Estrone Is a Strong Predictor of Circulating Estradiol in Women Age 70 Years and Older

Importance: After menopause, estradiol (E-2) is predominately an intracrine hormone circulating in very low serum concentrations. Objective: The objective of this work is to examine determinants of E-2 concentrations in women beyond age 70 years. Design and Setting: A cross-sectional, community-based study was conducted. Participants: A total of 5325 women participated, with a mean age of 75.1 years (+/- 4.2 years) and not using any sex steroid, antiandrogen/estrogen, glucocorticoid, or antiglycemic therapy. Main Outcome Measures: Sex steroids were measured by liquid chromatography-tandem mass spectrometry. Values below the limit of detection (LOD; E-2 11 pmol/L [3 pg/mL] were assigned a value of LOD/root 2 to estimate total E-2. Results: E-2 and estrone (E-1) were below the LOD in 66.1% and 0.9% of women, respectively. The median (interdecile ranges) for E-1 and detectable E-2 were 181.2 pmol/L (range, 88.7-347.6 pmol/L) and 22.0 pmol/L (range, 11.0-58.7 pmol/L). Women with undetectable E-2 vs detectable E-2 were older (median age 74.1 years vs 73.8, P =.02), leaner (median body mass index [BMI] 26.8 kg/m(2) vs 28.5, P <.001), and had lower E-1, testosterone and DHEA concentrations (P <.001). A linear regression model, including age, BMI, E-1, and testosterone, explained 20.9% of the variation in total E-2, but explained only an additional 1.2% of variation over E-1 alone. E-1 and testosterone made significant contributions (r(2) = 0.162, P <.001) in a model for the subset of women with detectable E-2. Conclusions: Our findings support E-1 as a principal circulating estrogen and demonstrate a robust association between E-1 and E-2 concentrations in postmenopausal women. Taken together with prior evidence for associations between E and health outcomes, E1- should be included in studies examining associations between estrogen levels and health outcomes in postmenopausal women.