Short-term effects of high-dose 17 -estradiol in postmenopausal PD patients: A crossover study

Baylor University, Waco, Texas, United States
Neurology (Impact Factor: 8.29). 08/1999; 53(1):91-5. DOI: 10.1212/WNL.53.1.91
Source: PubMed


To examine the effect of 17beta-estradiol on the severity of the cardinal signs of PD in postmenopausal women.
Although the impact of estrogens on the manifestations of PD has not been subjected to rigorous study, their use is generally thought to be associated with a detrimental antidopaminergic effect.
A double-blind, placebo-controlled, two-arm crossover study of high-dose transdermal 17beta-estradiol was conducted in eight postmenopausal women with mild to moderate PD, all but one of whom exhibited levodopa-induced dyskinesias. Patients were randomized initially to either hormonal treatment or placebo for 2 weeks, followed by a 2-week washout period, and then another 2-week crossover treatment period. Active treatment employed four skin patches each releasing 0.1 mg of estradiol daily, replaced every 2 to 3 days.
After 10 days of treatment a significant reduction was observed in the antiparkinsonian threshold dose of IV levodopa. Mean duration and magnitude of the antiparkinsonian response to threshold or high doses of levodopa were unchanged, and dyskinesia scores were unaltered during 17beta-estradiol treatment compared with placebo. No worsening in "on" time or motor ratings with estrogen treatment was documented.
17beta-estradiol appears to display a slight prodopaminergic (or antiparkinsonian) effect without consistently altering dyskinesias. Standard postmenopausal replacement therapy with transdermal 17beta-estradiol is likely to be well tolerated by many female parkinsonian patients.

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    • "Parkinson's disease is caused by decreased dopamine transmission in the STR, and Parkinson's patients show hippocampal atrophy and decreased markers of neurogenesis in the dentate gyrus (for review see Regensburger et al., 2014).There is a higher incidence of Parkinson's in males (Shulman and Bhat, 2006), however, Parkinson's symptoms in females increase following menopause when endogenous estrogen production decreases (Ragonese et al., 2004). Moreover, women respond better to L-3,4-dihydroxyphenylalanine (L-DOPA), the first line treatment for Parkinson's disease, when it is administered with transdermal E2 (Blanchet et al., 1999). Schizophrenia is also hypothesized to result from dysregulated dopamine transmission, with increased dopamine activity in the NAc and STR, and decreased dopamine transmission in the PFC (Howes and Kapur, 2009). "
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    ABSTRACT: Over the past 30 years, research has demonstrated that estrogens are not only important for female reproduction, but play a role in a diverse array of cognitive functions. Originally, estrogens were thought to have only one receptor, localized exclusively to the cytoplasm and nucleus of cells. However, it is now known that there are at least three estrogen receptors (ERs): ERα, ERβ and G-protein coupled ER1 (GPER1). In addition to being localized to nuclei, ERα and ERβ are localized to the cell membrane, and GPER1 is also observed at the cell membrane. The mechanism through which ERs are associated with the membrane remains unclear, but palmitoylation of receptors and associations between ERs and caveolin are implicated in membrane association. ERα and ERβ are mostly observed in the nucleus using light microscopy unless they are particularly abundant. However, electron microscopy has revealed that ERs are also found at the membrane in complimentary distributions in multiple brain regions, many of which are innervated by dopamine inputs and were previously thought to contain few ERs. In particular, membrane-associated ERs are observed in the prefrontal cortex, dorsal striatum, nucleus accumbens, and hippocampus, all of which are involved in learning and memory. These findings provide a mechanism for the rapid effects of estrogens in these regions. The effects of estrogens on dopamine-dependent cognition likely result from binding at both nuclear and membrane-associated ERs, so elucidating the localization of membrane-associated ERs helps provide a more complete understanding of the cognitive effects of these hormones. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jun 2015 · Hormones and Behavior
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    • "International Journal of Alzheimer's Disease Table 4: RCTs of ERT and Parkinson's disease. Study (reference) Hormone treatment used Sample Size Outcome measure Overall findings Blanchet [34] "
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    ABSTRACT: Over the past two decades, there has been a significant amount of research investigating the risks and benefits of hormone replacement therapy (HRT) with regards to neurodegenerative disease. Here, we review basic science studies, randomized clinical trials, and epidemiological studies, and discuss the putative neuroprotective effects of HRT in the context of Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and HIV-associated neurocognitive disorder. Findings to date suggest a reduced risk of Alzheimer's disease and improved cognitive functioning of postmenopausal women who use 17β-estradiol. With regards to Parkinson's disease, there is consistent evidence from basic science studies for a neuroprotective effect of 17β-estradiol; however, results of clinical and epidemiological studies are inconclusive at this time, and there is a paucity of research examining the association between HRT and Parkinson's-related neurocognitive impairment. Even less understood are the effects of HRT on risk for frontotemporal dementia and HIV-associated neurocognitive disorder. Limits to the existing research are discussed, along with proposed future directions for the investigation of HRT and neurodegenerative diseases.
    Full-text · Article · Apr 2012 · International Journal of Alzheimer's Disease
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    • "Postmenopausal women with early PD using estrogen therapy prior to initiation of levodopa have lower symptom severity scores (Saunders-Pullman et al., 1999) but estrogen therapy had no effect at later stages of the disease (Strijks et al., 1999). Results from double-blind studies reported a reduction of the dose of levodopa required to improve motor function in women receiving 17β-estradiol (Blanchet et al., 1999) and an improvement of motor disability in PD women with motor fluctuations when treated with estrogens (Tsang et al., 2000) whereas no effect of estrogen on motor function was also observed (Strijks et al., 1999). While in some cases conflicting information is reported from the above human studies, a longer fertile lifespan seems to be consistently associated with a decreased risk of PD, suggesting that longer exposure to endogenous ovarian steroids exerts a beneficial effect against PD. "
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    Full-text · Article · Sep 2011 · Frontiers in Endocrinology
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