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: 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.04/2012; 2012:258454. DOI:10.1155/2012/258454
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ABSTRACT: The existence of a sex difference in Parkinson's disease (PD) is observed as related to several variables, including susceptibility of the disease, age at onset, and symptoms. These differences between men and women represent a significant characteristic of PD, which suggest that estrogens may exert beneficial effects against the development and the progression of the disease. This paper reviews the neuroprotective and neuromodulator effects of 17β-estradiol and progesterone as compared to androgens in the nigrostriatal dopaminergic (NSDA) system of both female and male rodents. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD and methamphetamine toxicity faithfully reproduce the sex differences of PD in that endogenous estrogen levels appear to influence the vulnerability to toxins targeting the NSDA system. Exogenous 17β-estradiol and/or progesterone treatments show neuroprotective properties against NSDA toxins while androgens fail to induce any beneficial effect. Sex steroid treatments show male and female differences in their neuroprotective action against methamphetamine toxicity. NSDA structure and function, as well as the distribution of estrogen receptors, show sex differences and may influence the susceptibility to the toxins and the response to sex steroids. Genomic and non-genomic actions of 17β-estradiol converge to promote survival factors and the presence of both estrogen receptors α and β are critical to 17β-estradiol neuroprotective action against MPTP toxicity.Frontiers in Endocrinology 09/2011; 2:35. DOI:10.3389/fendo.2011.00035
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ABSTRACT: Depression is common in Parkinson's disease and an imbalance in serotonin neurotransmission could be implicated. Estradiol is reported to modulate brain serotonin systems of rodents and monkeys, but this has not been explored in primate models of Parkinson's disease. Thus, the present study investigated the effect of estradiol on 5-HT(1A) and 5-HT(2A) serotonin receptors in the cortex, striatum and raphe nucleus of long-term ovariectomized hemiparkinsonian monkeys. Seven monkeys were ovariectomized and received a month later a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Four years after lesion and ovariectomy, three received a month of treatment with 17β-estradiol and four the vehicle. Autoradiography of [(3)H]8-OH-DPAT specific binding to 5-HT(1A) receptors showed a decrease in the frontal cortex of monkeys treated with 17β-estradiol in both hemispheres of the brain. [(3)H]ketanserin specific binding to 5-HT(2A) receptors was increased in the frontal cortex and the striatum of monkeys treated with 17β-estradiol in both the lesioned and intact sides of the brain. Autoradiography of [(35)S]GTPγS specific binding stimulated with R-(+)-8-OH-DPAT showed a decrease in the percentage of stimulation in the frontal cortex of monkeys treated with 17β-estradiol in both hemispheres of the brain and in the dorsal raphe nucleus. Treatment with 17β-estradiol was initiated a long time after ovariectomy in monkeys to model post menopausal hormonal conditions and showed that serotonin receptors were still responsive in the brain regions investigated. These results support a role for 17β-estradiol on serotonin activity in Parkinson's disease and could be useful for treatment of depression associated with this disease.Neuropharmacology 03/2011; 60(4):642-52. DOI:10.1016/j.neuropharm.2010.11.024 · 4.82 Impact Factor