Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: evidence for the critical period hypothesis.

Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect St., Burlington, VT 05401, USA.
Hormones and Behavior (Impact Factor: 4.51). 02/2008; 53(1):159-69. DOI: 10.1016/j.yhbeh.2007.09.011
Source: PubMed

ABSTRACT Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50-62) and older (ages 70-81) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed. Subjects were administered either the antimuscarinic drug scopolamine (SCOP), the antinicotinic drug mecamylamine (MECA), or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory (the Buschke Selective Reminding Task) for the younger group only, while estradiol treatment impaired performance of the older group. The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects, supporting the concept of a critical period for postmenopausal estrogen use.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women's brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the left inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in several cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain.
    Frontiers in Neuroscience 12/2014; 8:388. DOI:10.3389/fnins.2014.00388
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the current study, we explored the potential effects of hormone therapy (HT) on language functioning in healthy, postmenopausal women and compared them with men of similar ages. Language functioning on tasks of verbal fluency and object naming was examined in 100 participants (mean age: 61.9 years; 33 HT users, 15 HT non-users and 52 men) at baseline and follow-up (mean follow-up time period: 2.6 years). At baseline, men had higher composite language scores than HT users. However, HT users demonstrated more improvement over time compared with men, whereas HT non-users performed similarly to men, with no improvement over time. Longer duration of HT use was not associated with improved performance on language tests. These results suggest an association between HT use and better language ability in postmenopausal women.
    Aging Health 12/2012; 8(6):625-632. DOI:10.2217/ahe.12.66
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extensive evidence suggests that decline in ovarian function with menopause is associated with neuronal dysfunction. Major cause of this is rise in oxidative stress and inflammatory cytokines because of estrogen deficiency. 17β-Estradiol (E2, hormone with potent antioxidant and anti-inflammatory activity) has profound protective actions on multiple organ systems, but feminizing side effects of β-estradiol limits its clinical efficacy. 17α-Estradiol (E2α), a non feminizing congener, gives a ray of hope to the scientific community as an alternative strategy to treat menopause associated neuronal pathologies. We assessed the protective actions of 17α-estradiol (5, 10μg/kg) against cognitive deficits, depression and motor coordination after 4weeks of ovariectomy in rats and compared its efficacy with E2 at same doses. After the behavioral assay animals were sacrificed and their brains were harvested for biochemical studies. Uterine weights were also assessed. E2 and E2α (5, 10μg/kg) were equally protective against attenuating cognitive deficits, depressive symptoms and motor incoordination in OVX rats. Both demonstrated significant antioxidant activity and E2, but not E2α, increased serum estradiol levels and proliferated uterine weights, markers of feminizing action. It can thus be concluded that E2α offers safe alternative to E2 in protecting against menopausal neuropathologies. Copyright © 2015. Published by Elsevier Inc.
    Steroids 01/2015; 96. DOI:10.1016/j.steroids.2015.01.004 · 2.72 Impact Factor

Full-text (2 Sources)

Available from
Jun 1, 2014