According to the Global Burden of Disease 2021, depression and anxiety ranked as the two most prevalent mental health conditions globally, affecting over 300 million individuals worldwide, including more than 200 million women, and the annual incidence rate of these disorders has shown a continuous upward trend (“Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021,” 2024). Depressive disorders and anxiety disorders not only impair daily functioning and social interactions, but are also associated with increased risks of morbidity and mortality from chronic non-communicable diseases, such as cardiovascular disease, diabetes, and hypertension (Carney and Freedland, 2017; Katon, 2003; Roest et al., 2010; Scott et al., 2016; Seldenrijk et al., 2015). With the rising global disease burden of depression and anxiety disorders, investigations into the underlying etiology, especially risk factors for higher prevalence in women, have attracted widely concerns.

The pronounced gender disparity in mental disorders emerged during adolescence and persisted through midlife, coinciding with women's reproductive lifespan (Kessler et al., 1993). Previous studies demonstrated that the high prevalence of depression and anxiety in women was multifactorially determined, involving genetic predisposition, sociocultural determinants, maladaptive coping mechanisms, adverse childhood experiences, and exposure to sexual violence (Anyan and Hjemdal, 2018; Hankin and Abramson, 1999; Karger, 2014; Kessler et al., 1993; Kuehner, 2003; Kullberg et al., 2020; Noble, 2005; Oldehinkel and Bouma, 2011; Ruble et al., 1993; Zheng et al., 2023). Furthermore, robust epidemiological data established significant associations between some female-specific reproductive factors, particularly pregnancy loss, surgical interventions, age at menarche/menopause, age at first birth, and timing of first sexual intercourse and risk of subsequent mental health disorders (Broen et al., 2006; Deng et al., 2011; He et al., 2019; Hu et al., 2024; Kim et al., 2023; McNestry et al., 2023; Ohi et al., 2022; Rocca et al., 2018; Tondo et al., 2017; Westby et al., 2021; Wilson et al., 2018), pointing to the significant role of female reproductive factors in the development of depression or anxiety.

However, there remained a lack of systematic, large-sample prospective study on the association between some female-specific factors and depression and anxiety in adulthood. This large-scale prospective cohort study utilizing UK Biobank data investigated the relationships between female-specific reproductive factors (pregnancy, stillbirth, spontaneous abortion, pregnancy termination, age at first birth, menarche, menopause, hysterectomy, and oophorectomy) during puberty, childbearing, and menopausal stages, and the incidence of depression and anxiety in middle-aged and older women aged 40–69 years.