Objective: To evaluate the association between markers of lifetime estrogen exposure and Parkinson’s Disease (PD) in a large digital cohort of postmenopausal women.

Background: The lower prevalence of PD in women has long been partly attributed to a potential neuroprotective role of estrogen. Mouse model studies have demonstrated a protective effect of estrogen against dopamine depletion induced by neurotoxic agents, and epidemiological studies from the early 2000s demonstrated a lower PD prevalence and later age of onset with longer estrogen exposure. However, many of these studies are now more than a decade old and were conducted in relatively small and homogenous cohorts. Large, diverse digital databases, such as Fox Insight, provide an opportunity to revisit this question in contemporary populations.

Method: Data used in the preparation of this presentation were obtained from the large Fox Insight online database of self-reported health information from individuals with PD and healthy controls(https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp), on 28/02/2026. Variables related to PD, sociodemographics, and reproductive history were extracted specifically from women who identified as postmenopausal.  For this analysis, entries with missing or implausible reproductive history were excluded (320 PD cases, 44 controls). Multivariable logistic regression models evaluated associations between markers of estrogen exposure and PD status, adjusting for age.

Results: A total of 1,113 women were included (915 PD cases, 198 controls). Mean age was 65.45± 7.39 years in cases and 61.96 ± 7.78 years in controls (p <0.001). In age-adjusted logistic regression, reproductive lifespan (OR 0.99, 95% CI 0.97–1.01, p=0.44), early menopause (OR 0.86, 95% CI 0.61–1.23, p=0.45), natural versus surgical menopause (OR=0.95, CI 0.69-1.33 P=0.77), and number of pregnancies (OR 0.98, 95% CI 0.90–1.08, p=0.73) were not associated with PD. Stratified analysis by reproductive lifespan quartiles similarly showed no significant association (p > 0.05). Age remained a strong predictor of PD (OR=1.06 per year, p<0.001).

Conclusion: In this large online cohort of postmenopausal women, markers associated with lifetime estrogen exposure were not significantly associated with PD, suggesting that the neuroprotective effects of estrogen still remains under question.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/revisiting-the-association-between-estrogen-exposure-and-parkinsons-disease-a-fox-insight-analysis/