Evaluation of the two-way associations between mental disorders and menstrual irregularities: A Mendelian randomization study from both directions

Abstract

Objective

We aimed to assess the bidirectional relationship between mental disorders and menstrual irregularities using a two-sample Mendelian randomization (MR) approach.

Methods

The analyses were conducted using a two-sample MR method. Analytical tools were derived from large-scale genome-wide association studies, including those on schizophrenia (SCZ, n = 127,906), bipolar disorder (BIP, n = 353,899), major depressive disorder (MDD, n = 674,452), anxiety and stress-related disorder (ASRD, n = 1,096,458), irregular menses (n = 196,550), excessive menstruation (n = 144,388), and dysmenorrhea (n = 114,540). Inverse variance weighting was used for the two-sample MR analyses, while sensitivity analyses were performed using MR-Egger, weighted median, and simple median methods.

Results

MDD and ASRD were associated with an increased risk of irregular menses (P < 0.05); however, no reliable outcomes were found regarding the relationship between SCZ, BIP, and the three types of menstrual irregularities (P > 0.05). Furthermore, ASRD was also associated with an increased likelihood of excessive menstruation and dysmenorrhea (P < 0.05). However, the relationship between MDD and excessive menstruation was not statistically significant (P > 0.05). Dysmenorrhea was associated with an increased risk of MDD and ASRD (P < 0.05).

Conclusion

This study provides strong evidence supporting the associations between ASRD and the three types of menstrual irregularities, as well as between MDD and irregular menses and dysmenorrhea.