Adult-Onset Male Sexual Dysfunction: A Comprehensive Clinical Approach for the Internist

DR Neeraj Manikath , claude.ai

Abstract

Male sexual dysfunction (MSD) affects 40-50% of men over 40 years and represents a sentinel marker for systemic disease, particularly cardiovascular pathology. This review provides internists with a structured approach to evaluating adult-onset MSD, emphasizing its role as a window into overall health. We discuss pathophysiology, systematic evaluation, and evidence-based management strategies with practical clinical pearls for postgraduate trainees.

Introduction

Sexual dysfunction in men encompasses erectile dysfunction (ED), ejaculatory disorders, decreased libido, and orgasmic dysfunction. While often dismissed as a quality-of-life issue, adult-onset MSD frequently heralds significant systemic disease. The landmark observation that ED precedes coronary events by 3-5 years (the "artery size hypothesis") transforms sexual health assessment into cardiovascular risk stratification.

Pearl #1: ED is not just a urological problem—it's an internist's problem. Consider ED as "angina of the penis."

Epidemiology and Clinical Significance

The Massachusetts Male Aging Study demonstrated age-dependent prevalence: mild ED affects 17% of men at age 40, rising to 34% at age 70. Complete ED increases from 5% to 15% over the same period. More critically, the Princeton Consensus Panel established that men with ED have 1.5-2 fold increased risk of cardiovascular events, independent of traditional risk factors.

Oyster #2: When a patient presents with new-onset ED, you're not just treating sexual dysfunction—you're identifying a man at high cardiovascular risk who needs aggressive risk factor modification.

Pathophysiology: The Vascular-Endothelial-Neurogenic Triad

Erectile Mechanism

Normal erection requires:

Intact neurologic pathways (parasympathetic S2-S4)
Functional vascular supply (internal pudendal artery → penile arteries)
Healthy endothelium producing nitric oxide (NO)
Venous occlusion mechanism

The hemodynamics are remarkable: penile blood flow increases from 3-5 mL/min to 50-60 mL/min during erection—a 10-15 fold increase. This requires exquisite endothelial function.

The Endothelial Connection

Endothelial dysfunction represents the common pathway linking ED with cardiovascular disease, diabetes, and metabolic syndrome. NO bioavailability decreases due to:

Oxidative stress
Inflammation (elevated CRP, IL-6)
Advanced glycation end-products (in diabetes)
Decreased endothelial NO synthase (eNOS) activity

Clinical Hack #3: Order high-sensitivity CRP and hemoglobin A1c in every patient with new ED. You'll frequently uncover previously undiagnosed diabetes or inflammatory states.

Systematic Clinical Evaluation

History: The 5-Domain Assessment

1. Sexual History (IIEF-5 Questionnaire) The International Index of Erectile Function-5 is a validated 5-question tool (scores 5-25):

22-25: No ED
17-21: Mild ED
12-16: Mild-moderate ED
8-11: Moderate ED
5-7: Severe ED

2. Cardiovascular Risk Stratification

Hypertension (affects 40% of ED patients)
Diabetes (3-fold ED risk)
Dyslipidemia
Smoking history (2-fold risk)
Sedentary lifestyle

3. Medication Review High-risk medications:

Beta-blockers (particularly non-selective)
Thiazide diuretics
SSRIs/SNRIs (70% cause sexual dysfunction)
5-alpha reductase inhibitors
Spironolactone (anti-androgenic)
Opioids (hypogonadotropic hypogonadism)

Pearl #4: Before prescribing any new chronic medication, ask: "Could this affect sexual function?" Particularly important with antihypertensives and antidepressants.

4. Psychosocial Assessment Depression coexists in 40% of ED patients. The relationship is bidirectional—ED causes depression, and depression causes ED.

Screen with PHQ-9 or simple questions:

"Has this affected your mood or caused relationship stress?"
"Do you experience morning erections?" (suggests psychogenic component)

5. Endocrine Symptoms

Decreased libido (testosterone deficiency)
Gynecomastia (hyperprolactinemia, liver disease)
Hot flashes (severe hypogonadism)

Oyster #5: Isolated ED with preserved libido usually indicates vascular/organic cause. ED with decreased libido suggests hormonal etiology.

