Obstructive Sleep Apnea and Female Reproductive Endocrine Diseases: A Mendelian Randomization and Mediation Analysis.

OBJECTIVE

This study aimed to evaluate the potential causal association between obstructive sleep apnea (OSA) and the risk of female reproductive endocrine diseases (REDs), including polycystic ovary syndrome (PCOS), endometriosis (EMs), and female infertility (FI) using Mendelian randomization (MR) analysis.

METHODS

Genome-wide association study (GWAS) summary statistics were obtained from the FinnGen consortium, GWAS catalog, UK Biobank, and GIANT consortium, with a focus on individuals of European ancestry. Single-nucleotide polymorphisms (SNPs) correlated with OSA were investigated in relation to REDs (PCOS, EMs, and FI) using the inverse-variance weighted (IVW) method. Sensitivity analyses were used to test the consistency of the results. Furthermore, a two-step MR was performed to quantify the proportion of the effect of body mass index (BMI)-mediated OSA on REDs.

RESULTS

Our primary MR analysis revealed that genetically predicted OSA was positively linked to increased PCOS (odds ratio [OR] 1.341, 95% confidence interval [CI] 1.014-1.774, p = 0.039), while no significant causal relationships were observed between OSA and EMs, or FI (all p > 0.05). Mediation analysis showed that BMI mediated 18% of the association between OSA and PCOS (OR = 1.053, 95% CI = 1.015-1.105).

CONCLUSION

This study suggested that early detection and management of OSA in women may be a new strategy to improve PCOS in the future. Meanwhile, it also emphasized the importance of adjusting BMI as a therapeutic strategy to mitigate the effects of OSA on PCOS.