Elevated Testosterone in Patients Not on Hormone Therapy
When testosterone is elevated in someone not receiving exogenous therapy, immediately measure serum LH to differentiate between surreptitious exogenous use (which suppresses LH) and endogenous overproduction from a testosterone-secreting tumor or other pathologic condition (which maintains or elevates LH). 1
Initial Diagnostic Approach
Measure LH Immediately
The luteinizing hormone level is the critical first test that determines your entire diagnostic pathway 1:
- Suppressed or low LH with elevated testosterone strongly indicates exogenous testosterone use, even if the patient denies it, because exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis 1
- Normal or elevated LH with elevated testosterone indicates endogenous overproduction requiring urgent evaluation for malignancy 1
If LH is Suppressed (Exogenous Source)
Investigate Hidden Sources
- Have a direct conversation about all supplements, over-the-counter products, and substances obtained outside traditional medical channels—patients often don't consider these "hormone therapy" 1
- Consider secondary exposure from a partner using topical testosterone preparations, which transfer through skin contact 1
- Question about use of performance-enhancing substances, bodybuilding supplements, or "anti-aging" compounds 1
Immediate Safety Assessment
- Measure hematocrit/hemoglobin to assess for erythrocytosis, which poses thrombotic risk 1
- Check PSA if male over age 40 to establish baseline and rule out concerning elevations 1
Management After Identifying Source
- Discontinue the source immediately 1
- Obtain serial testosterone measurements every 4-8 weeks to monitor decline toward normal range 1
- Stabilization is defined as two consecutive measurements within 10% of each other 1
- Repeat hematocrit if initially elevated, every 3-6 months until stable 1
If LH is Normal or Elevated (Endogenous Overproduction)
Urgent Endocrinology Referral
This scenario requires immediate referral to endocrinology for evaluation of potential malignancy 1:
- Measure DHEAS to differentiate adrenal from gonadal source of androgen excess 1
- In women, ovarian steroid-cell tumors can produce very high testosterone levels and are clinically malignant in 25-43% of cases 2
- Testicular examination in men to assess for masses, size, consistency, and varicoceles that might indicate estrogen-secreting tumors 3
Additional Workup
- Check for other causes of elevated sex hormone-binding globulin (SHBG) that could artifactually elevate total testosterone 1
- In women with very elevated testosterone but absent virilization, consider laboratory interference and request diethyl ether extraction prior to immunoassay 2
Special Considerations in Women
Polycystic Ovary Syndrome (PCOS)
- PCOS typically causes mild testosterone elevations, not markedly high levels 2
- Functional ovarian hyperandrogenism occurs in approximately 70% of PCOS patients, characterized by excessive 17-hydroxyprogesterone secretion 4
- Functional adrenal hyperandrogenism occurs in about 50% of PCOS patients, with 20-30% having elevated DHEAS 4, 5
Laboratory Interference
- Heterophile antibodies can cause falsely elevated testosterone levels 6
- When clinical presentation doesn't match laboratory values, request liquid chromatography-mass spectrometry for confirmation 6
- Diethyl ether extraction is useful when other methods fail to detect interference 2
Common Pitfalls to Avoid
- Don't assume patient honesty about supplement use—many don't consider over-the-counter products or partner's medications as relevant 1
- Don't delay endocrinology referral when LH is normal/elevated—testosterone-secreting tumors require urgent evaluation 1
- Don't trust a single testosterone measurement—confirm with repeat testing and consider assay interference if clinically discordant 2, 6
- Don't forget to assess thrombotic risk—elevated testosterone can cause dangerous erythrocytosis regardless of source 1