Relation of sex and estrogen therapy to serum fibroblast growth factor 23, serum phosphorus, and urine phosphorus: the Heart and Soul Study

Am J Kidney Dis. 2011 Nov;58(5):737-45. doi: 10.1053/j.ajkd.2011.06.011. Epub 2011 Aug 19.


Background: Menopause is associated with urine phosphorus retention, which is mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone originating from bone that regulates urine phosphorus excretion. Whether sex or estrogen therapy is associated with different FGF-23 levels is unknown.

Study design & setting: Cross-sectional study of ambulatory individuals with prevalent cardiovascular disease.

Predictors: Sex and, in women, use or nonuse of estrogen.

Outcomes: Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to glomerular filtration rate (TMP/GFR), and plasma FGF-23 concentrations.

Results: For 987 participants, mean age was 67 ± 11 years, 182 (18%) were women, and 46 (25%) were using estrogen. Mean estimated GFR was 71 ± 23 (SD) mL/min/1.73 m(2). Compared with women who were not using estrogen, both women on estrogen therapy and men had significantly lower serum phosphorus concentrations, lower TMP/GFR values (indicating higher urine phosphorus excretion), and lower FGF-23 concentrations with adjustment for age, demographics, and kidney function (P < 0.001 for each). Mean FGF-23 levels were 68.7 (95% CI, 59.7-79.0) relative units (RU)/mL in non-estrogen-using women, 43.8 (95% CI, 41.2-46.5) RU/mL in men, and 45.1 (95% CI, 35.2-57.4) RU/mL in women using estrogen in adjusted analysis (P < 0.001).

Limitations: Most participants were men. Estrogen therapy was not randomly assigned.

Conclusions: Older women who are not using estrogen have higher FGF-23 levels than either men or women using estrogen. In the context of prior literature, these data suggest that postmenopausal phosphorus retention may stimulate higher FGF-23 concentrations after menopause.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / urine
  • Cross-Sectional Studies
  • Estrogen Replacement Therapy*
  • Female
  • Fibroblast Growth Factors / blood*
  • Humans
  • Male
  • Phosphorus / blood*
  • Phosphorus / urine*
  • Sex Factors


  • Phosphorus
  • Fibroblast Growth Factors
  • fibroblast growth factor 23