Why We Perform Testosterone Panel Blood Tests
We perform testosterone panel blood tests to diagnose hypogonadism (testosterone deficiency) in patients with specific symptoms—particularly diminished libido and erectile dysfunction—and to distinguish between primary (testicular) and secondary (hypothalamic-pituitary) causes, which have fundamentally different treatment implications including fertility preservation. 1, 2
Diagnostic Requirements for Hypogonadism
The diagnosis of testosterone deficiency requires both biochemical confirmation and clinical symptoms—neither alone is sufficient. 1, 2
Biochemical Confirmation
- Two separate morning testosterone measurements (drawn between 8-10 AM) showing levels consistently below 300 ng/dL are required to establish hypogonadism. 1, 2
- Morning timing is critical due to diurnal variation in testosterone levels, with peak levels occurring in early morning. 1, 2
- Both measurements should ideally use the same laboratory and methodology to minimize assay variability. 1
When to Measure Free Testosterone
- Free testosterone by equilibrium dialysis should be measured when total testosterone is borderline (231-346 ng/dL) or in patients with obesity, diabetes, or advanced age. 2, 3
- Elevated sex hormone-binding globulin (SHBG) can artificially lower total testosterone while free testosterone remains normal, creating a discrepancy that masks true hypogonadism. 3, 4
- In men over 60 years presenting with erectile dysfunction, 26.3% have normal total testosterone but low free testosterone—these men have symptomatic hypogonadism that would be missed by screening with total testosterone alone. 4
Distinguishing Primary from Secondary Hypogonadism
Measuring LH and FSH is mandatory to determine the type of hypogonadism, as this distinction has critical treatment implications. 1, 2
Primary (Testicular) Hypogonadism
- Elevated LH/FSH with low testosterone indicates primary hypogonadism. 2, 3
- These men have testicular failure from conditions such as Klinefelter's syndrome, chemotherapy, radiation, orchitis, or testicular torsion. 1, 5, 6
- Treatment is limited to testosterone replacement therapy only—the testes cannot respond to gonadotropin stimulation. 3
- Testosterone therapy permanently compromises fertility by suppressing spermatogenesis and causing azoospermia. 2, 3
Secondary (Hypothalamic-Pituitary) Hypogonadism
- Low or inappropriately normal LH/FSH with low testosterone indicates secondary hypogonadism. 2, 3
- These men have gonadotropin deficiency from pituitary tumors, trauma, radiation, or idiopathic causes. 1, 5
- Gonadotropin therapy (hCG plus FSH) is mandatory for men desiring fertility preservation—testosterone is absolutely contraindicated. 2, 3
- Gonadotropin therapy can restore both testosterone levels and fertility potential by stimulating the testes directly. 3
Additional Testing for Secondary Hypogonadism
- Serum prolactin should be measured in patients with low testosterone combined with low or low-normal LH levels to screen for hyperprolactinemia. 1
- Persistently elevated prolactin levels indicate possible pituitary tumors (prolactinomas) and require endocrinology referral. 1
- Men with total testosterone <150 ng/dL combined with low or low-normal LH should undergo pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be present. 1
Clinical Symptoms That Warrant Testing
Primary Symptoms (Strong Evidence for Benefit)
- Diminished libido and erectile dysfunction are the primary indications for testosterone testing and therapy. 1, 2, 7
- Approximately 36% of men seeking consultation for sexual dysfunction have hypogonadism. 8
- Testosterone deficiency is a common cause of PDE5 inhibitor (sildenafil, tadalafil) failure—a minimal level of testosterone is required for complete effect of these medications. 7
Secondary Symptoms (Weaker Evidence)
- Reduced energy, reduced endurance, diminished work/physical performance, fatigue, depression, reduced motivation, poor concentration, impaired memory, and irritability. 1, 7
- Important caveat: Testosterone therapy produces little to no effect on physical functioning, energy, vitality, or cognition, even in confirmed hypogonadism. 2, 3
- Effect sizes for energy and fatigue are minimal (standardized mean difference 0.17), and improvements in depressive symptoms are less-than-small (SMD -0.19). 3
Physical Signs
- Small, firm testes, reduced virilization (sparse body hair in androgen-dependent areas), gynecomastia, increased body mass index or waist circumference, and testicular abnormalities. 1, 7, 6
High-Risk Populations Requiring Screening
Testosterone should be measured in all patients with the following conditions, even in the absence of symptoms, as they are at high risk for hypogonadism: 1, 2, 7
- Unexplained anemia
- Bone density loss or osteoporosis
- Diabetes mellitus
- Exposure to chemotherapy
- Direct or scatter testicular radiation
- HIV/AIDS
- Chronic narcotic use
- Male infertility
- Pituitary disorders
- Chronic corticosteroid use
Critical Pitfalls to Avoid
Screening Questionnaires Are Inadequate
- Screening questionnaires should not be used at the expense of full patient evaluation and laboratory testosterone measurement. 1
- Specificities and sensitivities vary greatly among available questionnaires, making them ill-suited for screening or as a surrogate for testosterone laboratory testing. 1
Symptoms Alone Are Insufficient
- Approximately 20-30% of men receiving testosterone in the United States do not have documented low testosterone levels before treatment initiation—a practice pattern that violates evidence-based guidelines. 3
- The European Association of Urology explicitly recommends against testosterone therapy in eugonadal men (normal testosterone levels), even if symptomatic, and even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength. 3
Single Measurements Are Unreliable
- Single testosterone measurements are insufficient due to assay variability and diurnal fluctuation. 2, 3
- Repeat measurements are essential to confirm persistent hypogonadism. 2, 3
Don't Diagnose Type While on Testosterone Therapy
- Never attempt to diagnose the type of hypogonadism based on gonadotropin levels while the patient is on testosterone therapy—the results will be misleading. 3
- Testosterone therapy must be discontinued and sufficient washout time (typically 2-4 weeks) allowed before diagnostic testing to differentiate primary from secondary hypogonadism. 3
Expected Treatment Outcomes
Understanding realistic expectations is essential when ordering testosterone panels, as treatment benefits are limited to specific domains:
Proven Benefits
- Small but significant improvements in sexual function and libido (standardized mean difference 0.35). 2, 3
- Modest quality of life improvements, primarily in sexual function domains. 2, 3
- Potential improvements in bone mineral density and correction of mild anemia. 3