What do you do if a patient's testosterone levels are elevated and they deny using hormone therapy?

Elevated Testosterone Without Reported Hormone Therapy

When a patient presents with elevated testosterone and denies hormone therapy, immediately measure serum LH to differentiate between exogenous testosterone use (suppressed LH) and endogenous overproduction (normal or elevated LH), then pursue the appropriate diagnostic pathway based on this critical distinction. 1

Initial Diagnostic Algorithm

Step 1: Confirm the Elevation and Rule Out Laboratory Error

• Repeat the testosterone measurement using a different assay method, ideally liquid chromatography-mass spectrometry, as heterophile antibodies can cause falsely elevated results in immunoassays 2
• Ensure the sample was drawn in the morning (before 10 AM) when testosterone levels are physiologically highest 3, 4
• Radioimmunological assay following prior sample treatment (extraction or extraction + chromatography) is recommended pending wider availability of mass spectrometry 5

Step 2: Measure Serum LH Immediately

This is the single most important test to guide your next steps:

• Suppressed or low LH with elevated testosterone strongly suggests exogenous testosterone use despite patient denial, as exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis 1, 6
• Normal or elevated LH with elevated testosterone indicates endogenous overproduction from a testosterone-secreting tumor or other pathologic condition 1

If LH is Suppressed (Suggesting Exogenous Use)

Address the Discrepancy Directly

• Have a frank, non-judgmental conversation with the patient about all supplements, over-the-counter products, topical preparations, and any substances obtained outside traditional medical channels 6
• Many patients do not consider supplements, compounded preparations, or products marketed as "testosterone boosters" as "hormone therapy" 6
• Consider secondary exposure from a partner using topical testosterone preparations 6

Immediate Safety Assessment

• Measure hematocrit/hemoglobin to assess for erythrocytosis (hematocrit >50-54%), which poses thrombotic risk 6, 3, 4
• Check PSA if male over age 40 to establish baseline and rule out concerning elevations 7, 6
• Assess for cardiovascular risk factors including blood pressure, signs of fluid retention, and cardiac symptoms 6

Management if Exogenous Use is Confirmed or Strongly Suspected

• Discontinue the source immediately to allow testosterone levels to normalize 8, 6
• Obtain serial testosterone measurements every 4-8 weeks to monitor decline toward normal range, with stabilization defined as two consecutive measurements within 10% of each other 8, 7
• If hematocrit is significantly elevated (>54%), consider therapeutic phlebotomy 6
• Do not resume any testosterone therapy until levels normalize to the middle tertile of the normal reference range 8, 7

If LH is Normal or Elevated (Suggesting Endogenous Overproduction)

Pursue Tumor Workup

When testosterone is twice the upper limit of normal with normal/elevated LH:

• Measure DHEAS to differentiate adrenal from gonadal source 5

  • DHEAS >600 μg/dL suggests androgen-secreting adrenal adenoma and requires adrenal imaging 5
  • Normal DHEAS suggests ovarian hyperthecosis (in females) or testicular tumor (in males), requiring pelvic/testicular ultrasound 5

• Check for other causes of elevated SHBG that could artifactually elevate total testosterone: hyperthyroidism, liver disease, or medications with estrogenic effects (tamoxifen, raloxifene) 5

Endocrinology Referral

• Refer to endocrinology immediately for any patient with confirmed elevated testosterone and normal/elevated LH, as this represents potential malignancy requiring urgent evaluation 1, 5

Critical Pitfalls to Avoid

• Never assume the patient is being truthful about hormone use without biochemical confirmation via LH measurement - the LH level provides objective evidence that cannot be concealed 1, 6
• Do not overlook heterophile antibody interference - if clinical presentation doesn't match the laboratory value, repeat with mass spectrometry 2
• Failure to recognize severely elevated testosterone as a medical urgency - levels significantly above normal require immediate intervention, not routine follow-up 6
• Missing secondary testosterone exposure from a partner's topical preparations, which can transfer through skin contact 6
• Inadequate assessment for erythrocytosis - this is the most common serious complication of elevated testosterone and poses immediate thrombotic risk 6

Monitoring Protocol

Once the source is identified and addressed:

• Serial testosterone measurements every 4-8 weeks until normalization 8, 7
• Repeat hematocrit if initially elevated, every 3-6 months until stable 7, 6
• PSA monitoring every 3-6 months for the first year if initially concerning 7
• If fertility is a concern, counsel that exogenous testosterone suppresses spermatogenesis and recovery can take months to years after cessation 7, 6