolic syndrome and type 2 diabetes
-Cardiovascular disease
Testosterone Replacement
-Testosterone monotherapy
-Combination therapy with testosterone replacement and PDE-5 inhibitors
-Special population considerations
-Management
-Treatment initiation. Although patients may exhibit
-Formulation selection
-Alternatives
-Monitoring
-Limitations: Complications and side effects
Conclusion
Both animal and human studies support an association between hypogonadism and ED. Animal studies first elucidated testosterone’s role in maintaining the proper synthesis and/or release of enzymes as well as tissue structure and function in the corpora cavernosa. When low testosterone is present in both animals and humans, erectile function is compromised as a result, which can be improved with testosterone replacement.
Testosterone monotherapy in hypogonadal men without significant comorbidities can improve erectile function in those struggling with ED. Combination therapy with testosterone and PDE-5 inhibitors can lead to improvement in erectile function for hypogonadal men with medical comorbidities who do not respond to monotherapy. Based on the evidence, it is important to screen all men with ED for hypogonadism, especially those with a history of inadequate response to PDE-5 inhibitors, so that the appropriate treatment plan is implemented. Further studies are crucial to better understand the nuances of testosterone treatment for patients with different degrees of hypogonadism and to optimize sexual outcomes in hypogonadal men with ED.
