A two sample Mendelian randomized study of the association of sex hormones and behavioral and clinical risk factors with macular hole

Macular hole (MH) is a disease of the vitreoretinal interface that develops in relation to age and gender, and is 3.3 times more prevalent in females than in males. However, it remains inconclusive whether gender plays a role in the pathogenesis of MH. We adopted a two-sample Mendelian randomisation (MR) analysis to explore the relationship between free testosterone, bioavailable testosterone, oestradiol, menopause, smoking, alcohol consumption, type 2 diabetes, diastolic blood pressure, and systolic blood pressure and the risk of MH. We found that genetically predicted free testosterone levels in males were significantly associated with an increased risk of MH (IVW model: OR = 1.642; 95% CI, 1.162-2.322; P = 0.005), while genetically predicted oestradiol levels in females were significantly associated with a reduced risk of MH (IVW model: OR = 0.711; 95% CI, 0.517-0.978; P = 0.036). A sensitivity analysis verified the robustness of the causal relationship. MVMR results indicate that oestradiol in females is associated with MH risk using the IVW method (OR = 0.66; 95% CI, 0.47-0.88; P = 0.011). Our study demonstrates that the genetic risk of free testosterone in males and oestradiol in females may be correlated with MH risk.