Female reproductive factors and the risk of Parkinson’s disease: a nationwide cohort study

There are conflicting finds in the literature regarding the association of female estrogen status and the incidence of Parkinson's disease (PD). We aimed to investigate whether female reproductive factors are associated with PD. Using the Korean National Health Insurance System database, 4,729,546 postmenopausal women without PD were identified. The new incidence of PD was defined as subjects with an ICD-10 code for PD (G20) and with a rare intractable disease registration code for PD (V124). The Cox proportional hazard models were used to evaluate the associations of various reproductive factors with incidence of PD. During the median follow-up of 5.84 years, 20,816 individuals were diagnosed with PD. An increased risk of PD was observed in subjects with a later age at menarche (≥ 17 years) compared with reference subjects (13 years ≤ age at menarche ≤ 14 years) (adjusted hazard ratio, aHR 1.10, 95% confidence interval, CI 1.05-1.16). As age at menopause increased, risk of PD decreased (P for trend 0.019). Consistently, decreased risk of PD was observed (aHR 0.91, 95% CI 0.85-0.96) in subjects with longer duration of fertility (≥ 40 years of age) compared with shorter duration of fertility (< 30 years of age). Hormone replacement therapy and oral contraceptives independently increased the risk of PD by 17% and 7%, respectively. Female reproductive factors are independent risk factors for PD, with higher risk associated with shorter lifetime exposure to endogenous estrogen.