Erectile dysfunction (ED) is a prevalent condition affecting millions of men worldwide, characterized by the inability to achieve or maintain an erection sufficient for sexual intercourse. While ED is often attributed to psychological factors, emerging evidence suggests a significant association with physiological conditions, including insulin resistance (IR).

IR, a hallmark of type 2 diabetes mellitus (T2DM) and metabolic syndrome, is a state in which cells become less responsive to insulin’s effects, leading to impaired glucose uptake and dysregulation of glucose metabolism. Beyond its well-established role in diabetes, IR has been implicated in various systemic complications, including cardiovascular disease, hypertension, and now, erectile dysfunction.

Urologist should consider evaluating insulin resistance in men presenting with erectile dysfunction, and comprehensive management strategies targeting both metabolic and sexual health parameters are warranted to optimize patient outcomes.

What is “insulin resistance”?

Insulin resistance is a physiological condition in which cells in the body become less responsive to the effects of insulin, a hormone produced by the pancreas. Insulin plays a crucial role in regulating blood sugar levels by facilitating the uptake of glucose from the bloodstream into cells, where it can be used for energy or stored for future use.

In individuals with IR, cells become less sensitive to the action of insulin, resulting in reduced glucose uptake. As a consequence, the pancreas compensates by producing more insulin to maintain normal blood sugar levels. This leads to elevated insulin levels in the bloodstream, a condition known as hyperinsulinemia.

IR is closely associated with various metabolic disorders, including type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome. It is also linked to other health conditions such as cardiovascular disease, hypertension, non-alcoholic fatty liver disease and erectgile dysfunction.

Calculation and normal values of insuline resistance

IR can be estimated using various methods, including mathematical models and laboratory tests. One commonly used method is the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), which provides an estimate of insulin sensitivity based on fasting insulin and glucose levels. Here’s how to calculate HOMA-IR:

Fasting Insulin Level: Measure the fasting insulin level in units of mIU/L (milli-international units per liter).

Fasting Glucose Level: Measure the fasting glucose level in units of mmol/L (millimoles per liter) or mg/dL (milligrams per deciliter).

Once you have these values, you can use the following formula to calculate HOMA-IR:

HOMA-IR = (Fasting Insulin (mIU/L) × Fasting Glucose (mmol/L)) / 22.5

Alternatively, if fasting glucose is measured in mg/dL, you can use the following formula:

HOMA-IR = (Fasting Insulin (mIU/L) × Fasting Glucose (mg/dL)) / 405

The resulting value represents an estimate of insulin resistance, with higher HOMA-IR values indicating greater insulin resistance.

Generally accepted ranges for HOMA-IR interpretation are as follows:

Low Insulin Resistance: HOMA-IR less than 1.0

Moderate Insulin Resistance: HOMA-IR between 1.0 and 2.9

High Insulin Resistance: HOMA-IR greater than or equal to 3.0

Diagnosis

Diagnosing IR typically involves a combination of clinical evaluation, laboratory tests, and assessment of risk factors. While there isn’t a single definitive test for insulin resistance, healthcare providers may utilize various methods to evaluate insulin sensitivity and assess the likelihood of insulin resistance. Here are some common diagnostic approaches:

Medical History and Physical Examination: Urologist will often begin by taking a detailed medical history, including assessing risk factors such as family history of diabetes, obesity, sedentary lifestyle, and presence of other metabolic conditions. A physical examination may also be conducted to evaluate signs such as central obesity (excess fat around the abdomen), acanthosis nigricans (darkened patches of skin), and signs of metabolic syndrome.

Blood Tests: Laboratory tests are crucial for assessing insulin sensitivity and related parameters. These may include:

• Fasting Plasma Glucose (FPG): Measures the concentration of glucose in the blood after an overnight fast. Elevated fasting glucose levels may indicate impaired fasting glucose or diabetes.
  • Oral Glucose Tolerance Test (OGTT): Involves drinking a glucose solution, followed by multiple blood glucose measurements over several hours to assess how the body processes glucose. This test can detect impaired glucose tolerance, a precursor to diabetes.
  • Hemoglobin A1c (HbA1c): Reflects average blood glucose levels over the past 2-3 months and is used to diagnose and monitor diabetes. Elevated HbA1c levels suggest poor glycemic control.
  • Fasting Insulin Levels: Measures the concentration of insulin in the blood after an overnight fast. Elevated fasting insulin levels may indicate insulin resistance.
  • Homeostatic Model Assessment of Insulin Resistance (HOMA-IR): Calculated from fasting insulin and glucose levels to estimate insulin resistance. A higher HOMA-IR value suggests greater insulin resistance.