Physical Examination: Beyond the Obvious

Cardiovascular Assessment

Blood pressure (both arms)
Peripheral pulses (absent femoral pulses suggest Leriche syndrome)
Carotid bruits
Abdominal aortic pulsation

Endocrine Signs

Body habitus (central obesity → metabolic syndrome)
Gynecomastia
Testicular size/consistency (normal 15-25 mL; <15 mL suggests hypogonadism)
Secondary sexual characteristics

Neurological Examination

Perineal sensation (S2-S4 dermatomes)
Cremasteric reflex
Bulbocavernosus reflex (advanced assessment)

Clinical Hack #6: Check ankle brachial index (ABI) in ED patients over 50. Abnormal ABI (<0.9) dramatically increases cardiovascular event risk and mandates aggressive intervention.

Laboratory Investigation: The Targeted Approach

First-Tier Testing (All Patients)

Fasting glucose and HbA1c
- 35% of ED patients have undiagnosed diabetes
- Microvascular and macrovascular complications
Lipid profile
- Target LDL <70 mg/dL in high-risk patients
- Consider ED patients as cardiovascular equivalent
Morning total testosterone (8-10 AM)
- Repeat if <300 ng/dL
- Diurnal variation significant
TSH
- Both hypo- and hyperthyroidism affect erectile function

Pearl #7: Always obtain testosterone between 8-10 AM and repeat abnormal values. Single measurements are unreliable due to pulsatile secretion and circadian rhythm.

Second-Tier Testing (Selected Patients)

If testosterone <300 ng/dL:

Free testosterone (normal >50 pg/mL)
LH and FSH
Prolactin
SHBG

Interpretation patterns:

Low T + High LH/FSH = Primary hypogonadism
Low T + Low/Normal LH/FSH = Secondary hypogonadism
High prolactin (>25 ng/mL) → MRI pituitary

If refractory to treatment:

Nocturnal penile tumescence testing
Penile Doppler ultrasound
Consider referral for specialized testing

Oyster #8: Prolactinomas often present with ED and decreased libido before visual symptoms. Check prolactin in any patient with ED plus persistent headaches or visual changes.

The Vascular-Hormonal-Psychogenic Algorithm

Decision Tree Approach

Step 1: Morning Erections?

Present → Psychogenic component likely
Absent → Organic cause likely

Step 2: Onset Pattern

Acute onset → Psychogenic or medication-related
Gradual onset → Vascular/endocrine

Step 3: Libido Status

Normal libido + ED → Vascular cause
Decreased libido + ED → Hormonal cause

Step 4: Response to PDE5 Inhibitors

Good response → Proceed with treatment
Poor response → Investigate hormonal, neurogenic, or severe vascular disease

Clinical Hack #9: The "therapeutic trial" approach: In low-risk patients with likely vascular ED, try PDE5 inhibitors while investigations proceed. Response confirms diagnosis and improves patient engagement.

Evidence-Based Management

Lifestyle Modification: First-Line Intervention

Multiple studies demonstrate improvement with:

Weight loss: 30% improvement in erectile function with 10% body weight reduction
Exercise: 160 minutes/week moderate aerobic exercise improves ED
Smoking cessation: Improvement seen within 6-12 months
Alcohol reduction: >8 drinks/week associated with ED
Mediterranean diet: Improves endothelial function

Pearl #10: Prescribe lifestyle modification with the same intensity as medication. Say: "Exercise is as effective as medication for mild ED—I'm prescribing 30 minutes daily walking."

Pharmacotherapy

PDE5 Inhibitors: Mechanism and Selection

All PDE5 inhibitors enhance NO-mediated vasodilation by preventing cGMP breakdown.

Comparison:

Drug	Onset	Duration	Food Effect	Dose Range
Sildenafil	30-60 min	4-6 hours	High-fat delays	25-100 mg
Tadalafil	30-45 min	36 hours	Minimal	5-20 mg
Vardenafil	30-60 min	4-6 hours	High-fat delays	5-20 mg
Avanafil	15-30 min	6 hours	Minimal	50-200 mg

Clinical Hack #11: For patients wanting spontaneity, start with tadalafil 5 mg daily (also approved for BPH). For cost-conscious patients, generic sildenafil works excellently.

