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Estradiol is the primary sex hormone in females, required for sexual development and maintenance of reproductive health.
In females, this steroid hormone is produced primarily by the ovaries but also in other tissues including body fat, liver, adrenal, and breast tissues.
Once released into the blood, estradiol binds to a protein called sex hormone-binding globulin (SHBG). Small amounts of the hormone also bind to the protein albumin. The majority of circulating estradiol is therefore protein-bound in the plasma and only 2.21% (+/- 0.04%) exists as free or active estradiol. The level of unbound estradiol remains the same throughout the female’s menstrual cycle.
The free estradiol is deactivated when it undergoes metabolism in the liver. This includes conversion to the less active estrogens, estrone and estriol. Of these, estriol is the main estrogen metabolite found in the urine. In the liver, estradiol undergoes conjugation by sulfate and glucorinide. This conjugated hormone is then excreted via the kidneys.
Estradiol taken in tablet form is not readily absorbed in the gut and may immediately be taken up and broken down by the liver instead via a mechanism referred to as first pass metabolism. This can lead to diminished effects of the estradiol and can also cause side effects. To bypass the liver, the skin (transdermal) and vaginal routes of administration are used to deliver estradiol to the body.