Estrogen transport and availability

Estrogen transport

ESTRADIOL (E2) is transported in serum, reversibly bound to sex hormone-binding globulin (SHBG) and, with less affinity, to albumin

Sex hormone-binding carriers

Estrogen bioavailabilty

The bioavailability of estrogens is modulated by their binding to the sex hormone-binding carrier SHBG

•  40% of ESTRADIOL (E2) is bound with high affinity to SHBG

•  59% remainder is loosely attached to albumin - both the free and the albumin-bound E2 are bioavailable to various tissues.

•  ~2% of E2 circulates as a free steroid

Exogenous oral estrogensstimulate increased SHBG production(in the liver cells), whereas androgens suppress SHBG levels(making E2 more bioavailable, since there is less SHBG to bind to).

-   Potency of different estrogens is reflected in their ability to bind to SHBG and to stimulate its hepatic synthesis - E.g.Unconjugated equilin (one of the estrogens isolated from horse urine E.g. in Premarin), ESTRONE (E1), and ESTRADIOL (E2) bind with high but different affinities to SHBG. In a comparative study, 0.625 mg conjugated equine estrogens (CEE) increased plasma SHBG by 100% over baseline after 3 months of treatment; 1 mg of oral E2 increased plasma SHBG by 45% and 50 mcg of transdermal E₂ increased it by 12%.

Nachtigall LE, Raju U, Banerjee S, Wan L, Levitz M; Serum ESTRADIOL-binding profiles in postmenopausal women undergoing three common estrogen replacement therapies: associations with sex hormone-binding globulin, ESTRADIOL, and estrone levels. Menopause. 2000 Jul-Aug;7(4):243-50.