Serum phosphate in the general population: a need for sex-specific reference intervals.

Background: Phosphate is important for several metabolic functions and essential for bone mineralization. Sex-differences exist in the relation between serum phosphate and certain diseases. The reference interval for phosphate is age-adjusted in infants, but most institutions use the same intervals for adult men and women despite increasing evidence for age and sex-differences. We aimed to study these differences in two large population-based cohorts in order to evaluate whether current reference intervals are adequate.

Methods: 8837 participants from three cohorts of the Rotterdam Study (RS) and 422,443 participants from UK Biobank (UKBB), aged 40 and older and without chronic kidney disease, were analyzed for sex/differences in serum phosphate using standard reference values (0.8-1.45 mmol or 2.5-4.5 mg/dL). Analyses were further stratified in women by menopausal status.

Results: Women had higher serum phosphate concentrations and a higher population range compared to men in all cohorts. Hypophosphatemia was more prevalent in men and hyperphosphatemia was more prevalent in women. Sex-differences were present in all age-categories. Perimenopausal women had higher serum phosphate concentrations than men of the same age, but lower than postmenopausal women of the same age.

Conclusions: This study in two population-based cohorts showed that women have higher serum phosphate concentrations than men and that women show a marked increase in serum phosphate during menopause. Moreover, the population range for serum phosphate was higher in women than in men. These findings indicate a need for sex-specific reference intervals for serum phosphate in adults older than 45 years.