Objective: To investigate the protective effect of estrogen on progressive supranuclear palsy (PSP).  

Background: Animal and human epidemiologic studies of Parkinson’s disease and Alzheimer’s dementia have suggested neuroprotective effects of estrogen.

Methods: One-hundred fifty female PSP cases from the ENGENE-PSP study were individually matched by age to 150 female controls. A telephone questionnaire was administered to all study participants to obtain demographic and reproductive characteristics. Information about reproductive characteristics (e.g., age at menarche, age at menopause, hysterectomy status, and use of oral contraceptives and/or estrogen replacement therapy (ERT)) were used to estimate exposure to estrogen. A composite estrogen summary score was derived from reproductive characteristics to distinguish between females with low, medium, and high exposure to estrogen. Conditional logistic regression models were generated to estimate the associations between exogenous and endogenous estrogen exposures and PSP. 

Results: Females who reported never using post-menopausal ERT had nearly twice the odds of PSP than females who reported ever using post-menopausal ERT (aOR=1.92, 95% CI:1.09, 03.37). Similarly, compared to females with the lowest overall exposure to estrogen (score 0), women with higher overall exposure to estrogen had decreased odds of PSP (score 1: aOR=0.52, 95% CI: 0.25 – 1.09; score 2: aOR=0.43, 95% CI: 0.21 – 0.89; score 3: aOR= 0.51, 95% CI: 0.21 – 1.23; p-trend: 0.06). A lagged analysis using reproductive characteristics 10 years prior to PSP symptom onset to generate the estrogen summary score supports these findings. Compared to women with the lowest overall exposure to estrogen, women with higher overall exposure to estrogen had decreased odds of PSP (score 1: aOR=0.37, 95% CI: 0.17 – 0.80; score 2: aOR=0.41, 95% CI: 0.18 – 0.92). 

Conclusions: The results from our case-control study suggest that increased lifetime exposure to estrogen is associated with decreased odds of having PSP. These findings support the neuroprotective effect of estrogen on motor status and cognition in PSP. The neuroprotective role of estrogen in PSP may be related to its anti-inflammatory activity and its effect on the dopaminergic system.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lifetime-exposure-to-estrogen-and-risk-for-progressive-supranuclear-palsy/