Short-term effects of high-dose 17beta-estradiol in postmenopausal PD patients: a crossover study.
ABSTRACT 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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ABSTRACT: Recent results from laboratory investigations and clinical trials indicate important roles for estrogen receptor (ER) agonists in protecting the central nervous system (CNS) from noxious consequences of neuroinflammation and neurodegeneration. Neurodegenerative processes in several CNS disorders including spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD) are associated with activation of microglia and astrocytes, which drive the resident neuroinflammatory response. During neurodegenerative processes, activated microglia and astrocytes cause deleterious effects on surrounding neurons. The inhibitory activity of ER agonists on microglia activation might be a beneficial therapeutic option for delaying the onset or progression of neurodegenerative injuries and diseases. Recent studies suggest that ER agonists can provide neuroprotection by modulation of cell survival mechanisms, synaptic reorganization, regenerative responses to axonal injury, and neurogenesis process. The anti-inflammatory and neuroprotective actions of ER agonists are mediated mainly via two ERs known as ERα and ERβ. Although some studies have suggested that ER agonists may be deleterious to some neuronal populations, the potential clinical benefits of ER agonists for augmenting cognitive function may triumph over the associated side effects. Also, understanding the modulatory activities of ER agonists on inflammatory pathways will possibly lead to the development of selective anti-inflammatory molecules with neuroprotective roles in different CNS disorders such as SCI, MS, PD, and AD in humans. Future studies should be concentrated on finding the most plausible molecular pathways for enhancing protective functions of ER agonists in treating neuroinflammatory and neurodegenerative injuries and diseases in the CNS.Brain Research Bulletin 09/2014; 109. DOI:10.1016/j.brainresbull.2014.09.004 · 2.97 Impact Factor
06/2014; 1(2). DOI:10.1002/mdc3.12036
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ABSTRACT: Published data on the relationship of hormone replacement therapy (HRT) with Parkinson's disease (PD) were inconclusive. Thus, a systematic meta-analysis of observational studies was performed to clarify this topic. The databases of PubMed and EMBASE were searched for case-control or cohort studies published up till June 2, 2014. Meta-analysis of the relative risks (RRs) with 95% confidence intervals (CIs) was estimated using random-effects models. A final total of ten case-control and four cohort studies were included in our meta-analysis. The overall combined RR of PD for ever users versus never users of HRT was 1.00 (95% CI: 0.84-1.20). Limited to those subjects who only use estrogen, a similar trend was detected (RR: 0.95, 95% CI: 0.69-1.30). In the subgroup analysis by study design, no significant association was observed in case-control studies (RR: 0.79, 95% CI: 0.62-1.02), whereas a positive association was found in cohort studies (RR: 1.24, 95% CI: 1.10-1.40). In further analysis according to study quality, an inverse association was found in the low-quality group (RR: 0.58, 95% CI: 0.40-0.82), whereas a positive association was found in the high-quality group (RR: 1.16, 95% CI: 1.02-1.31). In summary, our results of meta-analysis do not support a protective role of HRT in female PD development.Neuropsychiatric Disease and Treatment 01/2015; 11:59-66. DOI:10.2147/NDT.S69918 · 2.00 Impact Factor