Erectile dysfunction

Epidemiology of Erectile Dysfunction (ED)

Prevalence:
- Approximately 52% of men in the US aged 40-70 years have ED.
- Estimated 30-50 million men in the US and at least 150 million men globally have ED.
- Projected to affect 322 million men worldwide by 2025.
- Underreporting due to embarrassment, cultural factors, and lack of physician inquiry may lead to underestimation.
Age-related Prevalence:
- At age 40, about 40% of men are affected by ED.
- At age 70, about 70% of men report having ED.
Co-morbidities:
- Higher prevalence in men with diabetes, hypogonadism, and cardiovascular disease.

Pathophysiology of Erectile Dysfunction (ED)

Erection Mechanism:
- Relaxation of Intracavernosal Smooth Muscle:
  - Increases blood flow into the corpora cavernosa.
  - Compresses emissary veins, reducing venous outflow.
Neural Control:
- Controlled by paraventricular and medial preoptic nuclei of the hypothalamus.
- Signals travel through the parasympathetic nervous system to the S2-S4 sacral plexus.
- Cavernosal nerves release nitric oxide to initiate erection.
Role of Nitric Oxide (NO):
- NO released by cavernous nerve terminals and endothelial cells.
- Stimulates cyclic guanosine monophosphate (GMP) production in smooth muscle.
- Cyclic GMP activates protein kinase G:
  - Opens potassium channels.
  - Closes calcium channels.
- Low intracellular calcium causes smooth muscle relaxation, increasing arterial flow and reducing venous outflow.
Maintenance of Erection:
- Increased blood flow and veno-occlusive activity result in rigid erection with minimal blood flow out of the corpora.
- Penile phosphodiesterase degrades cyclic GMP, causing corporal smooth muscle contraction and erection reversal.
Dysfunction Causes:
- Any disruption in the neural control, NO production, cyclic GMP activity, or veno-occlusive mechanism can result in ED.

Aetiological factors are multimodal

biological
psychological
sociocultural
relational
sexual

Multifactorial Causes

Psychological Causes:
- Depression
- Stress
- generalised anxiety disorder
- Performance anxiety
- Other disorders
  - self-image problems
  - low self-esteem
  - partner-related
  - history of sexual abuse
  - highly restricted sexual upbringing
Organic Causes:
- Aging
- Cardiovascular diseases
- Hypertension
- Diabetes mellitus
- Metabolic syndrome
- Neurological diseases (e.g., multiple sclerosis)
  - Alzheimer’s disease
  - multiple sclerosis
  - Parkinson’s disease
  - Stroke
  - spinal cord injuries
  - peripheral nerve disorders (diabetic neuropathy)
- Hormonal causes
  - Hypogonadism
  - Hyperprolactinaemia
  - thyroid disorder
- Trauma (e.g., pelvic fractures, spinal cord injuries)
- Hyperlipidemia
- Stroke
- Sleep apnea
- Chronic Obstructive Pulmonary Disease (COPD)
- Glaucoma
- Penile abnormalities
  - Peyronie’s disease
  - venous leak
  - Sequelae of priapism
- Benign Prostatic Hyperplasia (BPH) with Lower Urinary Tract Symptoms (LUTS)
- Iatrogenic causes (e.g., post-transurethral resection of the prostate)
- Medications (e.g., antidepressants, antihypertensives, antipsychotics, opioids, recreational drugs)

Cardiovascular Disease and Erectile Dysfunction

Significant Risk Factor:
- Almost 50% of men with known coronary artery disease have significant ED.
- ED can precede coronary artery disease by up to 5 years due to smaller cavernosal arteries developing blockages earlier.
- ED is a significant indicator of underlying heart disease.
Screening and Referrals:
- Screen all patients with ED for cardiovascular risks.
- Perform non-invasive testing for subclinical atherosclerosis and exercise stress tests for intermediate risk.
- Recommend a formal cardiology referral for high-risk patients.

