Diagnosing Low Testosterone in Adult Men
To diagnose low testosterone, obtain two separate fasting morning (8–10 AM) total testosterone measurements using an accurate assay; both values must be <300 ng/dL, and the patient must have specific symptoms—particularly diminished libido or erectile dysfunction—to confirm hypogonadism. 1, 2, 3
Required Laboratory Evaluation
Initial Testosterone Testing
- Measure morning total testosterone between 8:00 AM and 10:00 AM on two separate occasions using the same laboratory and methodology to account for diurnal variation and assay variability 1, 2, 3
- Both measurements must be <300 ng/dL to establish biochemical hypogonadism 1, 2, 3
- Never diagnose on a single measurement or outside the 8–10 AM window, as afternoon/evening values are physiologically lower and lead to false-positive diagnoses 1, 2
Free Testosterone and SHBG Assessment
- In men with total testosterone 231–346 ng/dL (gray zone), obesity, or diabetes, measure free testosterone by equilibrium dialysis (gold standard) and sex hormone-binding globulin (SHBG) 1, 2, 3
- Obese men may have low total testosterone due to reduced SHBG with normal free testosterone, indicating functional rather than true hypogonadism 1, 2
- Calculate the free androgen index (total testosterone ÷ SHBG × 100) when equilibrium dialysis is unavailable; an FAI <30 indicates true hypogonadism 1
Gonadotropin Testing to Determine Etiology
- Measure serum LH and FSH in all men with confirmed low testosterone to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism 1, 2, 4, 3
- Elevated LH/FSH with low testosterone = primary hypogonadism (testicular failure) 1, 4
- Low or inappropriately normal LH/FSH with low testosterone = secondary hypogonadism (pituitary-hypothalamic dysfunction) 1, 4
- This distinction is critical for treatment selection and fertility counseling—secondary hypogonadism may respond to gonadotropin therapy to restore both testosterone and fertility, whereas primary hypogonadism requires testosterone replacement that permanently suppresses spermatogenesis 1, 4
Additional Workup for Secondary Hypogonadism
- Measure serum prolactin if LH/FSH are low or low-normal to screen for hyperprolactinemia 1, 2, 4, 3
- Order pituitary MRI if testosterone <150 ng/dL with LH/FSH <1.5 IU/L (regardless of prolactin), if prolactin >1.5× upper limit of normal, or if visual field defects or anosmia are present 1, 4
- Evaluate for reversible causes: obesity, diabetes, HIV/AIDS, chronic narcotic use, chronic corticosteroid use, hemochromatosis (iron studies), thyroid dysfunction (TSH) 1, 2, 4
Clinical Symptom Assessment
Qualifying Symptoms That Justify Treatment
- Diminished libido and erectile dysfunction are the primary symptoms that correlate with measurable benefit from testosterone therapy 1, 2, 3
- Decreased spontaneous or morning erections reliably improve with testosterone replacement 1
Symptoms With Minimal or No Proven Benefit
- Fatigue, low energy, depressed mood, poor concentration, reduced physical strength, and cognitive complaints show little to no correlation with testosterone levels and minimal improvement with therapy (standardized mean difference ≈0.17 for energy/fatigue) 1, 5, 6
- Do not initiate therapy for nonspecific symptoms alone without confirmed sexual dysfunction 1, 3
Physical Examination Findings
- Evaluate body habitus, BMI, and waist circumference to assess for obesity-related hypogonadism 2
- Assess virilization status: body hair patterns in androgen-dependent areas (chest, face, pubic region) 2
- Examine for gynecomastia (measure serum estradiol if present) 1, 2
- Perform testicular examination to assess volume and consistency; small, firm testes suggest primary hypogonadism 2
- Check for visual field defects (bitemporal hemianopsia suggests pituitary mass) 1
High-Risk Populations Requiring Screening
Measure testosterone even without classic symptoms in men with: 2, 3
- Unexplained anemia
- Decreased bone mineral density or osteoporosis
- Type 2 diabetes mellitus
- HIV/AIDS
- Recent chemotherapy or testicular radiation
- Chronic narcotic or corticosteroid use
- Known pituitary disorders
Baseline Safety Testing Before Treatment
- Hematocrit/hemoglobin: absolute contraindication if >54% 1, 3
- PSA in men >40 years: if >4.0 ng/mL (or >3.0 ng/mL in high-risk groups), require urologic evaluation and negative prostate biopsy before therapy 1, 3
- Fasting glucose and HbA1c to exclude diabetes 1
- Lipid profile for cardiovascular risk assessment 1
- Digital rectal examination to assess for prostate nodules or induration 1, 3
Diagnostic Algorithm Summary
- Obtain two fasting morning (8–10 AM) total testosterone measurements 1, 2, 3
- If both <300 ng/dL, confirm specific symptoms (diminished libido, erectile dysfunction) 1, 3
- Measure LH, FSH, and prolactin to classify primary vs. secondary hypogonadism 1, 2, 4
- In borderline cases (231–346 ng/dL) or obesity, measure free testosterone by equilibrium dialysis and SHBG 1, 2, 3
- If secondary hypogonadism confirmed, evaluate for reversible causes (obesity, medications, pituitary lesions) 1, 2, 4
- Complete baseline safety testing (hematocrit, PSA, glucose, lipids) before initiating therapy 1, 3
Critical Pitfalls to Avoid
- Never diagnose on a single testosterone measurement—two morning values are mandatory 1, 2, 3
- Never test outside 8–10 AM—afternoon values are physiologically lower and cause false positives 1, 2
- Never omit LH/FSH testing—the primary vs. secondary distinction directs treatment and fertility counseling 1, 4
- Never rely on symptoms alone without biochemical confirmation—symptoms are nonspecific and overlap with many conditions 1, 3
- Never start testosterone without confirming the patient does not desire fertility—exogenous testosterone causes prolonged azoospermia 1, 4
- Never skip pituitary imaging when testosterone <150 ng/dL with low gonadotropins—this may miss treatable pituitary lesions 1, 4