The Free Hormone Hypothesis
Why only unbound testosterone enters cells
Evidence grade 3 of 5, Mixed. Read how the Atlas grades evidence.
The written rationale for this grade is still being prepared.
- FDA
- Not applicable (physiology)
Reference only. Not medical advice.
This is something to take to a clinician. The Atlas can tell you what is known about the free hormone hypothesis in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
The free hormone hypothesis holds that only unbound testosterone (~2-3%) can diffuse into cells and act, while SHBG-bound testosterone is a sequestered reserve. This is why free (or bioavailable) testosterone, not just total, is the clinically relevant fraction and why SHBG so strongly shapes symptoms. The modern caveat: the strict version is debated, some tissues may take up albumin-bound (and possibly SHBG-bound, via megalin-mediated endocytosis) testosterone, so 'free' is the best practical marker but not a perfectly clean line. Calculated free testosterone (Vermeulen equation) is the usual estimate.
The principle behind 'free testosterone', with an important modern caveat.
What it is invoked to explain
Claims this idea is used to support. Whether it supports them is the rest of the entry.
How it is supposed to work
Lipophilic testosterone equilibrates between free, albumin-bound (loosely), and SHBG-bound (tightly) pools; classically only the free fraction diffuses across membranes to bind intracellular AR. Some evidence for receptor-mediated uptake of bound hormone (e.g., megalin) complicates the strict model, but free/bioavailable testosterone remains the most clinically useful fraction. Because direct free-T assays are unreliable, calculated free testosterone from total T, SHBG, and albumin (Vermeulen) is preferred.
What people get wrong
Often saidBound testosterone is permanently useless
ActuallySHBG-bound testosterone is a dynamic reserve, and some bound hormone may be taken up by specific tissues. Free testosterone is the best practical marker, not an absolute on/off line.
Who profits, and who pushes back
Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.
At a glance
- Free fraction
- ~2-3% (unbound)
- Reserve
- SHBG-bound (~40-45%)
- Caveat
- Strict free-only model is debated
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about The Free Hormone Hypothesis. A short entry is not a safe entry.
- Timeline. We have not built the dated record of research and regulatory events.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- What could change. No forward-looking summary yet.
- How it compares. We have not set it against the alternatives.
- Children and teenagers. We have not checked what is known about younger people.
- What can go wrong. We have not written the risk line for this one. Read the safety section below rather than treating its absence as reassurance.
- Where we land. We have not taken a position on this yet.
Sources
No sources recorded for this entry yet. Nothing on this page can be checked against a citation until that changes, so treat it as a summary awaiting its evidence.