Abstract
BACKGROUND: The higher prevalence of depression and anxiety among women attracted widespread attention. However, investigations into the underlying etiology remained insufficient. This study aimed to investigate associations between female reproductive factors and the risk of depression and anxiety.
METHODS: 249,140 female participants of the UK Biobank were included in this study. We used multivariate Cox proportional hazard models to investigate the associations. Multiple adjusted restricted cubic splines were constructed to assess the shape of continuous reproductive factors associated with depression and anxiety risk.
RESULTS: During a median follow-up of 13.6 years, 10,173 (4.08 %) participants developed depression, and 10,246 (4.11 %) participants developed anxiety. Four or more pregnancies (HR = 1.27, 95 % CI 1.19-1.35; HR = 1.15, 95 % CI 1.08-1.22), one stillbirth (1.31, 1.15-1.49; 1.21, 1.05-1.38), two or more spontaneous miscarriages (1.39, 1.27-1.51; 1.19, 1.09-1.30), and two or more pregnancy terminations (1.31, 1.17-1.47; 1.44, 1.28-1.62) independently predicted elevated risks of depression and anxiety. Meanwhile, age at first birth <20 (1.22, 1.14-1.32; 1.18, 1.09-1.27), age at menarche <12 (1.11, 1.05-1.17; 1.08, 1.02-1.14), age at menopause <45 (1.26, 1.16-1.37; 1.22, 1.12-1.32), hysterectomy (1.48, 1.41-1.56; 1.29, 1.22-1.36), and oophorectomy (1.43, 1.33-1.54; 1.20, 1.11-1.29) were also linked to increased risks of depression and anxiety, respectively. Notably, later menarche >15 years exhibited a unique association with depression risk (1.17, 1.07-1.29), but not anxiety.
CONCLUSIONS: In this study, some reproductive factors were associated with incident depression and anxiety in middle-aged and older women, suggesting the necessity of incorporating key reproductive history into routine screening for mental disorders in women.