RELIABILITY OF MEASUREMENTS OF TOTAL, PROTEIN-BOUND, AND UNBOUND ESTRADIOL IN SERUM

Estradiol (E(2)) circulates in the blood in three states: unbound (U-E (2)), bound to sex-hormone binding globulin (SHBG-E(2)), and bound to albumin. There is evidence to support the concept that only U-E(2) and albumin-bound E(2), are bioavailable (i.e., rapidly extracted by tiss ues). A case-control study nested within a large cohort of women, in w hich we are examining the effect of estrogens on breast cancer risk, o ffered the opportunity to assess the reliability of measurements of E( 2), the percentage of SHBG-E(2), and the percentage of U-E(2) based on multiple annual serum specimens. Long-term (1-2 year) reliability, as estimated by the intraclass correlation coefficient, was assessed in a subgroup of 71 premenopausal and 77 postmenopausal controls for whom two or three serum specimens were assayed. In postmenopausal women th e intraclass correlation coefficient for a single measurement of total E(2) was only 0.51. As for the percentage of SHBG-E(2), intraclass co rrelation coefficients were 0.83 and 0.94, and for U-E(2), 0.72 and 0. 77 in the premenopausal and postmenopausal groups, respectively. These data suggest that, whereas single determinations of total E(2) are in sufficient to reliably estimate a woman's true mean level, a single me asurement of the percentage of SHBG-E(2) or U-E(2) is adequate to asse ss bioavailability of E(2) in an epidemiological study, irrespective o f day of the menstrual cycle.