Osteoporosis International

, Volume 2, Issue 4, pp 180–185 | Cite as

The effects of menopause and estrogen replacement therapy on the renal handling of calcium

  • S. Adami
  • D. Gatti
  • F. Bertoldo
  • M. Rossini
  • A. Fratta-Pasini
  • N. Zamberlan
  • E. Facci
  • V. Lo Cascio
Original Article

Abstract

Mineral metabolism was studied in 99 premenopausal and 80 postmenopausal women both before and after 9–14 months of treatment with 50 µg/day transdermal estradiol. In estrogen-repleted subjects (premenopausal women and postmenopausal women on estrogen replacement therapy) total serum calcium was significantly lower (0.065 mmol/l;p<0.001) than in those who were estrogen-depleted (untreated postmenopausal women). This difference was smaller but still significant for calculated ultrafiltrable calcium (UFCa: 0.02–0.03 mmol/l;p<0.001). However, ionized calcium (both calculated and measured) was not different in the two groups of women. This finding explains why estrogen repletion does not induce changes in the serum level of intact parathyroid hormone (PTH), despite lower total or ultrafiltrable serum calcium. In a parallel study we have shown that intravenous administration of aminobutane bisphosphonate, a powerful inhibitor of bone resorption, produces similar decreases in serum calcium which were associated with significant increases in intact PTH.

Estrogen-depleted women had, on the one hand, significantly higher serum levels of bicarbonate, anion gap, complexed calcium, pH, phosphate and alkaline phosphatase, and higher rates of tubular reabsorption of phosphate and urinary excretion of calcium and hydroxyproline. On the other hand they had lower serum chloride levels and lower rates of tubular reabsorption of calcium.

Altogether these findings might indicate that estrogen deficiency decreases renal sensitivity to PTH. This is responsible for the higher serum phosphate and bicarbonate levels, the resulting mild metabolic alkalosis leading to higher serum levels of complexed ultrafiltrable calcium and higher rates of urinary excretion of calcium, but unchanged serum levels of ionized calcium and PTH.

Keywords

Estrogen replacement therapy Menopause Parathyroid hormone Serum bicarbonate Serum calcium 

