• Liang Pang, Kai Wu, Pingping Su, Zhicheng Liao, and Cunxian Lv.
• Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, China.
• Medicine (Baltimore). 2025 Jan 31; 104 (5): e41362e41362.

AbstractEpidemiology shows women have a higher incidence of osteoarthritis (OA) than men. However, there is not enough evidence to suggest a direct correlation between female reproductive factors and OA. Therefore, this study will employ Mendelian randomization (MR) analysis to investigate whether there is a causal relationship between the 2. This study used a 2-sample MR analysis with single nucleotide polymorphisms significantly associated with female reproductive factors as instrumental variables (IV). We used inverse variance weighted (IVW), MR-Egger regression, weighted median method to infer a causal relationship between female reproductive factors and OA, Cochran Q heterogeneity test by IVW and MR-Egger method, MR PRESSO method and IVW-radial method to detect outliers, MR_pleiotropy_test function and MR PRESSO method for multivariate validity test, and calculation of F-value was used to assess the presence of weak IVs. Finally, the stability of the findings was assessed using the leave-one-out method. Our research shows that there is no reliable causal relationship between an increase in Age at menarche (years) (AAM) and Age at menopause (years) (AM) and OA, that an increase in Age first had sexual intercourse (years) (AFS) is associated with a decreased risk of knee OA and/or hip OA and hand OA, that an increase in Age at first live birth (years) (AFB) is associated with a decreased risk of knee OA and/or hip OA and knee OA, and that an increase in Number of live births (NOB) is associated with an increased risk of knee OA and/or hip OA. This study provides genetic support for an increase in AFS as a reduced knee OA and/or hip OA and hand OA risk factor, an increase in AFB as a reduced knee OA and/or hip OA and knee OA risk factor, and an increase in NOB as an increased knee OA and/or hip OA risk factor. Further studies are needed to elucidate the potential mechanisms underlying the causal associations between AFS, AFB, and NOB and site-specific OA.Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.

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