Correlations with Other Conditions

Hypertension:
- About 40% of men with ED have hypertension.
- 35% of hypertensive men also have ED.
Hyperlipidemia:
- Present in about 42% of men with ED.
Diabetes Mellitus:
- Undiagnosed diabetes is more likely in men with ED (28% vs. 10% in non-diabetic men with normal erections).
- Men over 50 with diabetes are roughly twice as likely to have ED (46% vs. 24% in non-diabetics).
Hypogonadism:
- One-third of diabetic men with ED have hypogonadism.
- Up to 35% of all men with ED have hypogonadism.
- About 6% have abnormal thyroid function.
Obesity:
- Associated with a 50% increase in ED.
- One-third of obese men with ED who enrolled in a weight loss program resolved their ED symptoms in 2 years.
Smoking:
- Quitting smoking improves erectile quality by 25% after one year.
Alcohol Use:
- Heavy alcohol use is associated with an increased risk of ED.
Benign Prostatic Hyperplasia (BPH) with LUTS:
- Up to 72% of men with symptomatic BPH also have ED.
Depression:
- Patients with depression are almost 40% more likely to have ED.
- The incidence of depression in men with ED is almost three times greater.
Premature Ejaculation:
- At least 30% (up to 60%) of patients with ED also have premature ejaculation.
Medications:
- Prescription medications cause about one-quarter of all ED cases.
- Most common medications associated with ED
  - antihypertensives (e.g. diuretics, alpha and beta blockers)
  - antidepressants – selective serotonin reuptake inhibitors and other antidepressants
  - psychotropics
    - antipsychotics
    - anxiolytics
  - anticonvulsants, anti-Parkinson’s drugs
  - hormone-affecting drugs – antiandrogens, corticosteroids, chronic opioid use
Prostate Cancer Treatments:
- Radical prostatectomy surgery: 85% post-operative ED rate.
- Radiation therapy: 25% post-operative ED rate.
- Robotic surgery for radical prostatectomies has not changed the post-operative incidence of ED.
Bicycle Riding:
- Controversial, but traditional racing bicycle seats can cause pressure on the perineal nerves and arteries.
- A 2020 meta-analysis indicated an increased risk of ED in cyclists compared to non-cycling controls.

History

General Health: Chronic illnesses (e.g., diabetes, hypertension), cardiovascular history.
Medication List: Include all prescription medications, over-the-counter drugs, and supplements.
Lifestyle Factors: Smoking, alcohol use, recreational drug use, activity level.
Vascular Risk Factors: Hypertension, hyperlipidemia, diabetes.
Psychosocial History: Stress, anxiety, depression, relationship status.

Key Questions in the Assessment of Erectile Dysfunction

Define Sexual Function

Age at Onset and Duration
- Younger Onset:
  - Aspect: Points towards psychological causes or acute events.
  - Differentiation: Requires evaluation of recent stressors, relationships, and mental health.
- Older Onset:
  - Aspect: Linked to chronic health conditions.
  - Differentiation: Screening for cardiovascular disease, diabetes, age-related hormonal changes.

Duration of the Erection

Importance: Determines whether the issue is achieving or maintaining an erection.
- Aspect: Identifies primary problem area.
- Differentiation: Achieving erection (arterial issues) vs. maintaining erection (venous leak or anxiety).

Numbness or Unusual Sensations in the Penis

Importance: Indicates possible neurological issues or peripheral neuropathy.
- Aspect: Neurological health.
- Differentiation: Neurological vs. vascular or psychological causes.

Loss of Rigidity During Foreplay or Penetration

Importance: Helps differentiate between psychological and physiological causes.
- Aspect: Timing and context of rigidity loss.
- Differentiation: Psychological (foreplay) vs. structural or vascular issues (penetration).

Consistency of Morning and Overnight Erections

Importance: Morning erections typically indicate intact physiological mechanisms.
- Aspect: Physiological health.
- Differentiation: Psychological (if present during morning) vs. organic (if absent).

Variability in Erection Hardness Day-to-Day

Importance: Fluctuations can point to psychological factors, hormonal imbalances, or varying health conditions.
- Aspect: Consistency and reliability.
- Differentiation: Psychological vs. hormonal or health condition fluctuations.

Comparison of Erection Quality During Masturbation vs. Intercourse

Importance: Better erections during masturbation may indicate performance anxiety or relationship issues.
- Aspect: Contextual performance.
- Differentiation: Psychological (better during masturbation) vs. consistent organic issues.

Quality of Erections

Evaluates Severity:
- Describing erection quality (0-100%) helps in quantifying severity.
- Differentiation: Psychological factors (better quality in certain situations) vs. organic causes (consistently poor quality).

Frequency of Dysfunction

Occasional Dysfunction:
- Aspect: Transient stress or situational anxiety.
- Differentiation: Psychological causes.
Frequent or Constant Dysfunction:
- Aspect: Chronic physical conditions.
- Differentiation: Organic causes.

