Effects of sex and postmenopausal estrogen use on serum phosphorus levels: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 2003-2006.

Background: Elevation of serum phosphorus concentrations has been associated with cardiovascular events in older women and men. Whether age, sex, or estrogen therapy is associated with different phosphorus levels is unknown.

Study Design: Cross-sectional study.

Setting & Participants: 7,005 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2006.

Predictors: Demographic data; body measurement indexes; dietary intake by 24-hour dietary recall and food-frequency questionnaire; data for reproductive health, prescription medication, cardiovascular disease, osteoporosis, and diabetes mellitus obtained by questionnaire; and blood chemistry indexes.

Outcomes & Measurements: Serum phosphorus concentrations.

Results: In both males and premenopausal females, serum phosphorus levels decline progressively with age. In males, the decline continues over the entire age range of 21-85 years. In contrast, in females, serum phosphorus levels increase between ages 46-60 years (sex×age interaction; P<0.001). The increase in serum phosphorus levels in older women is independent of changes in serum parathyroid hormone levels, daily dietary phosphorus intake, and estimated glomerular filtration rate. In analysis of covariance, we show that postmenopausal women receiving estrogen therapy have significantly lower serum phosphorus levels than non-estrogen users after adjusting for age, race, body mass index, daily dietary phosphorus intake, and serum albumin, serum parathyroid hormone, and 25-hydroxyvitamin D levels (3.83 vs 3.98mg/dL; P<0.001).

Limitations: The study was cross-sectional in design and estrogen therapy was not randomly assigned or concealed. Important phosphorus regulatory factors such as serum fibroblast growth factor 23 and klotho were not available in the study.

Conclusions: Estrogen status may account for the difference in serum phosphorus levels in postmenopausal women.