Unraveling the Hormone Mystery: Bioavailable vs. Bio-unavailable Explained!

Let’s delve deeper into the distinction between free-fractioned (bioavailable) hormones and protein-bound (bio-unavailable) hormones, as well as how they are tested:

1. Free-fractioned (Bioavailable) Hormones:

  • Definition: These are hormones that are not bound to any proteins in the bloodstream. They are “free” and are readily available to bind to hormone receptors in various tissues, making them active or “bioavailable.”
  • Significance: Since they can directly interact with cells and tissues, these free hormones are biologically active and play crucial roles in a variety of physiological processes.
  • Serum Testing: Very expensive and not paid for by insurance. Thus, Medical Doctor do not use this method.
    • The most common method to measure free-fractioned hormones is by using equilibrium dialysis. In this procedure, a sample is placed in a dialysis chamber, and the unbound (free) hormones move through a membrane, while protein-bound hormones stay behind. The concentration of free hormones is then measured in the dialysate.
  • Urine/Saliva Testing: The unbound (free) fraction of a hormone that has left the bloodstream to enter target tissues in the body. This unbound fraction is present and measurable in saliva or urine. Not measurable in standard serum blood tests. 
Three years on BiEst & Progesterone Hormone Replacement
Patient was working with a “Bio-Identical” Medical Doctor prescribing transdermal BiEST 2.5 Cream and a “Functional” Doctor using Progesterone/Estrogen Ratios to recommend Progesterone cream. Neither Doctors could explain the diffence in the results.

2. Protein-bound (Bio-unavailable) Hormones:

  • Definition: These hormones are attached to carrier proteins in the bloodstream, like sex hormone-binding globulin (SHBG) or albumin. Due to this binding, they are not immediately available to interact with cells and tissues.
  • Significance: Even though they are bound and not immediately active, these hormones serve as a reservoir. When the body needs more of a particular hormone, these can be released from their binding proteins, becoming bioavailable.
  • Testing: Most standard hormone blood tests measure the total concentration of a hormone, which includes both the free and protein-bound fractions. To determine the concentration of protein-bound hormones, one would subtract the free hormone concentration from the total.

3. Why the distinction matters:

Understanding the balance between free and protein-bound hormones is vital because:

  • While the total hormone level might be within a normal range, the level of bioavailable hormone could be abnormally high or low, leading to symptoms of hormone imbalance.
  • Only free-fractioned hormones can readily exert effects on target tissues. Thus, they are a better indicator of hormonal activity in the body.


When assessing hormone status, especially in cases of suspected hormonal imbalances, it’s crucial to understand both total and free hormone levels. This comprehensive approach offers a more accurate representation of hormonal activity in the body. If you feel your healthcare provider is not addressing this distinction adequately, consider seeking a second opinion or consulting a specialist in endocrinology or integrative medicine.