Other Tests: Additional tests may be ordered to assess associated metabolic abnormalities and complications, such as lipid profile (cholesterol and triglycerides), liver function tests, and markers of inflammation.

Imaging Studies: In some cases, imaging studies such as ultrasound or MRI may be used to evaluate visceral adiposity (fat around internal organs), which is strongly associated with insulin resistance and metabolic syndrome.

Clinical Assessment Tools: Various clinical scoring systems and risk assessment tools, such as the Metabolic Syndrome Criteria or the Framingham Risk Score, may be used to evaluate overall cardiometabolic risk and likelihood of insulin resistance.

Symptoms

IR often develops gradually and may not cause noticeable symptoms in the early stages. However, as the condition progresses, individuals may experience a range of symptoms related to metabolic dysfunction and associated health issues. Some common symptoms and signs of insulin resistance include:

Weight Gain or Difficulty Losing Weight: Insulin resistance can lead to difficulty in maintaining a healthy weight or losing excess body fat, especially around the abdomen (central obesity). This is often accompanied by an increase in body mass index (BMI) and waist circumference.

Fatigue and Low Energy Levels: Fluctuations in blood sugar levels due to insulin resistance can result in feelings of fatigue, lethargy, and reduced energy levels throughout the day.

Increased Hunger and Food Cravings: Insulin resistance can disrupt the body’s ability to regulate appetite and satiety hormones, leading to increased hunger, particularly for sugary and high-carbohydrate foods.

Frequent Urination: Elevated blood sugar levels can lead to increased urine production, resulting in more frequent urination (polyuria), especially during the night.

Increased Thirst: Excessive urination can cause dehydration, leading to increased thirst (polydipsia) as the body attempts to maintain fluid balance.

Blurry Vision: Fluctuations in blood sugar levels can affect the shape of the lens in the eye, leading to temporary changes in vision, such as blurry vision or difficulty focusing.

Skin Changes: Insulin resistance is associated with skin conditions such as acanthosis nigricans, characterized by darkened, thickened patches of skin, typically in the folds and creases of the body (e.g., neck, armpits, groin).

Poor Wound Healing: High blood sugar levels can impair circulation and slow down the body’s ability to heal wounds and injuries, leading to delayed wound healing and increased susceptibility to infections.

Hormonal Imbalances: Insulin resistance can disrupt hormone levels in the body, leading to irregular menstrual cycles in women, decreased libido, and erectile dysfunction in men, and other hormonal imbalances.

Increased Risk of Cardiovascular Disease: IR is a significant risk factor for cardiovascular disease, including hypertension, dyslipidemia (elevated cholesterol and triglycerides), and atherosclerosis (hardening of the arteries).

It’s important to note that not everyone with insulin resistance will experience all of these symptoms, and some individuals may remain asymptomatic for an extended period.

Does insulin resistance cause erectile dysfunction?

Yes, IR can contribute to ED. The relationship between insulin resistance and ED is multifaceted and involves various physiological mechanisms. Here’s how insulin resistance can impact erectile function:

