Recommended Medical Work-Up for Low Testosterone
Obtain two separate morning (8-10 AM) total testosterone measurements using the same laboratory and methodology, with diagnosis requiring levels consistently <300 ng/dL on both measurements PLUS the presence of clinical symptoms. 1, 2
Initial Laboratory Testing
Primary Diagnostic Tests
- Measure total testosterone on two separate mornings between 8-10 AM using the same laboratory to confirm diagnosis—never measure at random times due to diurnal variation, as afternoon/evening measurements will be physiologically lower and lead to false-positive diagnoses. 1, 2
- Both measurements must be <300 ng/dL to meet diagnostic criteria for testosterone deficiency. 1, 2
- Clinical symptoms MUST be present alongside low testosterone levels—laboratory values alone are insufficient for diagnosis. 2, 3
Etiology Determination
- Measure serum luteinizing hormone (LH) in ALL patients with confirmed low testosterone to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism. 1, 2
- Measure serum prolactin if LH is low or low-normal to screen for hyperprolactinemia and possible pituitary tumors. 1, 2
Special Circumstances Requiring Free Testosterone
- Measure free testosterone by equilibrium dialysis when total testosterone is near the lower limit of normal (borderline cases). 1, 2
- Measure free testosterone in obese patients because low total testosterone may be due solely to low sex hormone-binding globulin (SHBG) with normal free testosterone—if free testosterone is normal, testosterone replacement is NOT indicated. 2, 4
- In patients with chronic liver disease and elevated SHBG, express testosterone as a ratio of total testosterone/SHBG. 1
Clinical Assessment Required
Symptom Documentation
Document the following symptoms, as they must be present for diagnosis: 1, 2
- Reduced libido or sex drive
- Erectile dysfunction
- Persistent fatigue, reduced energy, and diminished endurance
- Decreased work and physical performance
- Depression, reduced motivation, poor concentration, or impaired memory
- Male infertility
- Gynecomastia
Physical Examination Findings
Perform targeted examination evaluating: 1, 2
- Body mass index and waist circumference
- Body hair patterns in androgen-dependent areas (virilization status)
- Presence of gynecomastia
- Testicular size and consistency
- Prostate examination for abnormal size or morphology
- Presence of varicocele
Red Flag Symptoms Requiring Additional Workup
- Bitemporal hemianopsia suggests pituitary pathology—requires MRI of sella turcica. 1
- Anosmia suggests Kallmann syndrome. 1
High-Risk Populations Requiring Testing Even Without Symptoms
Measure testosterone in the following conditions regardless of symptom presence: 1, 2
- Unexplained anemia
- Diabetes mellitus
- Bone density loss or osteoporosis
- History of chemotherapy or testicular radiation exposure
- HIV/AIDS
- Chronic narcotic or corticosteroid use
- Pituitary dysfunction
- Male infertility
Additional Workup for Secondary Hypogonadism
If LH is low or low-normal, indicating secondary hypogonadism: 2
- Consider iron saturation studies
- Perform comprehensive pituitary function testing
- Obtain MRI of the sella turcica to evaluate for pituitary pathology
Critical Pitfalls to Avoid
- Do NOT diagnose hypogonadism based on a single testosterone measurement—two separate morning measurements are mandatory. 1
- Do NOT measure testosterone at random times of day—this leads to false-positive diagnoses due to normal diurnal variation. 1, 2
- Do NOT rely on screening questionnaires alone—they have variable specificity and sensitivity and cannot establish diagnosis. 1, 4
- Do NOT overlook free testosterone in obese patients—they may have low total testosterone with normal free testosterone due to low SHBG, and treatment would be inappropriate. 1, 2
- Do NOT initiate treatment without confirming both low testosterone levels AND clinical symptoms—both criteria must be met. 2, 3