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References

  1. 1.
    Lindsay R, Atiken JM, Anderson JB, Hart DM, MacDonald EB, Clarke AC. Long-term prevention of postmenopausal osteoporosis by estrogen: evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1976;1:1038–41.Google Scholar
  2. 2.
    Riggs BL, Melton LJ. Medical progress series: involutional osteoporosis. N Engl J Med 1986;314:1676–86.Google Scholar
  3. 3.
    Nordin BEC, Polley K. Metabolic consequences of the menopause: a cross-sectional, longitudinal and intervention study on 557 normal postmenopausal women. Calcif Tissue Int 1987;41[Suppl 1].Google Scholar
  4. 4.
    Falch JA, Gautvik KM. A longitudinal study of pre- and post-menopausal changes in calcium metabolism. Bone 1988;9:15–9.Google Scholar
  5. 5.
    Prince RL, Dick I, Garcia-Webb P, Retallack RW. The effects of the menopause on calcitriol and parathyroid hormone: response to a low dietary calcium stress test. J Clin Endocrinol Metab 1990;70:1119–23.Google Scholar
  6. 6.
    Marcus R, Madvig P, Young G. Age-related changes in parathyroid hormone and parathyroid hormone action in normal humans. J Clin Endocrinol Metab 1984;58:223–30.Google Scholar
  7. 7.
    Gallagher JC, Riggs BL, Jerpbak CM, Arnaud CD. The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women. J Lab Clin Med 1980;95:373–85.Google Scholar
  8. 8.
    Stevenson JC, Abeyasekera G, Hillyard CJ et al. Calcitonin and the calcium-regulating hormones in postmenopausal women: effect of oestrogens. Lancet 1981;1:693–5.Google Scholar
  9. 9.
    Marshall RW, Selby PL, Chilvers DC, Hodgkinson A. The effect of ethinyloestradiol on calcium and bone metabolism in peri- and postmenopausal women. Horm Metab Res 1984;16:97–9.Google Scholar
  10. 10.
    Selby PL, Peacock M, Barkworth SA, Brown WB, Taylor GA. Early effects of ethinyloestradiol and norethisterone treatment in postmenopausal women on bone resorption and calcium regulating hormone. Clin Sci 1985;69:265–71.Google Scholar
  11. 11.
    Boucher A, D'Amour P, Hamel L, Fugere P, Gascon-Barre M, Lepage R et al. Estrogen replacement decreases the set point of parathyroid hormone stimulation by calcium in normal postmenopausal women. Clin Endocrinol Metab 1989;68:831–6.Google Scholar
  12. 12.
    Packer E, Holloway L, Newhall K, Kanwar G, Butterfield G, Marcus R. Effects of estrogen on daylong circulating calcium, phosphorus, 1,25-dihydroxyvitamin D and parathyroid hormone in postmenopausal women. J Bone Miner Res 1990;5:877–84.Google Scholar
  13. 13.
    Stock JL, Coderre JA, Mallette LE. Effects of a short course of estrogen on mineral metabolism in postmenopausal women. J Clin Endocrinol Metab 1985;61:595–600.Google Scholar
  14. 14.
    Prince RL, MacLughlin Dt, Gaz RD, Neer RM. Lack of evidence for estrogen receptors in human and bovine parathyroid tissue. J Clin Endocrinol Metab 1991;72:1226–8.Google Scholar
  15. 15.
    Adami S, Bolzicco GP, Rizzo A, Salvagno G, Bertoldo F, Rossini M et al. The use of dichloromethylene bisphosphonate and aminobutane bisphosphonate in hypercalcemia of malignancy. Bone Miner 1987;2:395–404.Google Scholar
  16. 16.
    Bijvoet OLM. Measurement of renal handling of phosphate. In: Massry SG, Fleisch H, editors. Renal handling of phosphate. New York and London: Plenum, 1980:1–37.Google Scholar
  17. 17.
    Nordin BEC, Need AG, Hartley TF, Philcox JC, Wilcox M, Thomas DW. Improved method for calculating calcium fractions in plasma: reference values and effect of menopause. Clin Chem 1989;35:14–7.Google Scholar
  18. 18.
    Nussbaum SR, Zahradnik RJ, Lavigne JR et al. Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 1987;33:1364–7.Google Scholar
  19. 19.
    Adami S, Suppi R, Bertoldo F, Rossini M, Residori M, Maresca V et al. Transdermal estradiol in the treatment of postmenopausal bone loss. Bone Miner 1989;7:79–86.Google Scholar
  20. 20.
    Sokoll LJ, Dawson-Hughes B. Effect of menopause and aging on serum total and ionized calcium and protein concentrations. Calcif Tissue Int 1989;44:181–5.Google Scholar
  21. 21.
    Prince RL, Schiff I, Neer RM. Effects of transdermal estrogen replacement on parathyroid hormone secretion. J Clin Endocrinol Metab 1990;71:1284–7.Google Scholar
  22. 22.
    Moore EW. Ionized calcium in normal serum, ultrafiltrates and whole blood determined by ion exchange electrodes. J Clin Invest 1970;49:318–34.Google Scholar
  23. 23.
    Nordin BEC, Need AG, Morris HA, Horowitz M, Robertson WG. Evidence for a renal calcium leak in postmenopausal women. J Clin Endocrinol Metab 1991;72:401–7.Google Scholar
  24. 24.
    Heaney RP. A unified concept of osteoporosis. Am J Med 1965;39:877–80.Google Scholar
  25. 25.
    Jasani C, Nordin BEC, Smith DA, Swanson I. Spinal osteoporosis and the menopause. Proc R Soc Med 1965;58:441–4.Google Scholar
  26. 26.
    Stock JL, Coderre JA, Posillico JT. Effects of estrogen on mineral metabolism in postmenopausal women as evaluated by multiple assays measuring parathyroid hormone bioactivity. J Bone Miner Res 1988;2 [Suppl]:s161.Google Scholar
  27. 27.
    Cheema C, Grant BF, Marcus R. Effects of estrogen on circulating ‘free’ and total 1,25(OH)2 vitamin D and on the parathyroid-vitamin D axis in postmenopausal women. J Clin Invest 1989;83:537–42.Google Scholar
  28. 28.
    Hartwell D, Riis BJ, Christiansen C. Changes in vitamin D metabolism during natural and medical menopause. J Clin Endocrinol Metal 1990;71:127–32.Google Scholar
  29. 29.
    Hagenfeldt Y, Eriksson HA. The estrogen receptor in the rat kidney. Ontogeny, properties and effects of gonadectomy on its concentration. J Steroid Biochem 1988;31:49–56.Google Scholar
  30. 30.
    Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsburg TC et al. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 1988;241:84–6.Google Scholar
  31. 31.
    Cosman F, Shen V, Herrington BS, Seibel M, Ratcliffe A, Lindsay R. Mechanism of estrogen action in osteoporosis treatment assessed by human (1–34)PTH infusion. In: Overgaard K, Christiansen C, editors. Abstracts of the Third International Symposium on Osteoporosis, 1990:astr 368.Google Scholar

Copyright information

© European Foundation for Osteoporosis 1992

Authors and Affiliations

  • S. Adami
    • 1
  • D. Gatti
    • 1
  • F. Bertoldo
    • 1
  • M. Rossini
    • 1
  • A. Fratta-Pasini
    • 1
  • N. Zamberlan
    • 1
  • E. Facci
    • 1
  • V. Lo Cascio
    • 1
  1. 1.Istituto di Semeiotica e Nefrologia MedicaUniversity of VeronaItaly

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