Social issues

Relationships, Life Stressors
- Differentiation: Psychological stress vs. organic causes exacerbated by stress, Life changes can significantly impact sexual function.
Quality and Quantity of Sleep, Snoring and Sleep Apnea, Weight, Exercise, Alcohol, Smoking History
- Modifiable lifestyle factors vs. underlying chronic health issues.

Examination

Secondary sexual characteristics
BMI
Penile plaque/ deformity
- Hypospadias
- Phimosis
- Peyronie’s disease
- evidence of hypogonadism
Teste size, masses
CV – BP
signs of PVD
- Abdominal or femoral artery bruits
- lower extremity pulses
neurological
- superficial anal reflex
  - assessed by touching the perianal skin and noting contraction of the external anal sphincter muscles.
  - indicative of normal somatic function of sacral cord levels S2–4
- bulbocavernosus reflex
  - performed by placing a finger in the rectum and noting contraction of the anal sphincter and bulbocavernosus muscle when the glans penis is squeezed
  - demonstrates normal sacral cord function.
  - External anal sphincter tone can be assessed during this maneuver as well.

Investigations

Workup CV risk – blood sugars, lipid profile
Consider hormone levels – testosterone, LH, prolactin
- Controversial if young and healthy without hypogonadal symptoms
- May be warranted if suspicious taking supplements
Penile colour duplex ultrasonography
- if history of trauma or abnormal physical exam
- done with cavernosal injection to maintain

Likely Causes of Erectile Dysfunction Based on Clinical Presentation

Psychologic causes
- Young age with abrupt onset
- Onset associated with specific emotional event
- Dysfunction in certain settings while normal function in others
- Persistence of nocturnal erections
- Previous history of erectile dysfunction with spontaneous improvement
- Excessive life stressors—work, relationships
- Mental status findings suggestive of depression, psychosis or anxiety disorder
Organic causes
- Vasculogenic—arterial
  - Persistent interest in sex
  - Older age with gradual onset
  - Impaired function in all settings
  - Presence of chronic disease (particularly diabetes, hypertension)
  - Use of prescription/over-the-counter medications associated with erectile dysfunction
  - Smoking
  - Elevated blood pressure, evidence of peripheral vascular disease (bruits, decreased pulses, skin and hair changes consistent with arterial insufficiency)
Vasculogenic—venous
- Inability to maintain erection once established
- Prior history of priapism
- Local anomalies of the penis
Neurogenic
- History of spinal cord/pelvic trauma or surgery
- Presence of chronic disease (diabetes, alcoholism)
- Presence of neurologic condition (multiple sclerosis, stroke)
- Abnormal neurologic examination of genitals/perineum
Hormonal
- Loss of interest in sexual activity
- Small atrophic testis
- Low testosterone, elevated prolactin
  - Testosterone replacement may increase libido without improving erectile function
  - Before the initiation of testosterone therapy, the patient should be evaluated for the possibility of an occult prostate malignancy, which may be stimulated by supplemental testosterone

Treatment

General Considerations

Vasculogenic or Neurogenic Causes: Trial of therapy in primary care.
Psychogenic Etiology: Sexual counseling or psychiatric referral.
All Other Patients: Reasonable to initiate treatment regardless of etiology.

Address Lifestyle Factors

Smoking Cessation
Reduce Alcohol Intake
Increase Physical Activity
Healthy Diet

Psychological Interventions

Sexual Counseling: For psychogenic ED.
Psychiatric Referral: For underlying mental health issues (e.g., anxiety, depression).
Validation: Acknowledge and validate the patient’s concerns to alleviate psychological distress.

Pharmacological Interventions:

