Low Testosterone: What Blood Tests to Order

Testosterone evaluation requires more than just a single number. The Endocrine Society guidelines recommend a thorough workup that includes multiple markers to confirm the diagnosis, determine the cause, and rule out contraindications to treatment.

The core testosterone panel should include:

• Total Testosterone — the primary screening test. Normal range for adult men is approximately 264–916 ng/dL (Endocrine Society), though many experts consider optimal to be 500–900 ng/dL. Two morning measurements below 300 ng/dL on separate days are required for a formal diagnosis of hypogonadism.
• Free Testosterone — only 2–3% of testosterone is "free" (unbound) and biologically active. Calculated from total testosterone, SHBG, and albumin. Free T can be low even when total T is normal if SHBG is elevated.
• SHBG (Sex Hormone-Binding Globulin) — this protein binds testosterone and makes it inactive. High SHBG (common with aging, liver disease, hyperthyroidism) artificially inflates total T while reducing free T. Low SHBG (common with obesity, insulin resistance, diabetes) does the opposite.
• LH (Luteinizing Hormone) — produced by the pituitary gland to stimulate testosterone production. LH distinguishes between primary hypogonadism (testicular failure — high LH) and secondary hypogonadism (pituitary/hypothalamic dysfunction — low or normal LH).
• PSA (Prostate-Specific Antigen) — a baseline PSA is essential before starting testosterone replacement therapy (TRT), as exogenous testosterone is contraindicated with untreated prostate cancer.

Timing matters: Testosterone follows a circadian rhythm, peaking between 7–10 AM and declining 20–25% by the afternoon. Always draw testosterone labs in the early morning (before 10 AM) for the most accurate reading.

Understanding the distinction between total and free testosterone is essential for accurate diagnosis. In your blood, testosterone exists in three forms:

• SHBG-bound (60–70%) — tightly bound to Sex Hormone-Binding Globulin. This fraction is biologically inactive and cannot enter cells.
• Albumin-bound (25–35%) — loosely bound to albumin. This fraction can dissociate and become available at tissue level. It's considered "bioavailable."
• Free (2–3%) — completely unbound and immediately active. This is the fraction that binds to androgen receptors and produces effects.

When the numbers disagree: The most common clinical scenario is a man with symptoms of low T whose total testosterone is in the low-normal range (350–450 ng/dL) but whose free testosterone is below normal. This typically happens when SHBG is elevated — something that increases with age, liver disease, hyperthyroidism, and certain medications (anticonvulsants, estrogen).

Conversely, obese men often have low SHBG (driven by insulin resistance), which artificially depresses total testosterone while free testosterone may still be adequate. Losing weight often normalizes SHBG and total testosterone in these cases.

Reference ranges for free testosterone vary significantly by lab and method. Direct analog assays (common at commercial labs) are less accurate than equilibrium dialysis or calculated free T from total T + SHBG. Generally, free testosterone below 5–9 ng/dL (50–90 pg/mL) in men suggests deficiency, depending on the assay used.

Bottom line: always interpret total testosterone alongside SHBG and free testosterone. Any one of these numbers in isolation can be misleading.

Testosterone doesn't exist in a vacuum — several interconnected hormones regulate its production and activity. Testing these supporting markers is what separates a thorough evaluation from a superficial one.

LH (Luteinizing Hormone): LH is the signal from your pituitary gland telling your testes to produce testosterone. It's the most important test for determining the cause of low testosterone:

• Low T + High LH (above 10 mIU/mL) = Primary hypogonadism. Your testes are failing despite adequate stimulation. Causes include Klinefelter syndrome, prior testicular injury, mumps orchitis, varicocele, and aging. Treatment is testosterone replacement.
• Low T + Low or Normal LH = Secondary (central) hypogonadism. Your pituitary isn't sending enough signal. Causes include pituitary tumors, obesity, opioid use, sleep apnea, stress, and overtraining. Treatment may involve addressing the underlying cause, clomiphene citrate, or TRT.

FSH (Follicle-Stimulating Hormone): FSH drives sperm production (spermatogenesis). Elevated FSH with low testosterone suggests primary testicular failure. FSH is especially important to check if fertility is a concern, because TRT suppresses sperm production — sometimes to zero. Men who want to preserve fertility should discuss alternatives like clomiphene or hCG with their provider.

Estradiol: Men produce estradiol through aromatization of testosterone, primarily in fat tissue. Estradiol in men should typically be 20–40 pg/mL. Elevated estradiol (common in obesity) can cause gynecomastia (breast tissue growth), water retention, and mood changes. It can also suppress LH production through negative feedback, worsening low T.

Prolactin: If LH and testosterone are both low, some providers will check prolactin to screen for a prolactinoma (a benign pituitary tumor that suppresses LH). Elevated prolactin (above 20–25 ng/mL) warrants an MRI of the pituitary.

If you're on testosterone replacement therapy (TRT), regular blood work is non-negotiable. The Endocrine Society recommends the following monitoring schedule:

Before starting TRT:

• Confirm low testosterone on two separate morning draws
• Baseline PSA and digital rectal exam (if age ≥40)
• Baseline hematocrit/hemoglobin (CBC)
• Baseline lipid panel
• Assess for sleep apnea, fertility goals, and cardiovascular risk

Monitoring on TRT — check at 3, 6, and 12 months, then annually:

• Total testosterone — target mid-normal range (500–700 ng/dL for most protocols). Draw at trough (right before next injection for IM; any time for daily topicals).
• Hematocrit (CBC) — testosterone stimulates red blood cell production. Hematocrit above 54% increases blood viscosity and clotting risk. If this happens, your dose may need to be reduced or you may need to donate blood.
• PSA — monitor for prostate changes. A rise greater than 1.4 ng/mL within 12 months or above 4.0 ng/mL warrants urology referral. Note: testosterone does not cause prostate cancer, but it can accelerate growth of an existing cancer.
• Estradiol — monitor for symptoms of excess estrogen (water retention, breast tenderness, mood). An aromatase inhibitor may be added if estradiol climbs above 40–50 pg/mL with symptoms.
• Lipid panel — TRT can lower HDL cholesterol. Monitor and manage cardiovascular risk factors proactively.

Important note: If you started TRT and want to discontinue, taper under medical supervision. Abrupt cessation can cause a prolonged period of very low testosterone while your hypothalamic-pituitary-gonadal axis recovers — a process that can take weeks to months.