Management of a 54-Year-Old Man with Morning Testosterone 352 ng/dL and Free Testosterone 5.9 ng/dL
This patient requires confirmation of testosterone levels with a repeat fasting morning measurement (8-10 AM) before initiating treatment, as his total testosterone of 352 ng/dL falls in the borderline range just above the 300 ng/dL hypogonadism threshold, though his free testosterone appears low. 1, 2, 3
Diagnostic Confirmation Required
Obtain a second fasting morning testosterone measurement (between 8-10 AM) to confirm the diagnosis, as testosterone exhibits significant diurnal variation and single measurements are insufficient for diagnosis 1, 2, 3, 4
Measure both total testosterone and free testosterone by equilibrium dialysis (the gold standard method) in a laboratory certified by an accuracy-based program such as the CDC's Hormone Standardization Program 4, 5
The current total testosterone of 352 ng/dL is technically above the 300 ng/dL threshold used by the American Urological Association to define hypogonadism, but the free testosterone of 5.9 ng/dL requires proper interpretation with validated reference ranges 1
Additional Workup Before Treatment Decision
Measure sex hormone-binding globulin (SHBG) to understand the relationship between total and free testosterone, particularly important in men with obesity where low SHBG can artificially lower total testosterone while free testosterone may be normal 1, 6
If testosterone levels are confirmed low on repeat testing, measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1, 3
If LH/FSH are low (secondary hypogonadism), further evaluation should include serum prolactin, iron saturation, pituitary function testing, and potentially MRI of the sella turcica to identify underlying causes 1
Symptom Assessment Critical for Treatment Decision
Testosterone therapy should only be initiated if the patient has consistent symptoms of hypogonadism along with confirmed low testosterone levels on repeat testing. 2, 3
Key symptoms to assess include:
- Decreased libido and erectile dysfunction 2, 3, 7
- Reduced energy and depressed mood 2, 7
- Loss of muscle mass and strength 2, 3, 7
- Decreased body hair and hot flashes 1
- Reduced bone mineral density 2, 3
Treatment Initiation Criteria
Initiate testosterone therapy only if:
- Morning free testosterone by equilibrium dialysis is frankly low on at least 2 separate assessments 1, 8
- Patient has symptomatic androgen deficiency 2, 3
- Contraindications have been ruled out 2, 3
Absolute Contraindications to Screen For
Do not start testosterone therapy if the patient has:
- Breast or prostate cancer 2, 3
- Prostate-specific antigen >3 ng/mL (or >4 ng/mL per some guidelines) without urological evaluation 2, 3
- Palpable prostate nodule or induration 2, 3
- Hematocrit >50% 2, 3
- Untreated severe obstructive sleep apnea 2, 3
- Severe lower urinary tract symptoms (International Prostate Symptom Score >19) 2, 3
- Uncontrolled or poorly controlled heart failure (class III or IV) 2, 3, 7
Testosterone Formulation Selection if Treatment Indicated
Target mid-normal testosterone levels (500-600 ng/dL) during treatment. 8, 2, 3
Available formulations include:
- Intramuscular testosterone enanthate: 50-400 mg every 2-4 weeks, with most patients not requiring more than 400 mg per month 9
- Transdermal preparations (gels, patches) applied daily, though these may have variable absorption 1, 8, 7
- Buccal, nasal, and subdermal formulations are also available 7
Intramuscular injections avoid absorption variability and may be more reliable for patients who are rapid metabolizers or have inconsistent response to transdermal preparations. 8
Monitoring Protocol Once Treatment Started
- Recheck testosterone levels 2-3 months after initiating therapy or any dose adjustment to allow steady-state levels 8
- For injectable testosterone, measure levels midway between injections 8
- Once stable testosterone levels achieved, monitor every 6-12 months 8, 2, 3
- Continue assessing symptom improvement (energy, libido, muscle mass) alongside laboratory values 8, 2
- Monitor hematocrit, prostate-specific antigen, and prostate examination per standardized protocols 2, 3
Common Pitfall to Avoid
Do not assume this patient requires treatment based on a single borderline testosterone measurement. The total testosterone of 352 ng/dL is just above the diagnostic threshold, and without confirmed low levels on repeat morning testing plus clear hypogonadal symptoms, treatment may not be indicated 1, 2, 3. Many men with obesity have low total testosterone due to low SHBG but normal free testosterone, which does not require testosterone replacement 1, 6.