What is the appropriate evaluation and treatment for erectile dysfunction in a patient after radical orchiectomy and cisplatin‑based chemotherapy?

Erectile Dysfunction After Radical Orchiectomy and Chemotherapy

Erectile dysfunction after radical orchiectomy and cisplatin-based chemotherapy is uncommon because testicular cancer treatment does not directly damage the neurovascular structures responsible for erection, and you should first measure morning serum testosterone and assess for psychogenic factors, cardiovascular risk, or chemotherapy-related vascular injury before initiating PDE5 inhibitor therapy. 1

Understanding the Clinical Context

Radical orchiectomy itself does not cause erectile dysfunction through direct nerve injury, unlike radical prostatectomy or pelvic radiation. 2, 3 The spermatic cord removal occurs at the internal inguinal ring level and does not involve the autonomic nerves (sympathetic T10-L2 and parasympathetic S2-S4) that mediate erectile function. 4

However, several factors may contribute to ED in this population:

Potential Etiologic Factors

Testosterone deficiency:

• Loss of one testis reduces testosterone production, and the remaining testis may not fully compensate. 1
• Cisplatin-based chemotherapy can cause Leydig cell dysfunction, further impairing testosterone synthesis. 5
• Morning serum total testosterone <300 ng/dL defines hypogonadism and warrants replacement therapy. 1

Chemotherapy-related vascular injury:

• Cisplatin causes endothelial damage and small vessel injury similar to radiation-induced changes. 4
• This vascular toxicity can impair penile blood flow and contribute to organic ED. 6, 3

Psychogenic factors:

• Cancer diagnosis, body image concerns after orchiectomy, and fear of recurrence create significant psychological stress. 7
• The presence of preserved morning/nocturnal erections strongly suggests a psychogenic component. 1

Diagnostic Evaluation

Mandatory initial assessment:

• Measure morning (8-10 AM) serum total testosterone on two separate occasions if the first value is low. 1
• Obtain detailed sexual history focusing on timing of ED onset (sudden vs. gradual), presence of morning/nocturnal erections, and masturbatory erections. 1
• Screen for cardiovascular risk factors: diabetes, hypertension, dyslipidemia, smoking, obesity. 1
• Assess for depression, anxiety, relationship conflicts, and cancer-related distress. 1
• Review all medications, particularly if the patient is on anxiolytics or antidepressants. 1

Key diagnostic distinctions:

• Preserved morning erections with situational ED indicates psychogenic etiology. 1
• Loss of all erections (including morning) suggests organic vascular or hormonal causes. 1
• Sudden onset with loss of libido points toward testosterone deficiency. 1

Additional laboratory work:

• Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides). 1
• Fasting glucose or HbA1c to exclude diabetes. 1
• If testosterone replacement is planned: baseline hemoglobin, hematocrit, PSA (if age >40), and liver function tests. 1

Treatment Algorithm

Step 1: Address Testosterone Deficiency First

If morning testosterone is <300 ng/dL on two measurements:

• Initiate testosterone replacement therapy, which improves both erectile function and libido in hypogonadal men. 1
• Testosterone therapy enhances response to PDE5 inhibitors. 1
• Critical contraindication: Do not use testosterone in men with active surveillance for residual disease or those on androgen deprivation therapy. 4
• Monitor hematocrit; withhold if baseline >50% or if on-treatment level exceeds 54%. 1

Step 2: Initiate PDE5 Inhibitor Therapy

First-line pharmacologic treatment regardless of etiology (organic, psychogenic, or mixed):

• Prescribe sildenafil, tadalafil, vardenafil, or avanafil as initial therapy. 1, 6
• Educate that sexual stimulation is necessary for drug efficacy. 1
• Require at least 5 attempts at maximum tolerated dose before declaring treatment failure. 1
• Response rates: 70% post-radiotherapy, 40-50% post-radical prostatectomy, likely intermediate after chemotherapy. 6

Absolute contraindication:

• Concurrent oral nitrate use due to severe hypotension risk. 1

Relative contraindications:

• Myocardial infarction within 90 days, unstable angina, NYHA class II+ heart failure within 6 months, stroke within 6 months, systolic BP <90 mmHg. 1

Combination therapy:

• In hypogonadal men, combining testosterone replacement with PDE5 inhibitors yields superior outcomes compared to PDE5 inhibitors alone. 1

Step 3: Lifestyle Modifications (Concurrent with Pharmacotherapy)

Mandatory counseling for all patients:

• Smoking cessation (reduces mortality by 36% in cardiac patients and improves endothelial function). 1
• Target BMI <30 kg/m² through weight loss. 1
• Regular aerobic exercise (reduces diabetes and cardiovascular disease incidence by 30-50%). 1
• Mediterranean-style diet rich in fruits, vegetables, whole grains, fish. 1
• Limit alcohol to ≤14 units per week. 1
• Optimize control of diabetes, hypertension, and hyperlipidemia. 1

Step 4: Psychological and Sexual Counseling

When to refer:

• Identified depression, anxiety, performance anxiety, or relationship conflict. 1
• Preserved morning erections with situational ED (pathognomonic for psychogenic etiology). 1
• Persistent distress about body image changes after orchiectomy. 4, 7

Evidence for combined approach:

• Psychosexual counseling combined with PDE5 inhibitors yields superior outcomes compared to either modality alone. 1
• Involve the partner in assessment and treatment to improve adherence and outcomes. 1, 7

Step 5: Second-Line Therapies (If Two Different PDE5 Inhibitors Fail)

Refer to urology for:

• Intracavernosal injection of vasoactive agents (alprostadil). 6, 8
• Intraurethral alprostadil suppositories. 6
• Vacuum erection devices. 6, 9
• Penile prosthesis implantation for refractory cases (high patient satisfaction). 1

Critical Clinical Pitfalls

Do not delay testosterone measurement:

• The combination of ED with loss of libido makes testosterone deficiency highly likely and treatable. 1
• Borderline testosterone without hypogonadal symptoms does not require immediate replacement, but confirmed low levels mandate therapy. 1

Do not ignore cardiovascular risk:

• ED serves as an independent predictor of cardiovascular disease, comparable to smoking or family history of MI. 1
• ED can precede coronary symptoms by 2-5 years. 1
• Communicate this cardiovascular risk to the patient's primary care provider. 1

Do not assume psychogenic ED requires only counseling:

• PDE5 inhibitors work for both psychogenic and organic ED and should be initiated concurrently with psychological therapy. 1

Do not treat ED alone when depression is present:

• Address the underlying psychiatric condition, recognizing that antidepressants themselves may worsen sexual function. 1

Do not overlook the specific psychological impact of orchiectomy:

• Body image concerns and loss of testicular tissue can be profoundly distressing, particularly for younger men. 7
• Open discussion about these changes is essential, with referral to supportive counseling when distress is expressed. 4, 7

Prognosis and Expectations

Realistic counseling points:

• ED after testicular cancer treatment is less common and more reversible than after prostate cancer treatment. 2, 3
• If testosterone deficiency is corrected and vascular risk factors are optimized, response to PDE5 inhibitors should approach rates seen in general ED populations. 1, 6
• Early intervention with PDE5 inhibitors may prevent long-term structural changes in penile tissue. 8, 9
• Multidisciplinary approach including hormonal optimization, pharmacotherapy, lifestyle modification, and psychological support offers the best outcomes. 8