PDE5 Inhibitors

Common Medications:
- Sildenafil: 25, 50, 100 mg
- Vardenafil: 5, 20 mg
- Avanafil: 50, 100, 200 mg
- Tadalafil: 5, 10, 20 mg
Key Points:
- Mechanism: Effective with sexual arousal (release of NO).
- Misconceptions: Not aphrodisiacs; educate patients and partners.
- Response Variability: May need to try at least 2 different types.
- Dosing: Start on medium to high dose; can be halved if needed.
- Timing: Take 1–2 hours before intercourse.
- Daily Dosing: Beneficial for ED with benign prostatic hyperplasia (BPH).
- Trial Period: Try on a few different occasions, initially alone to reduce performance pressure.
- Non-Responders: Consider second-line therapy if no response to two different PDE5 inhibitors.
Contraindications: Do not combine with nitrates.
- Nitrate Medications:
  - Risk: Severe hypotension.
  - Examples: Nitroglycerin, isosorbide dinitrate.
- Alpha-Blockers:
  - Risk: Hypotension.
  - Management: Careful timing and monitoring when used together.
- Severe Cardiovascular Conditions:
  - Risk: Increased risk of cardiac events.
  - Examples: Recent myocardial infarction, severe heart failure, unstable angina.
Severe Liver or Kidney Disease:
- Risk: Impaired metabolism and excretion leading to increased drug levels and toxicity.
Adverse Effects:
- Headaches
- facial flushing
- indigestion – Use of antacids or H2 blockers, avoiding large meals before medication.
- nasal congestion
- dizziness
- visual disturbances – Typically transient; reducing the dose or switching to a different PDE-5 inhibitor may help.
- myalgia.
serious side effects
- Hypotension:
  - Risk: Especially significant when combined with nitrates or alpha-blockers.
  - Mechanism: Profound vasodilation can lead to dangerously low blood pressure.
- Priapism:
  - Risk: Rare but serious.
  - Mechanism: Prolonged erection lasting more than 4 hours can cause permanent damage.
  - Management: Requires immediate medical attention, typically treated with intracavernosal injections of diluted phenylephrine or surgical intervention.
- Sudden Hearing Loss:
  - Risk: Rare.
  - Mechanism: Exact cause unknown, but may involve changes in blood flow to the inner ear.
  - Symptoms: Rapid onset of hearing loss, often unilateral.
- Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION):
  - Risk: Rare.
  - Mechanism: Reduced blood flow to the optic nerve.
  - Symptoms: Sudden vision loss in one eye.
- Cardiovascular Events:
  - Risk: Increased in patients with pre-existing cardiovascular conditions.
  - Mechanism: Increased physical exertion during sexual activity can trigger events in susceptible individuals.
  - Precaution: Thorough cardiovascular assessment before initiating therapy in high-risk patients.

Non-Pharmacological Interventions

External Vacuum Devices:
- Mechanism: Creates an erection by engorging the penis with blood using a vacuum pump and maintaining it with an elastic band.
- Efficacy: High efficacy rates (70-80%), but lower patient satisfaction.
- Usage: Requires practice and manual dexterity.
- Advantages: Cost-effective, safe, suitable for frequent use.
Intraurethral Prostaglandin E1 Pellets (MUSE):
- Mechanism: Urethral suppositories that dissolve and induce erection by relaxing penile muscles.
- Efficacy: 50-65% success rate.
- Usage: High cost, variable efficacy, side effects include urethral burning.
Intracavernosal Injections:
- Medications: Prostaglandin E1 (most common), papaverine, phentolamine, atropine.
- Usage: High effectiveness (up to 94%), but painful and relatively expensive.
- Combination Therapy: TriMix (papaverine, phentolamine, prostaglandin E1) or QuadMix (adding atropine) offers better results.
- Adverse Effects: Pain, priapism, bleeding, scarring.
Penile Implants:
- Types:
  - Malleable Prosthesis: Manually adjustable.
  - Inflatable Prosthesis: Activated by a pump, offering a more natural function.
- Complications: Erosion, leakage, infection, mechanical failure.
- Satisfaction Rates: High patient satisfaction (about 90%); long-term usage decreases over time.
Penile Revascularization Surgery:
- Usage: Suitable for younger patients with isolated vascular injury post-trauma.
- Procedure: Anastomosis of inferior epigastric artery to the dorsal artery of the penis.
- Efficacy: Marginal long-term results.
Low-Intensity Shockwave Therapy:
- Mechanism: Improves hemodynamics, endothelial cell proliferation, and penile revascularization.
- Efficacy: Promising short-term results in mild to moderate ED; overall success rate around 40%.
- Usage: Investigational, not FDA-approved in the US.

Safe Sex Practices

Education: Discuss safe sex practices to prevent sexually transmitted infections (STIs).

Age-Related Psychological Considerations

Young Men (Early 20s):
- Focus: Emerging identity, body image, sexual identity.
- Contradictions: Strong-weak, mature-immature, independent-dependent, stoic-emotional, sexual predator-sexually vulnerable.
Mid 20s:
- Focus: Engagement with external environment (work) and personal relationships.
- Issues: Confusion, uncertainty, anxiety presenting as ED.
Middle-Aged Men:
- Focus: Loss of youth, emerging old age, disengagement from workforce.
- Concerns: Anxiety about aging, relationship dynamics, preoccupation with changing life roles.

