Estradiol (E2)

Estradiol, written E2 and formally 17-beta-estradiol, is the dominant estrogen in humans. Its phenolic A-ring distinguishes it from its androgen precursor and gives it high affinity for the nuclear receptors ER-alpha and ER-beta, while a membrane receptor mediates faster non-genomic effects. In premenopausal women it is made by the two-cell model, LH driving androgen production in theca cells and FSH inducing the granulosa aromatase that converts it; in men and after menopause almost all of it comes from peripheral aromatization in adipose tissue.

Early follicular values sit in the low tens of picograms per millilitre, climb several-fold to a preovulatory peak, fall below about 20 pg/mL after menopause, and in adult men run roughly in the postmenopausal range rather than at zero. Rising preovulatory estradiol is the trigger for the one place in the reproductive axis where feedback turns positive and produces the LH surge. Estradiol is approved for menopausal hormone therapy in oral, transdermal and vaginal forms, and the Women's Health Initiative results from 2002 reshaped how those risks are stated.

Route is not cosmetic: oral estradiol passes through the liver first and raises SHBG and clotting factors, while transdermal delivery largely avoids that. Assay method matters as much, because immunoassays validated in premenopausal ranges lose accuracy at the low concentrations found in men, children and postmenopausal women, where mass spectrometry is the appropriate method.

The recurring error treats estradiol in men as a contaminant to be minimised, when low estradiol is associated with loss of bone density and sexual dysfunction and the evidence for aggressive suppression is thin. The other is reading a single value in a cycling woman as a state variable, when her result can differ several-fold depending only on which day of the cycle the sample was drawn.