There are many questions which cannot be answered without a very sensitive
estradiol assay. A recombinant cell bioassay (RCBA) for
estradiol was developed in 1994. The sensitivity of the bioassay is 0.02-0.2 pg/ml (0.07-0.7 pmol/L), more than 20 times more sensitive than commercial RIAs and 10 times more sensitive than newer mass spectrometry assays. The RCBA for
estradiol opened the door to study low levels of
estradiol equivalents (EE) across the physiological spectrum of life from prepubertal children through menopause and across the spectrum from normal physiology, in boys as well as girls, to pathology, including: premature thelarche;
estradiol suppression in children treated with
GnRH analogues for
precocious puberty;
aromatase inhibition in boys with
growth hormone deficiency; the differences between oral and transdermal routes of
estrogen administration in girls with
Turner's syndrome; women with
breast cancer treated with
aromatase inhibitors; and women with urogenital
atrophy treated with low dose vaginal
estrogen. A bioassay also allows study of
endocrine disruptors, like
phytoestrogens and other environmental compounds, which are relevant to public health and
alternative medicine options. This paper reviews the assay and the last 20 years of applications. A bioassay for
estrogen has a role because measuring biological effect is theoretically useful, increasing the understanding of physiology in addition to biochemical levels, giving different information than other assays, and opening the door to measure very low levels of
estrogen activity in both humans and the environment.