In plasma, estradiol is largely bound to sex hormone-binding globulin, also to albumin. Only a fraction of 2.21% (+/- 0.04%) is free and biologically active, the percentage remaining constant throughout the menstrual cycle.
Deactivation includes conversion to less-active estrogens such as estrone and estriol. Estriol is the major urinary metabolite. Estradiol is conjugated in the liver by sulfate and glucuronide formation and, as such, excreted via the kidneys.
Some of the water-soluble conjugates are excreted via the bile duct, and partly reabsorbed after hydrolysis from the intestinal tract. This enterohepatic circulation contributes to maintaining estradiol levels.
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