What work‑up and management are recommended for a 34‑year‑old man (BMI 27 kg/m²) with fatigue, low libido, occasional erectile dysfunction, difficulty conceiving, hypercholesterolemia, hypertriglyceridemia, elevated low‑density lipoprotein, vitamin D deficiency, and normal prolactin, dehydroepiandrosterone‑sulfate, cortisol suppression test, and ACTH?

Workup and Management Recommendations

Immediate Priority: Evaluate for Hypogonadism and Cardiovascular Risk

Your patient's constellation of fatigue, low libido, erectile dysfunction, and difficulty conceiving strongly suggests testosterone deficiency, which requires immediate measurement of morning serum total testosterone. 1, 2 The abnormal lipid panel (total cholesterol 227, triglycerides 307, LDL 132) and vitamin D deficiency are modifiable cardiovascular risk factors that contribute to both erectile dysfunction and infertility. 2, 3

Essential Laboratory Workup

Testosterone Assessment

• Measure morning (8 AM) serum total testosterone immediately – this is the single most important test given his symptoms of low libido, erectile dysfunction, and infertility concerns. 1, 2, 4
• If testosterone is <300 ng/dL with symptoms present, this confirms hypogonadism requiring treatment. 1
• Testosterone levels between 230-350 ng/dL warrant consideration for a 4-6 month trial of testosterone replacement therapy after discussing risks and benefits. 4

Semen Analysis

• Order semen analysis before initiating any testosterone therapy – testosterone replacement suppresses spermatogenesis and is contraindicated in men actively trying to conceive. 4, 5
• This must be done first if fertility is a current goal.

Additional Endocrine Testing

• The prolactin level of 3.1 ng/mL is normal (typically <20 ng/mL), effectively ruling out hyperprolactinemia as a cause. 6
• DHEA-sulfate of 503 µg/dL is within normal range; DHEA supplementation has not been shown to improve male sexual function. 1, 6
• The dexamethasone suppression test showing cortisol-AM of 0.8 µg/dL with ACTH of 15.5 pg/mL suggests appropriate cortisol suppression, making Cushing's syndrome unlikely.

Metabolic Screening

• Fasting glucose and HbA1c – essential given the dyslipidemia and erectile dysfunction, as diabetes is a major risk factor for both conditions. 2, 7
• Thyroid function tests (TSH, free T4) – hypothyroidism can cause fatigue, low libido, and erectile dysfunction. 6

Cardiovascular Risk Stratification

Erectile dysfunction in a 34-year-old man is a sentinel marker for cardiovascular disease and warrants comprehensive cardiovascular risk assessment. 1, 2 ED often precedes coronary artery disease symptoms by 2-5 years and carries predictive value equivalent to cigarette smoking or family history of myocardial infarction. 2

• Obtain resting electrocardiogram given the dyslipidemia. 4
• Measure blood pressure if not already documented. 4
• Calculate cardiovascular risk score to stratify as low, intermediate, or high risk before initiating any erectile dysfunction treatment. 1, 2

Immediate Management Steps

Lifestyle Modifications (Start Immediately)

• Initiate statin therapy for dyslipidemia – total cholesterol 227 mg/dL, triglycerides 307 mg/dL, and LDL 132 mg/dL all require treatment. Statins improve endothelial function and may enhance erectile function. 1, 3
• Vitamin D supplementation – level of 25.3 ng/mL is deficient (goal >30 ng/mL); replace with 2,000-4,000 IU daily. 2
• Weight reduction – BMI of 27 kg/m² indicates overweight status; even modest weight loss (5-10%) improves erectile function and testosterone levels. 2
• Increase physical activity – regular exercise improves erectile function, cardiovascular health, and testosterone levels. 2, 8
• Smoking cessation if applicable – smoking is a major modifiable risk factor for erectile dysfunction. 1, 8

Triglyceride Management

The triglyceride level of 307 mg/dL is particularly concerning, as pure hypertriglyceridemia may be independently associated with erectile dysfunction in young men. 9 Aggressive lifestyle modification (weight loss, reduced simple carbohydrates, increased omega-3 fatty acids) combined with statin therapy should be initiated. 1

Treatment Algorithm Based on Testosterone Results

If Testosterone <230 ng/dL:

• Refer to endocrinology for testosterone replacement therapy after completing semen analysis. 2, 4
• Testosterone replacement improves libido, erectile function, and may enhance response to PDE5 inhibitors. 1, 2
• Critical caveat: Testosterone therapy must be deferred if the patient is actively trying to conceive, as it suppresses spermatogenesis. 4, 5 Consider referral to reproductive endocrinology/urology for fertility-preserving options (e.g., clomiphene citrate, human chorionic gonadotropin).

If Testosterone 230-350 ng/dL:

• Consider 4-6 month trial of testosterone replacement if symptomatic (low libido, fatigue, erectile dysfunction). 4
• Continue only if clinical benefit is demonstrated after 6 months. 4
• Same fertility considerations apply.

If Testosterone >350 ng/dL:

• Testosterone replacement is not indicated. 4
• Focus on lifestyle modifications, cardiovascular risk reduction, and consider PDE5 inhibitor therapy for erectile dysfunction. 2

Erectile Dysfunction Management

First-Line Pharmacotherapy

• PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are first-line treatment once cardiovascular risk is assessed as low or intermediate. 1, 2
• Start with lowest dose and titrate to maximum as needed for efficacy. 4
• Important: PDE5 inhibitors require adequate testosterone levels for full efficacy; if testosterone is low, address hypogonadism first or concurrently. 1, 2
• Daily low-dose PDE5 inhibitors may be preferable if performance anxiety is a component. 4

Psychosexual Considerations

• Assess for depression and anxiety – these are both causes and consequences of erectile dysfunction. 1, 4
• The presence of morning erections suggests (but does not confirm) a psychogenic component. 1
• Consider referral to mental health professional for cognitive behavioral therapy, which can be used as adjunct to medical treatment. 1, 2, 4
• Include partner in discussions whenever possible – this improves treatment adherence and outcomes. 2, 4

Fertility Considerations

Before any hormonal intervention, establish fertility goals and obtain semen analysis. 4 If fertility is desired:

• Avoid testosterone replacement therapy. 4, 5
• Refer to reproductive endocrinology/urology for fertility-preserving treatment options.
• Address modifiable factors: optimize weight, treat vitamin D deficiency, improve lipid profile, and consider clomiphene citrate or human chorionic gonadotropin to increase endogenous testosterone without suppressing spermatogenesis.

Common Pitfalls to Avoid

• Do not prescribe testosterone without first obtaining semen analysis if fertility is a concern – testosterone suppresses spermatogenesis and can cause irreversible infertility in some men. 4, 5
• Do not prescribe PDE5 inhibitors to patients on nitrates – this combination causes dangerous hypotension. 4
• Do not overlook cardiovascular risk assessment – erectile dysfunction is a sentinel marker for cardiovascular disease requiring comprehensive evaluation. 1, 2
• Do not ignore the lipid abnormalities – dyslipidemia directly impairs erectile function through endothelial dysfunction and must be treated aggressively. 3, 9, 8

Follow-Up and Monitoring

• Recheck testosterone, lipid panel, and vitamin D in 3 months after initiating interventions. 2
• Reassess erectile function and libido at each visit. 2
• Monitor cardiovascular risk factors periodically, as erectile dysfunction and cardiovascular disease share common pathophysiologic pathways. 4
• If testosterone replacement is initiated, monitor hematocrit, PSA (if age-appropriate), and liver function. 5