• Endothelial Dysfunction: IR is associated with ED, a condition characterized by impaired function of the cells lining the blood vessels. Endothelial dysfunction leads to reduced production of nitric oxide, a key signaling molecule that helps relax blood vessels and increase blood flow, including to the penis during sexual arousal. Insufficient nitric oxide availability can impair the ability to achieve and maintain an erection.
• Impaired Penile Blood Flow: Insulin resistance contributes to vascular abnormalities, including atherosclerosis (hardening and narrowing of arteries), which can restrict blood flow to the penis. Reduced blood flow to the penile arteries hinders the ability to achieve and sustain an erection.
• Hormonal Imbalances: IR is often associated with alterations in hormone levels, including decreased testosterone and increased estrogen. Testosterone is essential for normal libido and erectile function in men. Reduced testosterone levels, commonly seen in individuals with insulin resistance, can contribute to decreased sexual desire and difficulty achieving or maintaining erections.
• Neurological Factors: Insulin resistance may also affect the nervous system, including the nerves that control penile sensation and erectile function. Damage to these nerves, known as peripheral neuropathy, can impair the ability to achieve and sustain erections.
• Inflammation and Oxidative Stress: Insulin resistance is associated with chronic inflammation and increased oxidative stress in the body. These factors can contribute to damage to the blood vessels and nerves involved in erectile function, further exacerbating ED.
• Reduced Nitric Oxide Bioavailability: IR is associated with decreased bioavailability of nitric oxide due to increased oxidative stress and inflammation. Oxidative stress reduces the production of nitric oxide and promotes the formation of reactive oxygen species (ROS), which can further impair endothelial function and nitric oxide signaling in the penis, contributing to ED.
• Vascular Abnormalities: Insulin resistance is often accompanied by dyslipidemia (elevated levels of triglycerides and LDL cholesterol) and atherosclerosis (hardening and narrowing of arteries). These vascular abnormalities restrict blood flow to the penis, impeding the ability to achieve and maintain an erection. Additionally, insulin resistance-induced hyperinsulinemia can promote smooth muscle cell proliferation and vascular remodeling, further compromising penile blood flow and erectile function.
• Increased advanced glycation end-products (AGEs) and penile fibrosis: Insulin resistance contributes to the accumulation of AGEs, which are associated with tissue damage and fibrosis in various organs, including the penis. AGEs promote collagen cross-linking and fibrosis within the corpora cavernosa, leading to structural changes that impair erectile function.

Risk factors for IR induced ED

Several risk factors contribute to the development of ED induced by IR. These risk factors can increase the likelihood of both insulin resistance and ED, and their interplay exacerbates the condition. Here are some key risk factors:

• Obesity: Excess body weight, especially visceral adiposity (fat around the abdomen), is strongly associated with insulin resistance and metabolic dysfunction. Obesity contributes to chronic inflammation, hormonal imbalances, and vascular abnormalities, all of which can impair erectile function.
• Sedentary Lifestyle: Lack of physical activity and a sedentary lifestyle are significant risk factors for insulin resistance and obesity. Regular exercise helps improve insulin sensitivity, promote weight loss, and enhance cardiovascular health, all of which are essential for erectile function.
• Unhealthy Diet: Consuming a diet high in refined carbohydrates, sugars, and saturated fats can contribute to insulin resistance, dyslipidemia, and obesity. A poor diet also increases inflammation and oxidative stress, further exacerbating metabolic dysfunction and ED.
• Diabetes: Insulin resistance is a precursor to type 2 diabetes mellitus (T2DM), and individuals with diabetes are at increased risk of developing ED. Chronic hyperglycemia, vascular damage, neuropathy, and hormonal imbalances associated with diabetes can all contribute to ED.
• Hypertension: High blood pressure is closely linked to insulin resistance and endothelial dysfunction, both of which are implicated in ED. Hypertension contributes to vascular damage and reduced blood flow to the penis, impairing erectile function.
• Dyslipidemia: Elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol and decreased levels of high-density lipoprotein (HDL) cholesterol are common in individuals with insulin resistance. Dyslipidemia promotes atherosclerosis and vascular dysfunction, contributing to ED.
• Metabolic Syndrome: Metabolic syndrome is a cluster of metabolic abnormalities, including abdominal obesity, dyslipidemia, hypertension, and impaired glucose metabolism. Insulin resistance is a central feature of metabolic syndrome, and individuals with this condition are at increased risk of developing ED.
• Family History: Genetic factors play a significant role in the development of insulin resistance and metabolic disorders. Individuals with a family history of diabetes, obesity, or cardiovascular disease may have a higher predisposition to insulin resistance-induced ED.
• Age: Aging is associated with an increased prevalence of IR, vascular dysfunction, and hormonal changes, all of which contribute to ED. However, age-related changes alone may not fully account for the development of ED, especially when other risk factors are present.
• Smoking and Alcohol Use: Smoking, excessive alcohol consumption, and substance abuse are associated with insulin resistance, endothelial dysfunction, and vascular damage, all of which can contribute to ED.

Diagnosis

Diagnosing ED induced by IR involves a comprehensive evaluation by a Urologist, including assessing both metabolic and sexual health parameters. While there isn’t a specific test for ED induced by insulin resistance, the diagnosis typically involves a combination of medical history, physical examination, laboratory tests, and possibly specialized assessments. Here’s an overview of the diagnostic process:

Medical History: Urologist will conduct a detailed medical history, including asking about symptoms of ED, risk factors for insulin resistance (such as obesity, sedentary lifestyle, family history of diabetes), and any underlying medical conditions (such as diabetes, hypertension, or cardiovascular disease) that may contribute to both insulin resistance and ED.

