Detailed definition
Sex hormone-binding globulin is synthesized in the liver and binds androgens (with high affinity) and estrogens (with lower affinity) in serum. Only the unbound (free) fraction is biologically active. SHBG is regulated by hormones, metabolic state, and hepatic factors: estrogens (especially oral) raise SHBG; androgens, insulin, and thyroid abnormalities can lower it. Oral estrogen typically doubles or more SHBG levels through first-pass hepatic stimulation, which can substantially reduce free testosterone — a relevant consideration for women with concurrent low libido or those starting low-dose testosterone therapy. Transdermal estrogen does not raise SHBG meaningfully. Lab interpretation: SHBG itself is rarely the primary lab ordered, but it is essential context for interpreting total testosterone in women, since the free or bioavailable fraction is what matters clinically.
Why it matters in menopause
For postmenopausal women on oral estrogen who develop or worsen low libido, the rise in SHBG and consequent fall in free testosterone is one mechanism. Switching from oral to transdermal estrogen often improves the picture without requiring testosterone supplementation.
Related terms
Sources
External references: Wikipedia.