Abstract
This study aimed to investigate the potential beneficial effects of estrogen on nigrostriatal dopaminergic neuron degeneration in postmenopausal drug-naïve Parkinson’s disease (PD). Based on the ratio of lifetime estrogen exposure length to the total length of the estrogen exposure and deprivation period, postmenopausal women with drug-naïve PD were divided into low (n = 31) and high (n = 31) estrogen exposure ratio groups. We performed a comparative analysis of the striatal dopamine transporter (DAT) availability between the two groups. Additionally, we evaluated the longitudinal change in the levodopa equivalent dose per month using a linear mixed model. The motor symptoms were more severe in the low estrogen exposure ratio group than in the high estrogen exposure ratio group (P = 0.016). PD patients in the two groups had significantly lower DAT availability on all striatal sub-regions except for ventral striatum than did age- and sex-matched normal controls. When comparing the two groups, PD patients in the low estrogen exposure ratio group exhibited significantly lower DAT availability in the posterior putamen (P = 0.024) and in the ventral putamen (P = 0.036) than those in the high estrogen exposure ratio group. The estimated monthly levodopa equivalent dose changes were 10.9 in the low estrogen exposure ratio group and 7.1 in the high estrogen exposure ratio group with a significant interaction between the two groups (P = 0.001). These in vivo data provide indirect evidence showing that estrogen may elicit a beneficial effect on nigrostriatal dopamine neurons in PD.
Highlights
Epidemiologic studies have revealed that the prevalence of Parkinson’s disease (PD) is 1.5–2-fold lower in women than in men[1,2], suggesting a possible protective influence of estrogen in predilection to the disease
PD patients in the low exposure and deprivation period (Eratio) group were older at PD onset (67.6 ± 1.3 vs 55.9 ± 1.3, P < 0.001) than those in the high Eratio group
The estrogen exposure length was significantly shorter in the low Eratio group than in the high Eratio group (P < 0.001), and the total length of estrogen exposure and deprivation period was significantly longer in the low Eratio group than in the high Eratio group (P < 0.001)
Summary
Epidemiologic studies have revealed that the prevalence of Parkinson’s disease (PD) is 1.5–2-fold lower in women than in men[1,2], suggesting a possible protective influence of estrogen in predilection to the disease. Observational studies have indicated that increased length of estrogen exposure period was correlated with less severe PD symptoms and that the risk of developing PD was increased in women with experience of surgical menopause[5,6] These data suggest that estrogen may have a protective effect on dopaminergic neurons in PD. One animal study reported that long-term estrogen deprivation by prolonged ovariectomy in primates might be an important determinant in maintaining nigrostriatal dopamine neurons[9]. This finding suggests that the total length of lifetime estrogen exposure, and the total period of estrogen deprivation might be crucial factors to modulate the loss of dopaminergic neurons. We evaluated the influence of Eratio on the longitudinal requirement of dopaminergic medications in these patients
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