Sexual History: A thorough sexual history is essential to evaluate the nature and severity of ED symptoms, including the frequency and quality of erections, presence of morning erections, and any factors that may exacerbate or alleviate ED symptoms.

Physical Examination: A physical examination may be performed to assess for signs of insulin resistance (such as central obesity, acanthosis nigricans) and other related conditions. Urologist may also evaluate for any anatomical abnormalities or signs of vascular disease that could contribute to ED.

Laboratory Tests: Laboratory tests may be ordered to assess metabolic parameters and hormonal levels that could contribute to insulin resistance and ED. These may include:

• Fasting blood glucose or hemoglobin A1c (HbA1c) to evaluate for diabetes or impaired glucose tolerance.
  • Fasting insulin levels or calculation of homeostatic model assessment of insulin resistance (HOMA-IR) to assess insulin sensitivity.
  • Lipid profile to evaluate for dyslipidemia.
  • Testosterone levels to assess for hormonal imbalances that may contribute to ED.
  • Other hormonal tests, such as prolactin and thyroid function tests, if indicated based on clinical suspicion.

Specialized Assessments: In some cases, specialized assessments may be recommended to further evaluate erectile function and vascular health. These may include:

• Erectile function questionnaire or self-administered validated questionnaires, such as the International Index of Erectile Function (IIEF), to assess the severity and impact of ED symptoms.
  • Nocturnal penile tumescence (NPT) testing to evaluate spontaneous erections during sleep, which can provide insight into the physiological mechanisms underlying ED.
  • Penile Doppler ultrasound to assess penile blood flow and detect any vascular abnormalities or arterial insufficiency contributing to ED.

Collaboration with Specialists: Depending on the findings of the initial evaluation, collaboration with specialists such as endocrinologists, urologists, or sexual medicine specialists may be warranted for further assessment and management of insulin resistance-induced ED.

Prevention of IR induced ED

Preventing ED induced by IR involves addressing both metabolic and sexual health aspects through lifestyle modifications and proactive management of risk factors. Here are some key strategies for preventing insulin resistance-induced ED:

• Maintain a Healthy Weight: Adopt a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats, while limiting refined carbohydrates, sugars, and saturated fats. Aim to achieve and maintain a healthy weight through calorie control and regular physical activity.
• Regular Exercise: Engage in regular aerobic exercise, resistance training, and flexibility exercises to improve insulin sensitivity, promote weight loss, and enhance cardiovascular health. Aim for at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity activity per week, along with muscle-strengthening activities on two or more days per week.
• Monitor Blood Glucose Levels: Individuals at risk of insulin resistance, such as those with obesity, family history of diabetes, or metabolic syndrome, should monitor their blood glucose levels regularly and work with urologists to optimize glycemic control.
• Healthy Lifestyle Habits: Avoid smoking, limit alcohol consumption, and avoid recreational drug use, as these behaviors can contribute to insulin resistance, endothelial dysfunction, and vascular damage, increasing the risk of ED.
• Manage Stress: Practice stress management techniques such as deep breathing exercises, meditation, yoga, and progressive muscle relaxation to reduce stress levels and improve overall well-being. Chronic stress can contribute to hormonal imbalances and exacerbate insulin resistance and ED.
• Regular Medical Check-ups: Schedule regular check-ups with healthcare providers to monitor blood pressure, lipid levels, and other metabolic parameters. Early detection and management of underlying medical conditions such as hypertension, dyslipidemia, and diabetes can help prevent ED and associated complications.
• Healthy Sleep Habits: Prioritize getting an adequate amount of quality sleep each night, aiming for 7-9 hours for most adults. Poor sleep quality and insufficient sleep duration are associated with insulin resistance, hormonal imbalances, and increased risk of ED.
• Address Mental Health Concerns: Seek professional help if experiencing symptoms of depression, anxiety, or other mental health issues, as these conditions can contribute to ED and impact overall sexual health.
• Open Communication: Maintain open and honest communication with your partner about sexual health concerns and seek support together if facing challenges related to ED. Couples counseling or sex therapy may be beneficial in addressing relationship issues and improving sexual intimacy.
• Medication Management: If prescribed medications that may contribute to ED (such as antihypertensives or antidepressants), discuss potential alternatives or adjustments with healthcare providers to minimize adverse effects on sexual function.

