Do you draw free or total testosterone levels for patients presenting with hypolibidinism (low libido)?

Measuring Testosterone in Low Libido: Free vs Total

You should measure both total testosterone AND free testosterone in patients presenting with low libido, starting with total testosterone and then adding free testosterone measurement when total testosterone is low or borderline-low. 1

Initial Testing Approach

• Begin by measuring total testosterone with a morning sample (between 8-10 AM) due to diurnal variation, with highest levels occurring in the morning 1
• If the initial total testosterone is low (<300 ng/dL), confirm with a second morning measurement before proceeding further 1
• Free testosterone measurement is essential after confirming low or borderline total testosterone to determine if true testosterone deficiency exists 1

Why Free Testosterone Matters

The critical issue is that total testosterone alone misses a significant proportion of hypogonadal patients, particularly in specific populations:

• In men presenting with erectile dysfunction, 17.2% had normal total testosterone but low free testosterone 2
• Among men over 60 years with erectile dysfunction, this rate increased to 26.3% with normal total testosterone but low free testosterone 2
• Total testosterone determination misdiagnosed hypogonadism in 8.4% of men with sexual symptoms when free testosterone was not measured 3
• In patients with borderline total testosterone levels, only 24.7% actually had confirmed hypogonadism when free testosterone was measured 3

The Mechanism Behind This Discrepancy

• Normal or elevated sex hormone-binding globulin (SHBG) with low total testosterone may indicate normal free testosterone levels in some cases, meaning no true deficiency exists 1
• Conversely, elevated SHBG (>50 nmol/L) can cause low free testosterone despite normal total testosterone, particularly in aging men 2
• Patients with normal total testosterone but low free testosterone tend to be older (mean age 65.6 vs 56.8 years) and have significantly higher SHBG levels 2

Optimal Measurement Strategy

Free testosterone should be measured by equilibrium dialysis, which is the gold standard method 1, 4

Alternatively, calculated free testosterone based on total testosterone, SHBG, and albumin is acceptable when equilibrium dialysis is unavailable 2, 3

Clinical Decision Algorithm

1. Measure morning total testosterone (8-10 AM, fasting preferred) 1, 4
2. If total testosterone <300 ng/dL: Repeat morning total testosterone 1
3. If confirmed low or borderline (approximately 250-350 ng/dL): Measure free testosterone, SHBG, and albumin 1, 2
4. Measure LH in all patients with confirmed low testosterone to establish etiology 5, 1
5. If free testosterone is normal despite low total testosterone: testosterone replacement is not indicated 1
6. If free testosterone is confirmed low: consider testosterone replacement therapy 1

High-Risk Populations Requiring Free Testosterone

Always measure free testosterone in addition to total testosterone in:

• Men over 60 years old with sexual symptoms (26.3% miss rate with total testosterone alone) 2
• Obese patients (increased aromatization and altered SHBG) 1
• Patients with borderline total testosterone (250-350 ng/dL range) 3

Critical Pitfall to Avoid

Do not rely solely on total testosterone to exclude hypogonadism in patients presenting with low libido, especially in older men, as this will miss a substantial proportion of patients with true androgen deficiency 2, 3. The historical practice of measuring only total testosterone has been shown to have inadequate diagnostic accuracy 6, 3.