Effects of Combination Estrogen Plus Progestin Hormone Treatment on Cognition and Affect

University of Nevada, Reno, Reno, Nevada, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 05/2006; 91(5):1802-10. DOI: 10.1210/jc.2005-2097
Source: PubMed


Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory.
The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women.
This study was a randomized, double-blind, placebo-controlled clinical trial.
Participants were women from 14 of 40 clinical centers of the Women's Health Initiative (WHI).
Postmenopausal women (1416) aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr, were studied.
Intervention was conjugated equine estrogen (CEE; 0.625 mg) with 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet (CEE + MPA) or placebo.
Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.
CEE + MPA had a negative impact on verbal memory (P <or= 0.01) and a trend to a positive impact on figural memory (P = 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long-term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms.
The effect of CEE + MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research.

Download full-text


Available from: Pauline M Maki, Jan 29, 2015
  • Source
    • "We examined data from the Women's Health Initiative Study of Cognitive Aging (WHISCA) [16, 25, 26] to determine if IAV Cognitive Domains and IAV Time predict risk of MCI and incident dementia, addressing two main questions. First, we examined whether IAV Cognitive Domains predicts risk of MCI and dementia above and beyond mean overall and domain-specific interindividual differences in cognition. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Intraindividual variability among cognitive domains may predict dementia independently of interindividual differences in cognition. A multidomain cognitive battery was administered to 2305 older adult women (mean age 74 years) enrolled in an ancillary study of the Women's Health Initiative. Women were evaluated annually for probable dementia and mild cognitive impairment (MCI) for an average of 5.3 years using a standardized protocol. Proportional hazards regression showed that lower baseline domain-specific cognitive scores significantly predicted MCI (N = 74), probable dementia (N = 45), and MCI or probable dementia combined (N = 101) and that verbal and figural memory predicted each outcome independently of all other cognitive domains. The baseline intraindividual standard deviation across test scores (IAV Cognitive Domains) significantly predicted probable dementia and this effect was attenuated by interindividual differences in verbal episodic memory. Slope increases in IAV Cognitive Domains across measurement occasions (IAV Time) explained additional risk for MCI and MCI or probable dementia, beyond that accounted for by interindividual differences in multiple cognitive measures, but risk for probable dementia was attenuated by mean decreases in verbal episodic memory slope. These findings demonstrate that within-person variability across cognitive domains both at baseline and longitudinally independently accounts for risk of cognitive impairment and dementia in support of the predictive utility of within-person variability.
    Current Gerontology and Geriatrics Research 12/2013; 2013:495793. DOI:10.1155/2013/495793
  • Source
    • "Women's Health Initiative Memory Study randomized controlled trial [22] as well as in a subgroup of women of the 3C study [23]. Whether women with treatment-resistant high LDL-cholesterol and not treated with hormonal treatment may be at increased risk of decline in visual memory remains to be further examined. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this prospective cohort study was to evaluate the effects of lipid lowering agent (LLA) intake on cognitive function in 6,830 community-dwelling elderly persons. Cognitive performance (global cognitive functioning, visual memory, verbal fluency, psychomotor speed, and executive function), clinical diagnosis of dementia, and fibrate and statin use, were evaluated at baseline, and 2, 4, and 7 year follow-up. Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics, mental and physical health including vascular risk factors, and genetic vulnerability (apolipoprotein E and cholesteryl ester transfer protein). For women but not men, fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only (HR = 1.29, 95% CI = 1.09-1.54, p = 0.004), and did not increase risk for incident dementia. This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate (HR = 1.39, 95% CI = 1.08-1.79, p = 0.01) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment. For both genders, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence. This prospective study, adjusting for multiple confounders, found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia, but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory.
    Journal of Alzheimer's disease: JAD 03/2012; 30(3):629-37. DOI:10.3233/JAD-2012-120064 · 4.15 Impact Factor
  • Source
    • "In addition, genetic studies have also shown an association between variants of the gene CYP19a (aromatase ; Iivonen et al., 2004), altered levels of ERα mRNA and protein (Ishunina and Swaab, 2008), and variants in the ERβ gene (Pirskanen et al., 2005) with risk for Alzheimer's disease. Several clinical studies have suggested a beneficial role of estradiol plus progestin in the treatment of Alzheimer's disease (Resnick et al., 2006); however, this beneficial role has also been challenged (Rossouw et al., 2002; Rapp et al., 2003; Espeland et al., 2004; Shumaker et al., 2004). Preclinical studies have also supported a role of estradiol in a neuroprotective role. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Estrogens have multiple actions in the brain including modulating synaptic plasticity, connectivity, and cognitive behaviors. While the classical view of estrogens are as endocrine signals, whose effects manifest via the regulation of gene transcription, mounting evidence has been presented demonstrating that estrogens have rapid effects within specific areas of the brain. The emergence that 17 β-estradiol can be produced locally in the brain which can elicit rapid (within minutes) cellular responses has led to its classification as a neurosteroid. Moreover, recent studies have also begun to detail the molecular and cellular underpinnings of how 17 β-estradiol can rapidly modulate spiny synapses (dendritic spines). Remodeling of dendritic spines is a key step in the rewiring of neuronal circuitry thought to underlie the processing and storage of information in the forebrain. Conversely, abnormal remodeling of dendritic spines is thought to contribute to a number of psychiatric and neurodevelopmental disorders. Here we review recent molecular and cellular work that offers a potential mechanism of how 17 β-estradiol may modulate synapse structure and function of cortical neurons. This mechanism allows cortical neurons to respond to activity-dependent stimuli with greater efficacy. In turn this form of plasticity may provide an insight into how 17 β-estradiol can modulate the rewiring of neuronal circuits, underlying its ability to influencing cortically based behaviors. We will then go on to discuss the potential role of 17 β-estradiol modulation of neural circuits and its potential relevance for the treatment of psychiatric and neurodevelopmental disorders.
    Frontiers in Endocrinology 11/2011; 2:77. DOI:10.3389/fendo.2011.00077
Show more