Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental and Genetic PSP study

Park, Hee Kyung; Ilango, Sindana D.; Charriez, C. M.; Checkoway, Harvey; Riley, David E.; Standaert, David G.; Bordelon, Yvette; Shprecher, David; Reich, Stephen G.; Hall, Deborah A.; Kluger, Benzi M.; Marras, Connie; Jankovic, Joseph; Dubinsky, Richard; Litvan, Irene; Study, Engene-Psp

doi:10.1002/mds.27336

Cited by 16 publications

(7 citation statements)

References 44 publications

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“…CES totals ranged from 0 to 5. Hysterectomy is most commonly indicated for fibroids, which are benign tumors that are dependent on estrogen presence (14,15). Thus, hysterectomy without oophorectomy serves as a surrogate marker of estrogen exposure and was included in the CES as in previous similar composite scores (13,16).…”

Section: Methodsmentioning

confidence: 99%

Association of Sjögren's Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case–Control Study

McCoy

Sampene

Baer

2020

Arthritis Care & Research

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Objective To test whether cumulative estrogen exposure, as determined by age at menarche, age at menopause, female hormone use, hysterectomy, and parity, have an effect on the development of primary Sjögren's syndrome (SS). Methods We performed a case–control study of 2,680 women from the Sjögren's International Collaborative Clinical Alliance registry, including 1,320 registrants with primary SS and 1,360 with sicca symptoms but no key features of primary SS (sicca controls). The composite estrogen score (CES) was calculated by point assignment for early menarche (age ≤10 years), high parity (>3 pregnancies), hysterectomy, female hormone use, and late menopause (age ≥53 years). Cumulative menstrual cycling (CMC) was calculated as years menstruating minus time pregnant. Results Using a regression model that adjusted for age, recruitment site, ethnicity, education, employment status, and smoking, we observed a progressive inverse trend between primary SS and CES. The odds ratio (OR) and 95% confidence interval (95% CI) were as follows for the sicca control group: CES 1, OR 0.81 (95% CI 0.67–0.99); CES 2, OR 0.74 (95% CI 0.57–0.97); CES 3, OR 0.50 (95% CI 0.30–0.86). This trend was corroborated by analysis of CMC. At the highest level of CMC within the postmenopausal group there was a 24% reduction in cumulative sex hormone exposure among primary SS participants relative to controls. Conclusion Women with primary SS have lower estrogen exposure and CMC compared to sicca controls. Increasing estrogen exposure was negatively associated with development of primary SS. Further longitudinal studies of sex hormone exposure in primary SS are needed to confirm these findings.

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Section: Methodsmentioning

confidence: 99%

Association of Sjögren's Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case–Control Study

McCoy

Sampene

Baer

2020

Arthritis Care & Research

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“…Age at menopause was estimated using the age at the last menstrual cycle or at the time of bilateral oophorectomy. Lifetime exposure to estrogen (estrogen exposure length) was the sum of difference between age at menopause and menarche (reproductive years) and years of estrogen replacement therapy (ERT) use 12 . The estrogen deprivation length was the difference between age at PD onset and estrogen exposure length.…”

Section: Methodsmentioning

confidence: 99%

Beneficial effect of estrogen on nigrostriatal dopaminergic neurons in drug-naïve postmenopausal Parkinson’s disease

Lee

Cha

Chung

et al. 2019

Sci Rep

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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.

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“…Lower education levels (high school completion or lower versus college completion or higher) are associated with incident PSP, and studies have indicated associations with duration of exposure to well water and industrial waste. In a study of 150 women with clinically diagnosed PSP and 150 age-matched control women, any exposure to estrogen replacement therapy was associated with a halved risk of PSP (odds ratio, 0.52; 95% CI, 0.30-0.92; P =.03) 6 …”

Section: Progressive Supranuclear Palsymentioning

confidence: 99%

Progressive Supranuclear Palsy and Corticobasal Syndrome

Pantelyat¹

2022

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEW:The differential diagnosis of parkinsonism (tremor, rigidity, bradykinesia, and gait difficulty/postural instability) is broad and includes two neurodegenerative conditions that exist on a clinicopathologic spectrum: progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Early in their clinical course, PSP and CBS may be difficult to distinguish from Parkinson disease and several other illnesses, but it is crucial to do so because of implications for management and prognosis.RECENT FINDINGS: Early accurate diagnosis of PSP and CBS remains a challenge because of heterogeneity in presenting symptoms and high frequency of coexisting pathologies (especially Alzheimer disease and vascular disease). It is increasingly recognized that patients with PSP, CBS, and other parkinsonian disorders require multidisciplinary care for optimal outcomes. With the recent proliferation of biomarker studies and therapeutic trials for tauopathies, there is growing hope that better treatments for PSP and CBS are on the horizon. SUMMARY: Although PSP and CBS currently lack disease-modifying therapies, it is important to diagnose them as early as possible so that the patient can benefit from the many available symptomatic therapies, support groups, and a growing number of clinical trials.

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Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental and Genetic PSP study

Abstract: This case-control study suggests a protective role of lifetime estrogen exposure in PSP. Future studies will be needed to confirm this association. © 2018 International Parkinson and Movement Disorder Society.

Cited by 16 publications

References 44 publications

Association of Sjögren's Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case–Control Study

Association of Sjögren's Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case–Control Study

Beneficial effect of estrogen on nigrostriatal dopaminergic neurons in drug-naïve postmenopausal Parkinson’s disease

Progressive Supranuclear Palsy and Corticobasal Syndrome

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