Interpretation and Management of Testosterone Levels
What These Values Mean
Your testosterone level of 316 ng/dL with a free testosterone of 3.0 ng/dL (approximately 104 pmol/L) falls in a borderline zone that requires confirmation before initiating treatment. 1
Laboratory Assessment
- Total testosterone at 316 ng/dL is just above the diagnostic threshold of <300 ng/dL that defines hypogonadism, but this single measurement is insufficient for diagnosis 1
- Free testosterone at 3.0 ng/dL appears low if using typical reference ranges (normal adult male range approximately 5-21 ng/dL or 115-577 pmol/L), though interpretation depends on your laboratory's specific reference range and measurement method 2, 3
- The discordance between borderline-low total testosterone and potentially low free testosterone suggests you may have altered sex hormone-binding globulin (SHBG) levels 1, 4
Critical Diagnostic Requirements
You cannot be diagnosed with testosterone deficiency based on these numbers alone—diagnosis requires BOTH low testosterone levels AND symptoms of hypogonadism. 1, 5
Diagnostic Algorithm
Step 1: Confirm the Laboratory Values
- Repeat morning total testosterone measurement (between 8-10 AM) on a separate day using the same laboratory and methodology 1, 5
- Both measurements must be consistently <300 ng/dL to meet diagnostic criteria for hypogonadism 1
- Request measurement of SHBG and albumin to calculate free testosterone more accurately, as direct free testosterone assays can be unreliable 6, 3
- Ensure fasting state for blood draw 7
Step 2: Assess for Symptoms and Signs
Evaluate for these specific hypogonadism symptoms: 1, 5
- Reduced libido or sex drive
- Erectile dysfunction or changes in erectile function
- Persistent fatigue, reduced energy, or reduced endurance
- Diminished work or physical performance
- Depression, reduced motivation, or irritability
- Poor concentration or impaired memory
- Male infertility
- Hot flashes
Physical examination findings to document: 1, 5
- Body mass index or waist circumference (obesity commonly causes low SHBG and borderline-low total testosterone with normal free testosterone) 1
- Reduced body hair in androgen-dependent areas
- Gynecomastia
- Testicular size, consistency, and presence of masses
- Presence of varicocele
Step 3: Determine Etiology
If confirmed low testosterone with symptoms, measure luteinizing hormone (LH) to distinguish primary from secondary hypogonadism: 1, 5
- High LH = primary hypogonadism (testicular failure)
- Low or low-normal LH = secondary hypogonadism (pituitary-hypothalamic dysfunction)
If LH is low or low-normal, measure serum prolactin to screen for hyperprolactinemia and possible pituitary tumors 1, 5
Step 4: Screen for High-Risk Conditions
Measure testosterone even without symptoms if you have: 1, 5
- Unexplained anemia
- Bone density loss or osteoporosis
- Diabetes mellitus
- History of chemotherapy or testicular radiation
- HIV/AIDS
- Chronic narcotic use
- Chronic corticosteroid use
- Pituitary dysfunction
Treatment Decision
When NOT to Treat
Do not initiate testosterone replacement therapy if: 1, 2
- Free testosterone is normal (which may be your case if obesity-related low SHBG is present)
- You lack symptoms of hypogonadism
- Only one testosterone measurement has been obtained
- Contraindications exist: prostate or breast cancer, PSA >4 ng/mL (or >3 ng/mL if African-American or family history of prostate cancer), hematocrit >50%, severe untreated sleep apnea, severe lower urinary symptoms (IPSS >19), or uncontrolled heart failure 6
When to Treat
Initiate testosterone replacement therapy when: 1, 8, 9, 8
- Morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments 1
- Symptoms and/or signs of hypogonadism are present 1
- Hypogonadism workup has ruled out other etiologies unrelated to primary or secondary testicular dysfunction 1
Treatment Options
If treatment is indicated, choose from FDA-approved formulations: 8, 9, 8
Transdermal testosterone gel (preferred for stable levels): 1, 8
- Starting dose: 40.5 mg daily (testosterone gel 1.62%) applied to shoulders and upper arms each morning
- Titrate based on pre-dose morning testosterone at 14 and 28 days
- Target mid-normal testosterone range (350-750 ng/dL)
- Critical safety warning: Wash hands after application and cover application sites to prevent secondary exposure to children or women 8
Intramuscular testosterone injections (alternative): 1, 9
- Advantage: avoids daily administration and risk of transfer to others
- Disadvantage: fluctuating testosterone levels between injections
Monitoring on Treatment
Follow-up testosterone levels: 8, 6
- Check at 14 days and 28 days after starting or dose adjustment
- Target mid-normal range (350-750 ng/dL)
- Periodic monitoring thereafter
Safety monitoring: 6
- Hematocrit (risk of polycythemia)
- Prostate-specific antigen and digital rectal exam
- Symptom response assessment
Common Pitfalls to Avoid
- Do not diagnose hypogonadism based on a single testosterone measurement 1, 5
- Do not measure testosterone at random times of day—diurnal variation makes afternoon/evening values unreliable 1, 5
- Do not overlook free testosterone in obese patients, as low SHBG can cause misleadingly low total testosterone with normal free testosterone 1, 5
- Do not treat based on symptoms alone without laboratory confirmation 2, 5
- Do not use screening questionnaires as a substitute for proper evaluation and laboratory testing 1, 5