Treatment

The treatment of ED induced by insulin resistance involves addressing both the underlying metabolic dysfunction and the sexual health aspects. Here are various treatment approaches that may be considered:

Lifestyle Modifications:

• Healthy Diet: Adopting a balanced diet low in refined carbohydrates and sugars and rich in fruits, vegetables, whole grains, lean proteins, and healthy fats can help improve insulin sensitivity and overall metabolic health.
  • Regular Exercise: Engaging in regular physical activity, such as aerobic exercise and resistance training, can help improve insulin sensitivity, promote weight loss, and enhance cardiovascular health, all of which may positively impact erectile function.
  • Weight Loss: Achieving and maintaining a healthy weight can improve insulin sensitivity and reduce the risk of ED. Even modest weight loss can lead to significant improvements in metabolic parameters and sexual health.

Medications:

• Insulin Sensitizers: Medications such as metformin, thiazolidinediones (e.g., pioglitazone), and sodium-glucose cotransporter-2 (SGLT2) inhibitors (e.g., dapagliflozin, empagliflozin) may be prescribed to improve insulin sensitivity and glycemic control in individuals with IR and diabetes. These medications may indirectly improve erectile function by addressing underlying metabolic dysfunction.
  • Phosphodiesterase-5 (PDE5) Inhibitors: Medications such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) are commonly used to treat ED by enhancing the effects of nitric oxide, thereby increasing penile blood flow and facilitating erections. PDE5 inhibitors may be effective in individuals with insulin resistance-induced ED, although they may be less effective in cases of severe vascular impairment.

Hormonal Therapy:

• Testosterone Replacement Therapy: In cases of testosterone deficiency associated with insulin resistance, testosterone replacement therapy may be considered to restore testosterone levels to the normal range and improve libido and erectile function. Testosterone therapy should be prescribed and monitored by a qualified healthcare provider, as it carries potential risks and side effects.

Psychosexual Therapy:

• Counseling and Behavioral Interventions: Psychosexual therapy, including cognitive-behavioral therapy (CBT), sex therapy, and couples counseling, may be beneficial for individuals with insulin resistance-induced ED, particularly when psychological factors such as performance anxiety or relationship issues contribute to sexual dysfunction.

Treatment of Underlying Conditions:

• Management of Comorbidities: Optimizing the management of underlying conditions associated with insulin resistance, such as diabetes, hypertension, dyslipidemia, and cardiovascular disease, is essential for improving overall metabolic health and reducing the risk of ED.

Invasive Treatments:

• Penile Prostheses: In cases of severe and refractory ED, surgical placement of penile prostheses may be considered as a last resort option to restore erectile function.

It’s important for individuals experiencing ED related to insulin resistance to consult with a Urologist for a comprehensive evaluation and personalized treatment plan. Treatment strategies should address both metabolic and sexual health aspects to optimize outcomes and improve overall quality of life.

Summary

The connection between insulin resistance and ED stems from multiple mechanisms, including endothelial dysfunction, hormonal imbalances, neurological factors, inflammation, and vascular abnormalities. Insulin resistance contributes to endothelial dysfunction, reducing nitric oxide-mediated vasodilation and impairing penile blood flow regulation. Hormonal imbalances, such as decreased testosterone and increased estrogen, further exacerbate erectile dysfunction. Neurological dysfunction and chronic inflammation also play significant roles.

Recognizing the relationship between insulin resistance and erectile dysfunction has profound clinical implications. ED may serve as an early clinical marker of underlying metabolic disturbances, providing an opportunity for early intervention and prevention of more serious complications. Understanding these mechanisms can guide diagnostic considerations and therapeutic interventions, emphasizing holistic approaches to men’s health that integrate metabolic and sexual health paradigms.

Overall, elucidating the connection between insulin resistance and erectile dysfunction underscores the importance of addressing metabolic health in the management of sexual dysfunction. By adopting comprehensive strategies that target both metabolic and sexual health parameters, clinicians can optimize patient care and improve outcomes for individuals affected by insulin resistance-induced erectile dysfunction.

Prof. Dr. Emin ÖZBEK

Urologist

Istanbul- TURKEY