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22 November 2008
22 November 2008
| Chronic Estradiol Exposure And Impaired Working Memory |
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| Medicine - Hormones & Meds | |||
| Written by TS-Si News Service | |||
| Thursday, 07 August 2008 16:30 | |||
Urbana, IL, USA. The main estrogen in the female body is estradiol. Doctors often prescribe Hormone Replacement (HT) regimens that only mimic the effects of estradiol, such as conjugated estrogens and other substances. Other women rely on phytoestrogens from plants that only approximate the effects of estradiol.
Both approaches have effects that vary from dangerous to ineffective and lack the direct — and safer — dosages available from actual estradiol preparations. Even though the relative safety of estradiol has been established, are there other effects that should be considered?
Effects of Chronic Estradiol Treatment on Delayed Spatial Alternation and Differential Reinforcement of Low Rates of Responding. Victor C. Wang, Helen J. K. Sable, Young H. Ju, Clinton D. Allred, William G. Helferich, Donna L. Korol, and Susan L. Schantz. Behavioral Neuroscience 122(4) 794–804. doi: 10.1037 / a0012513.
Researchers at the University of Illinois report that chronic exposure to estradiol can diminish some cognitive functions. Rats exposed to a steady dose of estradiol were impaired on tasks involving working memory and response inhibition, the researchers found. Their report appears in the journal Behavioral Neuroscience.
The researchers made the discovery when studying the effects of estradiol on activities mediated by the prefrontal cortex, a brain region that is vital to working memory and to the ability to plan, respond to changing conditions and moderate or control one's behavior.
 (L) Susan L. Schantz, a University of Illinois professor of veterinary biosciences and principal investigator.; (R) Neuroscience graduate student Victor C. Wang, the lead author. Photo by L. Brian Stauffer.
Working memory is the ability to briefly remember information needed for a particular task, says Susan Schantz. An example in humans is a phone number that is forgotten soon after the number is dialed. "With working memory you're just keeping it active until you use it."
The investigators had not expected to see such pronounced results. In fact, the study originally had been designed to give them baseline information for a separate inquiry into the effects of soybean estrogens on cognitive function.
They planned to compare the effects of chronic estradiol exposure to the effects of chronic exposure to genistein, a phytoestrogen found in soybeans. Genistein is believed to have similar, but not exactly equivalent, effects in the body as natural or synthetic estrogens. However, no study has definitively proven this to be so.
In the new study, rats were trained to press one of two levers to obtain a food reward.
A second set of tests measured the rats' ability to wait before responding to a stimulus.
"That's the test where we really saw the most striking effects with estradiol," Schantz said. The estradiol-treated rats "were not as good at waiting," she said.
"Rats treated with estradiol are definitely a lot more active and make a lot more lever presses," said neuroscience graduate student Victor C. Wang, the study's lead author. "That's not conducive toward being rewarded."
Schantz and her colleagues had focused on the prefrontal cortex because it is rich in estrogen receptor beta (ER-beta), a protein that spurs gene expression and other activities in the cell when it binds to estradiol. Genistein also activates ER-beta.
Some women take genistein supplements or eat soy-based foods to reduce hot flashes or other symptoms of menopause, Schantz said. "Women take them thinking they'll be a safe alternative to hormone-replacement therapy and they might help hot flashes," she said. Those who have heard that hormone replacement can improve cardiac or brain function also hope that eating soy or taking genistein supplements will have the same effects, she said.
The effects of hormone replacement therapy (HRT) are more complex – and problematic – than once thought. Large-scale studies of the effects of hormones generally use conjugated estrogen preparations and synthetic progestins (e.g., medoxyprogesterone). These are problematic substances when compared to the relative safety of estradiol and nd a true progestin (e.g., prometrium.
The recent results of hormone studies using conjugated estrogen preparations and synthetic progestins have not been encouraging. A recent large-scale study of HRT in post-menopausal women was stopped because of an increased risk of stroke and blood clots in women taking estrogen alone, and a higher than average incidence of breast cancer, cardiovascular disease, blood clots and stroke in women taking estrogen and progesterone.
Studies of estrogen's effects on cognition have also had mixed results. In earlier studies, for example, psychology professor Donna L. Korol, a collaborator on the current project, found that estradiol enhances some abilities, such as place or spatial learning, while hindering others, such as learning that relies on stimulus-response associations, considered by some to be akin to "habit" and not fluid thought.
Performance in these tasks involves brain structures outside the prefrontal cortex.
The research indicates that multiple factors influence the effects of estradiol on the brain, Schantz said. The timing of the exposure, the types of brain functions or structures studied and the age of the test subjects can all generate different results, she said.
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The TS-Si News Service is a collaboration of TS-Si staff, contributors, and corresponding institutions. Contents do not necessarily convey official positions of TS-Si, its partners, or affiliates