Gender differences and the effects of synthetic exogenous and non-synthetic estrogens in focal cerebral ischemia

Vergouwen, Mervyn D.I.; Anderson, Robert E.; Meyer, Fredric B.

doi:10.1016/s0006-8993(00)02713-x

Cited by 33 publications

(22 citation statements)

References 60 publications

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“…Four articles reported no difference between placebo and estrogen treatments (Farr et al, 2006;Goodrow et al, 2005;Santizo et al, 2002;Vergouwen et al, 2000).…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 98%

Dose-Related Neuroprotective versus Neurodamaging Effects of Estrogens in Rat Cerebral Ischemia: A Systematic Analysis

Ström

Theodorsson

2009

J Cereb Blood Flow Metab

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Numerous studies of the effects of estrogens for stroke prevention have yielded conflicting results in human and animal studies alike. We present a systematical analysis of study design and methodological differences between 66 studies where estrogens' impact on ischemic brain damage in rat models has been investigated, providing evidence that the differences in results may be explained by high estrogen doses produced by slow-release pellets. These pellets have been used in all studies showing increased neurologic damage because of estrogens. Our data indicate that the increased neurologic damage is related to the pellets' plasma concentration profile with an early, prolonged, supraphysiological peak. Neither the method of inducing the ischemic brain lesions, the choice of variables for measuring outcome, the measured plasma concentrations of estrogens at the time of ischemia nor rat population attributes (sex, strain, age, and diseases) are factors contributing to the discrepancies in results. This suggests that the effects of estrogens for stroke prevention are concentration related with a complex dose-response curve, and underscores the importance of carefully validating the experimental methods used. Future studies of hormonereplacement therapy in women may have to take dosage and administration regimens into account.

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“…Four articles reported no difference between placebo and estrogen treatments (Farr et al, 2006;Goodrow et al, 2005;Santizo et al, 2002;Vergouwen et al, 2000).…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 98%

Dose-Related Neuroprotective versus Neurodamaging Effects of Estrogens in Rat Cerebral Ischemia: A Systematic Analysis

Ström

Theodorsson

2009

J Cereb Blood Flow Metab

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“…39,40 E2 may also be less beneficial with increased severity of injury, e.g., prolonged or permanent vessel occlusion as opposed to transient occlusion. 41,42 In some models of comorbidity, such as diabetes, E2 increases infarct size 43 and postischemic inflammation. 44,45 Some of these effects may be model-related.…”

Section: Estrogen and Ibi: What We Know From The Benchmentioning

confidence: 99%

Gender and the injured brain

Herson

Hurn

2010

Progress in Brain Research

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“…However, experimental studies have established that young adult female rodents sustain smaller injury than males after global/forebrain (Hall et al 1991;Hurn and Macrae 2000;Payan and Conard 1977) or focal ischemia (Alkayed et al 1998;Hurn and Macrae 2000;Hurn et al 2002;Li et al 1996;Wise et al 2001;Zhang et al 1998). One study in a rat transient focal ischemia model showed no gender differences (Vergouwen et al 2000). This overall neuroprotective effect of female gender on ischemic injury is still evident even in the presence of specific stroke risk factors such as diabetes (Toung et al 2000;Vannucci et al 2001) and hypertension (Alkayed et al 1998;Cai et al 1998;Carswell et al 1999;Okamoto et al 1974;Sadoshima et al 1988).…”

Section: Animal Studiesmentioning

confidence: 99%

Stroke in the Female: Role of Biological Sex and Estrogen

Murphy¹,

McCullough²,

Smith³

2004

ILAR Journal

108

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Women are protected from stroke relative to men until the years of menopause. Because stroke is the leading cause of serious, long-term disability in the United States, modeling sex-specific mechanisms and outcomes in animals is vital to research. Important research questions are focused on the effects of hormone replacement therapy, age, reproductive status, and identification of sex-specific risk factors. Available research relevant to stroke in the female has almost exclusively utilized rodent models. Gender-linked stroke outcomes are more detectable in experimental studies than in clinical trials and observational studies. Various estrogens have been extensively studied as neuroprotective agents in women, animals, and a variety of in vitro models of neural injury and degeneration. Most data in animal and cell models are based on 17 beta estradiol and suggest that this steroid is neuroprotective in injury from ischemia/reperfusion. However, current evidence for the clinical benefits of hormone replacement therapy is unclear. Future research in this area will need to expand into stroke models utilizing higher order, gyrencephalic animals such as nonhuman primates if we are to improve extrapolation to the human scenario and to direct and enhance the design of ongoing and future clinical studies and trials.

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Gender differences and the effects of synthetic exogenous and non-synthetic estrogens in focal cerebral ischemia

Cited by 33 publications

References 60 publications

Dose-Related Neuroprotective versus Neurodamaging Effects of Estrogens in Rat Cerebral Ischemia: A Systematic Analysis

Dose-Related Neuroprotective versus Neurodamaging Effects of Estrogens in Rat Cerebral Ischemia: A Systematic Analysis

Gender and the injured brain

Stroke in the Female: Role of Biological Sex and Estrogen

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