Objectives: Estrogen not only plays a key role in the decreased risk of Parkinson's disease (PD) but also influences its severity. We aimed to explore the effect of the reproductive lifespan on the motor progression of PD female patients in a large prospective cohort study.
Methods: A competing risk analysis with a Fine and Gray model on 491 female and 609 male patients with PD was conducted. We regarded the chance of faster motor progression (as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) III increasing by ≥16 points during follow-up) and the chance of death as competing risks. The reproductive lifespan was regarded as the variable of interest, while faster motor progression was set as the primary outcome.
Results: In the multivariable competing risk analysis, the male sex was not significantly associated with faster motor progression (subdistribution hazard ratio (SHR) 0.888, 95% CI 0.652-1.209, p = 0.450), while a shorter reproductive lifespan was associated with faster motor progression in women (SHR 0.964, 95% CI 0.936-0.994, p = 0.019). Sensitivity analysis indicated that a shorter reproductive lifespan was also significantly associated with faster motor progression in the 48 female patients who reported menopause after the onset of PD (SHR 0.156, 95% CI 0.045-0.542, p = 0.003). A linear mixed model also revealed the significant main effects of a short reproductive lifespan on the higher UPDRS III score in PD female patients at the last visit (p = 0.026).
Conclusions: Our study indicates that a short reproductive lifespan contributes to faster motor progression in PD female patients, which has important implications for understanding the role of endogenous estrogen exposure in female PD and is beneficial to select appropriate patients in clinical trials.
Keywords: Parkinson’s disease; estrogen; motor progression; reproductive factors; sex difference.