Estrogen replacement therapy and cognitive functions in healthy postmenopausal women: a randomized trial Clarice Gorenstein & Joel Rennó Jr & Antônio Hélio Guerra Vieira Filho & Arlete Gianfaldoni & Marcelo Alfonso Gonçalves & Hans Wolfgang Halbe & César Eduardo Fernandes & Frederico Navas Demétrio
Received: 13 September 2010 / Accepted: 22 June 2011 # Springer-V erlag 2011
Abstract This study aimed to evaluate the effect of estrogen replacement therapy on verbal cognitive performance of middle-aged postmenopausal women. Middleaged (40 to 59 years) hysterectomized, oligosymptomatic women receiving 0.625 mg/day of conjugated equine estrogens (N=27) or placebo (N=32) in a double-blind parallel group design were compared according to their performance on a verbal memory battery before and after six 28-day cycles of treatment. Both groups had similar age
and educational level. The estrogen group performed better on digit span-forward and on the recall of the easy stimuli on the verbal-paired associates test regardless of age, education, physical symptoms, number of years of menopause, or blood estradiol levels. However, the small magnitude of difference in the effect on attentional span suggests that the estrogen-related improvement is unlikely to be of clinical relevance. Estrogen replacement therapy did not improve verbal memory in middle-aged, hysterectomized, postmenopausal, asymptomatic women. Keywords Menopause . Estradiol . Estrogen replacement therapy . Cognition
C. Gorenstein (*) Instituto de Psiquiatria, LIM-23 Rua Ovidio Pires de Campos, 785 - térreo, CEP 05403-010 São Paulo, Brazil e-mail: email@example.com C. Gorenstein Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil C. Gorenstein LIM-23, Laboratory of Psychopharmacology of the Clinical Hospital, Medical School of the University of São Paulo (HCFMUSP), São Paulo, Brazil J. Rennó Jr : A. H. G. Vieira Filho : F. N. Demétrio Institute of Psychiatry of HCFMUSP , São Paulo, Brazil A. Gianfaldoni : M. A. Gonçalves : C. E. Fernandes Department of Gynecology and Obstetrics of FMUSP , São Paulo, Brazil H. W. Halbe Department of Obstetrics and Gynecology, Medical School of Marília, São Paulo, Brazil
Introduction A large body of evidence supports a role of estrogen in higher cognitive functions (e.g., Woolley et al. 1997; Behl 2002; Kipp et al. 2006; Hojo et al. 2008). To better understand the neurobiological effects of estrogen in cognition, Maki and Dumas (2009) reviewed data from functional neuroimaging and pharmacologic challenge studies assessing estrogen–neurotransmitter interactions. These authors concluded that estrogen interacts with cholinergic and serotonergic systems to alter the function of hippocampal and frontal cortical brain areas thereby enhancing memory, particularly at the retrieval stage of memory processing. Considering these data, it is reasonable to predict that estrogen replacement therapy (ET) would attenuate the deficits of cognitive function associated with estrogen decrease, resulting in beneficial effects to menopausal women. Indeed, a number of studies aimed to evaluate this hypothesis but they lead to inconsistent results. Many of
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them show that postmenopausal women on ET tend to perform better on tests of explicit verbal memory and working memory compared to non-users of estrogen (Sherwin 2003). Among others, age is one of the confounding variables to be considered in randomized controlled studies with ET. In postmenopausal women up to 60 years old, ET was either associated with better performance on cognitive tests (Kimura 1995; Aveleyra et al. 2005), or no effect (Kurt et al. 2006; LeBlanc et al. 2007). The Women’s Health Initiative Memory Study (Shumaker et al. 2004) is the largest study conducted in postmenopausal women to assess the effects of hormone therapy (HT) on...