Monitoring and Follow-Up

Regular Check-Ins: Monitor treatment effectiveness and adverse effects.
Lifestyle Modifications: Encourage ongoing healthy lifestyle changes.
Psychological Support: Provide continuous psychological support if needed.
Partner Involvement: Involve partner in treatment discussions and plans.

Testosterone Supplementation:
- Beneficial in severe hypogonadism and low libido, but not as effective for ED alone.
- Only 35% of hypogonadal patients with ED show significant improvement with testosterone supplementation.
Combined Therapy:
- Intracavernosal injections plus PDE-5 inhibitors can be effective but increase the risk of priapism.
- Synergistic effect but requires careful monitoring and limited experience.

Erectile Dysfunction (ED) and Low Libido

Erectile dysfunction (ED) and low libido often coexist, but they are distinct conditions with different underlying mechanisms and implications. Understanding their correlation is essential for accurate diagnosis and effective treatment.

Common Underlying Factors

Hormonal Imbalances:
- Testosterone: Low testosterone levels (hypogonadism) can lead to both ED and decreased libido.
  - ED: Testosterone is crucial for the maintenance of erectile function through its role in nitric oxide synthesis and penile tissue health.
  - Libido: Testosterone directly influences sexual desire and interest.
Psychological Factors:
- Stress, Anxiety, and Depression:
  - These mental health conditions can reduce sexual desire (libido) and impair the physiological processes necessary for achieving and maintaining an erection.
  - Performance anxiety specifically can lead to a cycle where anxiety about sexual performance causes ED, which in turn reduces sexual desire.
Chronic Illnesses:
- Diabetes, Cardiovascular Disease:
  - These conditions can impair blood flow and nerve function, leading to ED.
  - Chronic illness can also reduce overall energy levels and interest in sexual activity, contributing to low libido.
Medications:
- Antidepressants, Antihypertensives, and Others:
  - Certain medications can cause ED and low libido as side effects.
  - For example, selective serotonin reuptake inhibitors (SSRIs) are known to reduce sexual desire and cause erectile difficulties.
Aging:
- With aging, there is a natural decline in testosterone levels, which can lead to both ED and low libido.
- Older men often experience a decrease in overall physical health, contributing to both conditions.

Distinct but Interrelated

ED and Low Libido Can Occur Independently:
- ED without Low Libido: A man might have a strong desire for sex but be unable to achieve or maintain an erection due to vascular or neurological issues.
- Low Libido without ED: A man might not have the desire for sex but can achieve and maintain an erection when aroused.
Interplay and Feedback Loop:
- Psychological Impact: ED can lead to frustration, anxiety, and depression, which further reduces libido.
- Low Libido Impact: Low libido can reduce the frequency of sexual activity, leading to disuse atrophy of the penile tissues and vascular system, contributing to ED.

Clinical Implications

Beneficial in severe hypogonadism and low libido, but not as effective for ED alone.
Only 35% of hypogonadal patients with ED show significant improvement with testosterone supplementation.

Assessment:
- Thorough History: Determine if the patient is experiencing ED, low libido, or both. Explore symptoms, onset, duration, and associated factors.
- Hormonal Evaluation: Measure testosterone levels to identify hypogonadism.
- Psychological Evaluation: Assess for stress, anxiety, depression, and relationship issues.
Treatment:
- PDE-5 Inhibitors: Effective for ED but not for increasing libido.
- Testosterone Supplementation: Beneficial for men with hypogonadism and both ED and low libido.
- Psychological Counseling: Important for addressing psychogenic causes and improving overall sexual health.
- Lifestyle Modifications: Encourage healthy lifestyle changes to improve both conditions.

Erectile Dysfunction (ED) following prostate cancer

ED post prostatectomy 60%
May return in 6-18 months – neuropraxia settles
Radiation therapy and androgen deprivation therapy will worsen – often medically refractory
Often associated with loss in penile size – related to cavernosal hypoxia and fibrosis
Penile rehabilitation
- After radical prostatectomy, radiation
- Regular PDE5
- Consider injection/ vacuum if wanting to remain sexually active and preserve length
Consider co-existing urinary/bowel, psychological, relationship,