Cyclical changes in calcium metabolism across the menstrual cycle in women with premenstrual dysphoric disorder

J Clin Endocrinol Metab. 2007 Aug;92(8):2952-9. doi: 10.1210/jc.2006-2726. Epub 2007 May 8.


Context: Alterations in calcium homeostasis have long been associated with affective disorders. Recently, it has been suggested that abnormalities in calcium metabolism may be responsible for some affective and somatic symptoms in women with premenstrual syndrome.

Objective: Our objective was to measure fluctuations and group differences in calcium-regulating hormones across the menstrual cycle in women with and without premenstrual dysphoric disorder (PMDD).

Design: We conducted a cross-sectional and prospective study of women with and without PMDD. Participating women underwent 2 months of self-assessment symptom screening and 1 month of hormonal evaluation.

Results: Calcium-regulating hormones varied significantly across the menstrual cycle in both groups. Total serum, ionized and urine calcium, pH, intact PTH, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] varied significantly over the menstrual cycle. The PMDD group, when compared with controls, had significantly lower ionized calcium at phase 1 (menses) (1.166 +/- 0.072 vs. 1.182 +/- 0.087 mmol/liter; P = 0.027), significantly lower urine calcium excretion at three of the five phases (late follicular phase 2, midcycle phase 3, and early luteal phase 4), and significantly lower 1,25(OH)(2)D at luteal phase 4 (45.0 +/- 27.5 vs. 50.6 +/- 33.8 pg/ml; P = 0.032).

Conclusions: Cyclical fluctuations of the calcium-regulating hormones may help us better understand some of the psychological and somatic features of PMDD. The lack of responsiveness in vitamin D metabolism resulting in a decline in 1,25(OH)(2)D during the luteal phase of the menstrual cycle may serve as the biological trigger for the classical features of PMDD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Calcitriol / metabolism
  • Calcium / blood
  • Calcium / metabolism*
  • Calcium / urine
  • Cross-Sectional Studies
  • Estrogens / metabolism
  • Female
  • Homeostasis / physiology
  • Humans
  • Linear Models
  • Luteal Phase / metabolism
  • Menstrual Cycle / metabolism*
  • Parathyroid Hormone / metabolism
  • Premenstrual Syndrome / metabolism*
  • Prospective Studies
  • Vitamin D Deficiency / blood


  • Estrogens
  • Parathyroid Hormone
  • Calcitriol
  • Calcium