Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition

J Bone Miner Res. 2011 Apr;26(4):840-9. doi: 10.1002/jbmr.259.


The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We analyzed data from 2283 participants of the Study of Women's Health Across the Nation, a longitudinal community-based cohort study of women aged 42 to 52 years at baseline. At baseline and annually through follow-up visit 8, participants provided questionnaire data, urine samples, serum samples, and anthropometric measurements. Using multivariable repeated-measures mixed models, we examined associations between annually assessed VMS frequency and annual NTX measurements. Our results show that mean adjusted NTX was 1.94 nM of bone collagen equivalents (BCE)/mM of creatinine higher among early perimenopausal women with any VMS than among early perimenopausal women with no VMS (p < .0001). Mean adjusted NTX was 2.44 nM BCE/mM of creatinine higher among late perimenopausal women with any VMS than among late perimenopausal women with no VMS (p = .03). Among premenopausal women, VMS frequency was not significantly associated with NTX level. When NTX values among women with frequent VMS (≥6 days in past 2 weeks) were expressed as percentages of NTX values among women without frequent VMS, the differences were 3% for premenopausal women, 9% for early perimenopausal women, 7% for late perimenopausal women, and 4% for postmenopausal women. Adjustment for serum follicle-stimulating hormone (FSH) level greatly reduced the magnitudes of associations between VMS and NTX level. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Biomarkers
  • Bone Remodeling / physiology*
  • Calcium, Dietary / therapeutic use
  • Collagen Type I / blood
  • Estradiol / blood
  • Ethnicity / statistics & numerical data
  • Female
  • Follicle Stimulating Hormone / blood
  • Hot Flashes / epidemiology
  • Humans
  • Longitudinal Studies
  • Menopause / blood
  • Menopause / physiology*
  • Middle Aged
  • Peptides / blood
  • Perimenopause / blood
  • Perimenopause / physiology
  • Postmenopause / blood
  • Postmenopause / physiology
  • Premenopause / blood
  • Premenopause / physiology
  • Racial Groups / statistics & numerical data
  • Smoking / epidemiology
  • Sweating
  • United States
  • Vasomotor System / physiopathology*
  • Vitamin D / therapeutic use


  • Biomarkers
  • Calcium, Dietary
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Vitamin D
  • Estradiol
  • Follicle Stimulating Hormone