Association of Female Reproductive Factors with Incidence of Fracture among Postmenopausal Women in Korea

Importance: Although estrogen level is positively associated with bone mineral density, there are limited data on the risk of fractures after menopause. Objective: To investigate whether female reproductive factors are associated with fractures among postmenopausal women. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Korean National Health Insurance Service database on 1272115 postmenopausal women without previous fracture who underwent both cardiovascular and breast and/or cervical cancer screening from January 1 to December 31, 2009. Outcome data were obtained through December 31, 2018. Exposures: Information was obtained about reproductive factors (age at menarche, age at menopause, parity, breastfeeding, and exogenous hormone use) by self-administered questionnaire. Main Outcomes and Measures: Incidence of any fractures and site-specific fractures (vertebral, hip, and others). Results: Among the 1272115 participants, mean (SD) age was 61.0 (8.1) years. Compared with earlier age at menarche (≤12 years), later age at menarche (≥17 years) was associated with a higher risk of any fracture (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.17-1.31) and vertebral fracture (aHR, 1.42; 95% CI, 1.28-1.58). Compared with earlier age at menopause (<40 years), later age at menopause (≥55 years) was associated with a lower risk of any fracture (aHR, 0.89; 95% CI, 0.86-0.93), vertebral fracture (aHR, 0.77; 95% CI, 0.73-0.81), and hip fracture (aHR, 0.88; 95% CI, 0.78-1.00). Longer reproductive span (≥40 years) was associated with lower risk of fractures compared with shorter reproductive span (<30 years) (any fracture: aHR, 0.86; 95% CI, 0.84-0.88; vertebral fracture: aHR, 0.73; 95% CI, 0.71-0.76; and hip fracture: aHR, 0.87; 95% CI, 0.80-0.95). Parous women had a lower risk of any fracture than nulliparous women (aHR, 0.96; 95% CI, 0.92-0.99). Although breastfeeding for 12 months or longer was associated with a higher risk of any fractures (aHR, 1.05; 95% CI, 1.03-1.08) and vertebral fractures (aHR, 1.22; 95% CI, 1.17-1.27), it was associated with a lower risk of hip fracture (aHR, 0.84; 95% CI, 0.76-0.93). Hormone therapy for 5 years or longer was associated with lower risk of any factures (aHR, 0.85; 95% CI, 0.83-0.88), while use of oral contraceptives for 1 year or longer was associated with a higher risk of any fractures (aHR, 1.03; 95% CI, 1.01-1.05). Conclusions and Relevance: The findings of this cohort study suggest that female reproductive factors are independent risk factors for fracture, with a higher risk associated with shorter lifetime endogenous estrogen exposure. Interventions to reduce fracture risk may be needed for women at high risk, including those without osteoporosis..