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Over 30 estrogens have been identified, but only three are measured for use in clinical practice: estradiol, estriol, and estrone. Estradiol is secreted by granulosa cells in developing ovarian follicles. As follicles develop, estradiol levels steadily increase. During a normal menstrual cycle, serum estradiol levels usually peak between 250 and 300 pg/mL, immediately before ovulation occurs.

Estradiol is the most biologically active, naturally occurring estrogen. Both estriol and estrone are metabolites of estradiol. Additionally, estriol forms as the result of conversion of testosterone and estrone. Estrone forms from the conversion of androstenedione, which is synthesized by the adrenal gland.

In premenopausal women, estradiol is the most abundant form of estrogen, whereas in postmenopausal women, estrone is the most abundant. The shift from estradiol to estrone is due to atrophy of the ovaries, which results in the majority of estrogen being produced from the conversion of androstenedione.

A decrease in estradiol levels to less than 20 pg/mL causes loss of its beneficial effects, resulting in decreased calcium resorption, accelerated bone loss and an increase in triglyceride levels and cholesterol/HDL ratio.

Estradiol is measured in women undergoing fertility workups as an indicator of ovarian reserve. Estradiol and FSH are measured on day 2 or 3 of the follicular phase of menstrual cycle, when values are expected to be at their lowest. A high FSH or estradiol level suggests impaired oocyte development. A basal estradiol level of greater than 75 pg/mL has been associated with poor invitro fertilization outcomes.

Aromatase inhibitors are prescribed for postmenopausal women with hormone receptor positive breast cancer. They can reduce estradiol concentration to <1 pg/mL. Patients who do not respond to aromatase inhibitors have estradiol concentrations between 5 and 20 pg/mL.

Estradiol can be measured by immunoassay and liquid chromatography mass spectrometry (LC-MS). The lower limit of quantitation (LLOQ) of immunoassays is 5–30 pg/mL compared to 1–5 pg/mL for LC-MS. Immunoassays are more likely to have interference from drugs such as the estrogen receptor antagonist fulvestrant (Faslodex) and the aromatase inhibitor exemestane. Therefore, LC-MS assays are recommended for measurement of estradiol in populations where low concentrations are expected such as males, postmenopausal females, prepubertal children, and those receiving estrogen suppressing medications or therapies.

Reference ranges are summarized in the following table.


Reference Range


<10 pg/mL


20-75 pg/mL

Females premenopausal

20-400 pg/mL

Females postmenopausal

20-88 pg/mL


Specimen requirement is one red top or SST tube of blood.


Bertelsen BE et al. An ultrasensitive routine LC-MS/MS method for estradiol and estrone in the clinically relevant sub-picomolar range. J Endocr Soc. 2020;4(6):bvaa047.

Nagao T. et al. Serum estradiol should be measured not only during the peri-menopausal period but also the postmenopausal period at the time of aromatase inhibitor administration. World J Surg Oncol 2000;7:88.

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