Abstract
BACKGROUND: Although endogenous estrogen exposure, influenced by reproductive factors (RFs), is negatively associated with fracture risk, there is limited and conflicting information on the association between these factors and the incidence of fractures. This study aimed to evaluate the association between RFs and fracture incidence (FXI) separately. METHODS: This longitudinal study commenced in 1999 and concluded in 2021. It is performed on women without previous fractures and adjusted for confounders. RFs, including age at menarche, parity, abortion, duration of breastfeeding (BF), hormonal contraceptive use, and age at menopause, were exposure variables. The incidence of fractures was the primary outcome. A Cox proportional hazards regression model was used to estimate the associations between RFs and FXI outcomes. RESULTS: The median (interquartile range) of follow-up time was 15.0 (12.1-17.0) years. A total of 19.9% (1324/6653)of the women were menopausal at baseline, and 13% (865/6653) of the remaining participants reached menopause at the end of follow-up. At the end of the follow-up, 222 (3.3%) participants had fractures. The mean age of participants at the initiation of the study and last follow-up were 35.8 (15.5) and 50.0 (15.3) years, respectively. After adjusting for potential confounders, the HR of FXI increased by 10% per one extra delivery (HR: 1.10,95% CI: (1.03, 1.18); p = 0.01), and by 12% per one-year increase in age at menarche (HR: 1.12, 95% CI: (1.02, 1.23); p = 0.02). The HR of FXI decreased by 3% per month extra exclusive BF (HR: 0.97,95% CI: (0.94, 0.99); p = 0.04). CONCLUSIONS: The results elucidate that a longer duration of exclusive BF has a protective effect on FXI. In contrast, increasing age at menarche and the number of parities increase the risk of FXI.