Why Check Free Testosterone and SHBG in This Patient
Despite normal total testosterone levels, free testosterone and SHBG should be checked because total testosterone alone does not accurately reflect bioavailable testosterone status, and hyperprolactinemia can alter SHBG levels, potentially masking persistent hypogonadism even when total testosterone appears normal.
Understanding the Limitation of Total Testosterone
Total testosterone measurements include both protein-bound (biologically inactive) and free (biologically active) testosterone. The bioavailable fraction—what actually matters clinically—depends on SHBG levels, which can be significantly affected by various factors including:
- Hyperprolactinemia itself can alter SHBG levels, potentially creating a discordance between total and free testosterone 1
- A total testosterone of 410 ng/dL in the morning sits in the lower-normal range, which may still be associated with hypogonadal symptoms if free testosterone is low 1
Clinical Significance of Free Testosterone Assessment
The free testosterone measurement provides critical information that total testosterone cannot:
- Free testosterone represents the biologically active hormone that actually binds to androgen receptors and produces clinical effects 1
- Patients can have "normal" total testosterone but low free testosterone if SHBG is elevated, resulting in persistent symptoms of hypogonadism 1
- Conversely, if SHBG is low, free testosterone may be adequate despite borderline total testosterone 1
Why SHBG Matters Specifically
SHBG measurement is essential because:
- SHBG levels determine how much testosterone is bioavailable versus bound and inactive 1
- Prolactin levels, even when controlled, may have previously affected SHBG production, and this effect may persist 1
- Without knowing SHBG, you cannot accurately interpret whether the total testosterone of 410 ng/dL represents adequate androgen activity 1
Assessing Treatment Adequacy
Even though prolactin is now controlled (<48 ng/mL) on cabergoline 0.25 mg twice weekly:
- The goal of treating hyperprolactinemia includes restoration of normal gonadal function, not just prolactin normalization 1
- Some patients may have persistent hypogonadism despite prolactin control, requiring either dose adjustment of cabergoline or additional interventions 1
- Free testosterone and SHBG help determine if the current cabergoline dose is adequate for full restoration of the hypothalamic-pituitary-gonadal axis 1
Common Clinical Pitfall
A critical mistake is assuming that normalized prolactin automatically means normalized testosterone function. The total testosterone of 410 ng/dL may represent:
- Adequate androgen status if SHBG is low (high free testosterone) 1
- Persistent hypogonadism if SHBG is elevated (low free testosterone despite "normal" total) 1
Without these additional measurements, you risk under-treating a patient who continues to experience hypogonadal symptoms despite biochemical "control" of their prolactin.