Menstrual and reproductive factors and risk of vertebral fractures in Japanese women: the Japan Public Health Center-based prospective (JPHC) study

Osteoporos Int. 2018 Dec;29(12):2791-2801. doi: 10.1007/s00198-018-4665-8. Epub 2018 Aug 24.


This large-scale population-based cohort study in Japan was conducted to clarify the effects of menstrual and reproductive factors on the risk of later-life vertebral fractures in women. Significant associations were seen for later menarche, irregular menstruation, and shorter reproductive years, corresponding to the effect of reproductive hormonal disturbance on bone metabolism.

Introduction: This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women.

Methods: Participants were 43,652 women aged 40-69 years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors.

Results: During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16 years [OR (95% CI) = 2.08 (1.24-3.48)] compared to ≤ 13 years and irregular menstruation [1.42 (1.01-2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92-0.99)] in menopausal women. Women with both menarche ≥ 15 years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51-3.73) in all women, 2.25 (1.35-3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499).

Conclusions: Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.

Keywords: Estrogen; Menstrual factors; Reproductive factors; Vertebral fracture; Women.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Anthropometry / methods
  • Female
  • Humans
  • Japan / epidemiology
  • Menopause / physiology
  • Menstruation / physiology*
  • Middle Aged
  • Osteoporotic Fractures / epidemiology
  • Osteoporotic Fractures / etiology*
  • Osteoporotic Fractures / physiopathology
  • Prospective Studies
  • Reproductive History*
  • Risk Factors
  • Spinal Fractures / epidemiology
  • Spinal Fractures / etiology*
  • Spinal Fractures / physiopathology