Management of Low Free Testosterone with Normal SHBG and Total Testosterone
Testosterone replacement therapy is indicated for this patient with a low free testosterone level of 126.7 pg/mL despite having a normal sex hormone-binding globulin (SHBG) level of 31.2 and normal total testosterone of 569.3 ng/dL.
Diagnostic Assessment
- The patient's laboratory values show a classic pattern of isolated low free testosterone (126.7 pg/mL) with normal total testosterone (569.3 ng/dL) and normal SHBG (31.2 nmol/L) 1
- Free testosterone percentage of 2.6% is below the expected normal range, confirming testosterone deficiency despite normal total testosterone 1
- This pattern requires treatment if accompanied by clinical symptoms of hypogonadism 2, 1
- Free testosterone measurement is essential in cases where total testosterone and SHBG levels may not reflect true testosterone status 1, 3
Clinical Correlation
Before initiating treatment, confirm the presence of symptoms associated with testosterone deficiency, such as: 2, 1
- Decreased energy, endurance, or physical performance
- Fatigue, depression, reduced motivation
- Poor concentration or memory
- Reduced sex drive or erectile dysfunction
- Changes in body composition
Physical examination should evaluate: 2
- Body habitus and virilization status
- Body mass index/waist circumference
- Presence of gynecomastia
- Testicular size and consistency
Additional Testing
- Measure morning luteinizing hormone (LH) levels to determine if hypogonadism is primary (testicular) or secondary (pituitary-hypothalamic) 2, 1
- If LH is low or low-normal with low free testosterone, measure serum prolactin to rule out hyperprolactinemia 2
- Consider measuring estradiol if the patient presents with breast symptoms or gynecomastia 2
- If fertility is desired, a reproductive health evaluation should be performed prior to treatment 2
Treatment Approach
For patients with confirmed low free testosterone on at least two separate assessments, testosterone replacement therapy is indicated 2, 1
Transdermal testosterone preparations (gel, patch) are generally preferred as first-line options because: 2
- They produce stable day-to-day testosterone levels
- They avoid the discomfort of intramuscular injections
- They provide consistent testosterone replacement
Alternative options include: 2
- Testosterone injections (benefit: avoid daily administration, lower cost)
- Implantable testosterone pellets (benefit: longer-term option)
The method of testosterone replacement should be individualized based on patient preference, cost considerations, and specific patient factors 2
Monitoring
- After initiating treatment, monitor testosterone levels at 2-3 months and after any dose change 2
- Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 2
- For patients receiving testosterone injections, levels should be measured midway between injections 2
- Target normal free testosterone levels rather than just total testosterone 1, 3
Common Pitfalls and Caveats
- Relying solely on total testosterone can miss true testosterone deficiency in patients with normal SHBG 1, 3
- Screening questionnaires alone are not appropriate for identifying candidates for testosterone therapy 2
- Direct immunoassays for free testosterone are often inaccurate; calculated free testosterone or equilibrium dialysis methods are preferred 4, 3
- In obese patients, low free testosterone with normal total testosterone can occur due to increased aromatization of testosterone to estradiol in adipose tissue 1