Contraindications:

Nitrate use (absolute)
Severe cardiovascular disease (NYHA III-IV)
Recent stroke/MI (<90 days)
Hypotension (<90/50)
Severe hepatic impairment

Oyster #12: The "2-strikes rule"—if a PDE5 inhibitor fails twice with proper dosing and timing, optimize dose or try alternative agent before declaring treatment failure. Many patients use incorrectly initially.

Testosterone Replacement

Indications:

Total testosterone <300 ng/dL (confirmed on repeat)
Symptoms of hypogonadism
No contraindications

Options:

Topical gel: 50-100 mg daily (physiologic)
IM injections: 200 mg q2 weeks
Subcutaneous: 75 mg weekly
Transdermal patch: 4-6 mg daily

Monitoring:

Testosterone levels at 3-6 months
Hematocrit (target <54%)
PSA (controversial but recommended)
Digital rectal exam annually >50 years

Pearl #13: Combination therapy (PDE5 inhibitor + testosterone) works synergistically in hypogonadal men. Testosterone alone improves libido; combined therapy improves erectile function.

Second-Line Therapies

Intraurethral alprostadil (MUSE):

60-65% efficacy
Avoids injection
Requires proper technique

Intracavernosal injections:

85-90% efficacy
Alprostadil, papaverine, phentolamine (trimix)
Risk: priapism (5%), fibrosis

Vacuum erection devices:

60-80% satisfaction
No systemic effects
Cumbersome but effective

Cardiovascular Risk Management

ED patients require aggressive risk modification:

Statin therapy (target LDL <70 mg/dL)
Aspirin in appropriate patients
ACE inhibitors/ARBs preferred for hypertension
Aggressive diabetes control (HbA1c <7%)

The Princeton III Consensus stratifies cardiovascular risk:

Low risk: <3 risk factors, asymptomatic → Safe for sexual activity
Intermediate risk: ≥3 risk factors → Stress test before PDE5 inhibitor
High risk: Unstable angina, recent MI → Stabilize before treatment

Clinical Hack #14: Use ED diagnosis as an opportunity for comprehensive cardiovascular risk reduction. Many patients are more motivated to modify risks when sexual function improves.

Special Populations

Diabetic Men

50-75% prevalence of ED
Multifactorial: vascular, neuropathic, hormonal
Often requires higher PDE5 inhibitor doses
Improved glucose control modestly improves ED

Post-Prostatectomy

30-85% develop ED (nerve-sparing procedures lower)
Early rehabilitation with PDE5 inhibitors may preserve function
Consider intracavernosal therapy if refractory

Chronic Kidney Disease

ED in 50-80% of dialysis patients
Low testosterone common
PDE5 inhibitors safe and effective
Address anemia, uremia, medications

When to Refer

Urology referral indicated for:

Peyronie's disease
Priapism
Penile trauma/fracture
Consideration of penile prosthesis
Failure of medical management

Endocrinology referral for:

Pituitary adenoma
Complex hypogonadism
Persistent hyperprolactinemia

Cardiology referral for:

High-risk cardiovascular profile
Abnormal stress testing
Before clearance for sexual activity

Clinical Pearls Summary

ED is a vascular disease—treat it as cardiovascular risk equivalent
Always obtain 8-10 AM testosterone levels
Order HbA1c and lipids in all ED patients
Morning erections suggest psychogenic component
Isolated ED with normal libido = vascular; ED with low libido = hormonal
Check ABI in patients >50 years
The "2-strikes rule" for PDE5 inhibitors
Screen for depression (PHQ-9)
Combination testosterone + PDE5 inhibitor in hypogonadal men
Use ED diagnosis to motivate comprehensive risk reduction

Conclusion

Adult-onset male sexual dysfunction represents far more than an isolated urological concern. For the internist, ED evaluation provides a unique window into cardiovascular health, endocrine function, and overall wellbeing. A systematic approach combining thorough history, targeted investigation, and evidence-based intervention addresses both the immediate concern and underlying systemic pathology.

The modern internist must be comfortable initiating this conversation, conducting appropriate evaluation, and implementing first-line management. This approach not only improves quality of life but may prevent future cardiovascular events—transforming an awkward consultation into potentially life-saving intervention.

Final Pearl: The most important question is the one you ask. Simply inquiring about sexual function opens a diagnostic and therapeutic pathway that many patients desperately need but are too embarrassed to initiate.

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