SHBG

A liver protein that binds most circulating testosterone and estradiol, so it determines how much of a total hormone reading is actually available to tissue.

Why it matters for hormone results

Most testosterone in blood is bound: tightly to SHBG and loosely to albumin. Only a small fraction circulates unbound. Because SHBG sets how much is locked away, two people with identical total testosterone can have very different free testosterone.

This is the single most common reason a total testosterone result is misread. High SHBG makes a normal total look better than the person feels. Low SHBG does the reverse.

What moves it

SHBG rises with age, thyroid hormone excess, estrogen exposure, liver disease and low calorie intake. It falls with insulin resistance, obesity, hypothyroidism, corticosteroids and androgen use.

That second list is why SHBG functions as a quiet metabolic marker. Low SHBG is associated with incident type 2 diabetes, independently of testosterone, which is a striking finding for a protein most people encounter only as a footnote on a hormone panel.

How it is used

Free testosterone is either measured directly by equilibrium dialysis, which is accurate and uncommon, or calculated from total testosterone, SHBG and albumin using the Vermeulen equation, which is what most laboratories report.

Endocrine Society guidance recommends measuring free testosterone when a total result is borderline or when SHBG is expected to be abnormal, which covers most of the people asking the question.

When hormone questions come up we recommend SHBG alongside total testosterone, because interpreting the total without it is guesswork.

References

  1. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999.
  2. Bhasin S, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018.
  3. Ding EL, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009.