Jung Eun Yoo1, Dong Wook Shin2,3, Kyungdo Han4, Dahye Kim5, Ji Won Yoon6, Dong-Yun Lee7. 1. Healthcare System Gangnam Center, Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 2. Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 3. Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea. 4. Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea. 5. Department of Medical Statistics, The Catholic University of Korea, Seoul, Republic of Korea. 6. Healthcare System Gangnam Center, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 7. Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Abstract
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 1 272 115 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 1 272 115 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.
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 1 272 115 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 1 272 115 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.
Authors: Sungsoon Hwang; Se Woong Kang; Kyung Jun Choi; Ki Young Son; Dong Hui Lim; Dong Wook Shin; DooSeok Choi; Sang Jin Kim Journal: Sci Rep Date: 2022-04-12 Impact factor: 4.379