Lifetime exposure to estrogens and Parkinson's disease in California teachers

Parkinson's disease (PD) is consistently observed to occur less frequently in women than men, prompting investigation into whether estrogen protects against neurodegeneration of dopaminergic neurons.

We used baseline data in the California Teachers Study, a prospective cohort of women, to investigate whether reproductive factors indicating higher long-term estrogen levels are associated with PD using a nested case-control approach. We identified 228 PD cases and 3349 unaffected controls frequency matched by age and race.

Women who reported using combined estrogen/progesterone therapy or progesterone only formulations had a 57% increase in PD risk (OR = 1.57, 95% CI = 1.06, 2.34) compared to never having used HT. Compared to women with menopause at 50-52 years, menopause at younger (<35-46 years: OR = 0.59, 95% CI = 0.37, 0.94) and older ages (≥53 years: OR = 0.54, 95% CI = 0.36, 0.83) had lower PD risk. A derived composite estrogen summary score for women's exposure to both endogenous and exogenous estrogens throughout life indicated that women with presumed higher cumulative lifetime levels of estrogen (a score of 3-5) had a significantly reduced PD risk [(OR = 0.57, 95% CI = 0.35, 0.91) relative to those with lower lifetime estrogen exposure or a composite estrogen summary score of 0-1].

These results provide some support for the hypothesis that lifelong high estrogen is protective in PD, suggesting that the level and persistence of exposure over the long term may be important in PD risk reduction.