Accuracy of the Vermeulen Equation with Elevated SHBG and Low Total Testosterone
The Vermeulen equation may not be accurate for calculating free testosterone when SHBG is elevated (95 nmol/L) and total testosterone is low (40 nmol/L), as this combination can lead to inaccurate estimates of bioavailable testosterone.
Understanding Free Testosterone Calculation Methods
- The Vermeulen equation is commonly used to calculate free testosterone (cFT) from total testosterone (TT) and sex hormone-binding globulin (SHBG) measurements 1.
- Free testosterone represents the biologically active form of testosterone that is unbound to SHBG or albumin, accounting for approximately 2% of total testosterone 2.
- When SHBG levels are significantly elevated, as in your case (95 nmol/L), the accuracy of calculated free testosterone may be compromised 3.
Limitations of the Vermeulen Equation in Your Scenario
- The Vermeulen equation was founded on models of testosterone binding to SHBG that may not be entirely accurate, particularly at extreme values of SHBG 3.
- Research shows that calculated free testosterone using the Vermeulen equation can have mean biases ranging from 5.8% to 56.0% compared to other calculation methods 2.
- When SHBG concentrations are very high (>30 nmol/L), as in your case (95 nmol/L), the accuracy of calculated free testosterone decreases significantly 3, 4.
More Accurate Alternatives for Your Situation
- Direct measurement of free testosterone using equilibrium dialysis is considered the gold standard and would be more appropriate in your case with elevated SHBG 1, 5.
- Morning serum samples should be used for testosterone assessment, as there is significant diurnal variation in levels 1.
- For men with obesity or other conditions that can affect SHBG levels, free testosterone measured by equilibrium dialysis provides more accurate results than calculated methods 1.
Clinical Implications
- In men with normal SHBG levels, total testosterone measurement is often sufficient for diagnosing hypogonadism 6.
- However, when SHBG is elevated (>30 nmol/L) and total testosterone is borderline or low, calculated free testosterone may not accurately reflect the bioavailable testosterone 4.
- Studies show that in certain populations (such as HIV-infected men), a substantial proportion of hypogonadal men have normal total testosterone but low free testosterone, highlighting the importance of accurate free testosterone measurement 5.
Recommendations for Your Case
- With SHBG of 95 nmol/L and total testosterone of 40 nmol/L, direct measurement of free testosterone by equilibrium dialysis is recommended rather than relying on the Vermeulen equation 1, 3, 4.
- If direct measurement is not available, be aware that the calculated free testosterone may underestimate the true free testosterone level due to the elevated SHBG 3, 4.
- Consider repeating the testosterone measurements, ensuring they are taken in the morning (between 8 AM and 10 AM) for the most accurate results 1.
Additional Considerations
- The free androgen index (FAI), calculated as the ratio of total testosterone to SHBG, is not recommended for use in men because of inaccuracy at extremes of SHBG concentration 3.
- When evaluating testosterone status in men with abnormal SHBG levels, clinical symptoms should be considered alongside laboratory values 1.
- If hypogonadism is suspected despite normal calculated free testosterone, further evaluation including luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements may be warranted 1.