After menopause, estradiol (E₂) is predominately an intracrine hormone circulating in very low serum concentrations.

The objective of this work is to examine determinants of E₂ concentrations in women beyond age 70 years.

A cross-sectional, community-based study was conducted.

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.

Sex steroids were measured by liquid chromatography–tandem mass spectrometry. Values below the limit of detection (LOD; E₂ 11 pmol/L [3 pg/mL] were assigned a value of LOD/√2 to estimate total E_2.

E₂ and estrone (E₁) were below the LOD in 66.1% and 0.9% of women, respectively. The median (interdecile ranges) for E₁ and detectable E₂ 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 E₂ vs detectable E₂ were older (median age 74.1 years vs 73.8, P = .02), leaner (median body mass index [BMI] 26.8 kg/m² vs 28.5, P < .001), and had lower E₁, testosterone and DHEA concentrations (P < .001). A linear regression model, including age, BMI, E₁, and testosterone, explained 20.9% of the variation in total E₂, but explained only an additional 1.2% of variation over E₁ alone. E₁ and testosterone made significant contributions (r² = 0.162, P < .001) in a model for the subset of women with detectable E₂.

Our findings support E₁ as a principal circulating estrogen and demonstrate a robust association between E₁ and E₂ concentrations in postmenopausal women. Taken together with prior evidence for associations between E₁ and health outcomes, E₁ should be included in studies examining associations between estrogen levels and health outcomes in postmenopausal women.