BMI as a partitioning factor for estradiol and estrone reference intervals in middle-aged men and postmenopausal women.

Abstract

Introduction: Estrogens play a large role in female and male physiology and are routinely determined in the clinical setting. For interpretation, distinct reference intervals are applied for men, pre---, and postmenopausal women. Adipose tissue is a potent producer of estrogens and influences the circulating estrogen concentrations, although its impact on estrogen reference intervals is currently unknown.

Method: We determined estradiol and estrone concentrations in 6,671 middle-aged participants of a large cohort oversampled for persons with BMI >27 kg/m2. We investigated partitioning based on sex, age, menopausal status, and BMI by assessing the proportion of subgroups outside each limit of a shared 95% reference interval (ideally 2.5%) and calculating reference intervals for justified subgroups according to CLSI EP28-A3c.

Results: As expected, the strongest partitioning factor was sex, followed by menopausal status for women. When using a shared reference interval for all BMI categories, 4.9% and 5.2% of values in men with obesity and 11.4% and 7.7% of values in postmenopausal women with obesity fell above the reference interval for estradiol and estrone, respectively. Within postmenopausal women differences in the upper reference limit were found, being 138, 157, and 210 pmol/L for estradiol and 32, 41, and 74 pmol/L for estrone for normal weight, overweight, and obesity, respectively.

Discussion: Laboratory professionals and clinicians should be aware that BMI affects estrogen concentrations to such extent that it may influence clinical interpretation. Ideally their reference intervals should be stratified by BMI category to reflect the increased estrogen concentrations associated with higher BMI.