Depression rates are higher in women, especially during periods of hormonal fluctuation. Reproductive system disorders (RSDs), which often disrupt hormonal balance, may contribute to this mental health burden. Despite their prevalence and significant health implications, the link between RSDs and depression remains underexplored, leaving a gap in understanding these women’s mental health risks.

Using Danish nationwide health registers (2005–2018), we conducted a cohort study of 2,295,824 women aged 15–49, examining depression outcomes in 265,891 women diagnosed with 24 RSDs, including endometriosis, polycystic ovary syndrome, and pain-related diagnoses. For each RSD, age-matched controls were selected. We calculated incidence rates, incidence rate ratios, and prevalence proportions of depression diagnoses or antidepressant use around RSD diagnosis.

Across all RSD subtypes, women demonstrated higher rates of depression both before and after diagnosis, with a peak within the year following diagnosis. Incidence rate ratios within 1 year of RSD diagnosis ranged from 1.15 (95% confidence interval [CI] 1.06–1.25) to 2.09 (95% CI 1.98–2.21), depending on RSD subtype. Elevated depression prevalence was observed 3 years before diagnosis, suggesting mental health impacts may have preceded clinical RSD identification.

This study reveals a striking association between RSDs and depression. Women with RSDs are more likely to suffer from depression, before and after RSD diagnosis, highlighting the need for integrated mental health screening and intervention. With over 10% of women affected by RSDs, addressing this overlooked mental health burden is imperative for improving well-being in a significant portion of the population.