Evaluation and Management Approach
Initial Diagnostic Workup Required
Your patient's testosterone levels (391 ng/dL total, 3.8 ng/dL free) are in the low-normal range and do not meet diagnostic criteria for hypogonadism, which requires levels consistently below 300 ng/dL on two separate morning measurements. 1, 2 Before considering any treatment, you must complete the following diagnostic evaluation:
Essential Laboratory Tests to Order:
Repeat morning total testosterone (8-10 AM) - A single measurement is insufficient due to assay variability and diurnal fluctuation; you need confirmation with at least two separate morning measurements showing levels <300 ng/dL to establish biochemical hypogonadism 1, 2
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) - These distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism, which has critical treatment implications including fertility preservation 1, 3
Sex hormone-binding globulin (SHBG) - Essential when total testosterone is borderline, as this helps distinguish true hypogonadism from low SHBG-related decreases 1
Prolactin level - To investigate for hyperprolactinemia as a reversible cause of secondary hypogonadism 1
Complete blood count with hematocrit - Baseline documentation required before any testosterone therapy consideration, as hematocrit >54% is an absolute contraindication 1, 3
Thyroid-stimulating hormone (TSH) - Thyroid dysfunction commonly causes fatigue and must be excluded 1
Hemoglobin A1c and fasting glucose - To assess for diabetes, which can cause both fatigue and secondary hypogonadism 1
Vitamin D level - Deficiency commonly presents with fatigue 1
Critical Clinical Context
The primary indication for testosterone therapy is diminished libido and sexual dysfunction, NOT fatigue or low energy. 1, 2 The evidence is unequivocal:
Testosterone produces only minimal improvements in energy and fatigue with a standardized mean difference of just 0.17 - an effect size too small to be clinically meaningful 2, 4
Testosterone provides "less-than-small improvement" in vitality and fatigue across multiple high-quality randomized controlled trials 2
Even in confirmed hypogonadism, testosterone has little to no effect on physical functioning, energy, vitality, or cognition 1, 2
PSA Considerations
Your patient's PSA of 2.7 ng/mL requires careful monitoring but is not a contraindication to testosterone therapy if hypogonadism is confirmed. However:
During testosterone treatment, 5% of men experience PSA increases ≥1.7 ng/mL and 2.5% have increases ≥3.4 ng/mL 5
Urologic referral for biopsy is indicated if PSA increases >1.0 ng/mL during the first 6 months or >0.4 ng/mL per year thereafter 1
PSA >4.0 ng/mL requires urological evaluation and documented negative prostate biopsy before initiating therapy 1, 3
Treatment Algorithm IF Hypogonadism is Confirmed
Only proceed with testosterone therapy if repeat testing confirms total testosterone <300 ng/dL on two separate occasions AND the patient has diminished libido or erectile dysfunction as primary symptoms. 1, 2 If these criteria are met:
First-Line Treatment Selection:
Intramuscular testosterone cypionate or enanthate 100-200 mg every 2 weeks is preferred over transdermal formulations due to significantly lower cost ($156.24 vs $2,135.32 annually) with similar clinical effectiveness 1, 4
Target mid-normal testosterone levels (500-600 ng/dL) measured midway between injections 1
Alternative: Transdermal testosterone gel 1.62% starting at 40.5 mg daily if patient strongly prefers convenience despite higher cost 1, 6
Monitoring Requirements:
Testosterone levels at 2-3 months after initiation, then every 6-12 months once stable 1, 3
Hematocrit monitoring periodically; withhold treatment if >54% 1, 3
PSA monitoring in men over 40 years with the thresholds noted above 1, 3
Reevaluate symptoms at 12 months and discontinue testosterone if no improvement in sexual function occurs 1, 4
Alternative Approaches for Fatigue
Since your patient's testosterone is not clearly low and fatigue is the primary complaint:
Weight loss through low-calorie diets and regular exercise can improve testosterone levels in men with obesity-associated secondary hypogonadism 1
Address reversible causes: sleep disorders, thyroid dysfunction, anemia, vitamin D deficiency, metabolic syndrome 1
If secondary hypogonadism is confirmed (low LH with low testosterone) and patient desires fertility preservation, consider clomiphene citrate 25-50 mg daily as first-line therapy instead of testosterone 2
Critical Pitfall to Avoid
Approximately 20-30% of men receiving testosterone in the United States do not have documented low testosterone levels before treatment initiation, which violates evidence-based guidelines. 1, 2 Do not prescribe testosterone based on symptoms alone without confirmed biochemical hypogonadism with two measurements below 300 ng/dL. 2