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Objectives To summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women. Background Complaints of impaired cognition and mood are common in the peri-menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon. Design A literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included. Patients Perimenopausal and menopausal women. Results Due to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a ‘critical window’ for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri-menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear. Conclusions Further study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence-based conclusions can be drawn.

Adjuvant treatment of cancer by chemotherapy is associated with cognitive impairment in some cancer survivors. Breast cancer patients are frequently also receiving endocrine therapy with selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) to suppress the growth of estradiol sensitive breast tumors. Estrogens are well-known, however, to target brain areas involved in the regulation of cognitive behavior. In this review clinical and basic preclinical research is reviewed on the actions of estradiol, SERMs and AIs on brain and cognitive functioning to see if endocrine therapy potentially induces cognitive impairment and in that respect may contribute to the detrimental effects of chemotherapy on cognitive performance in breast cancer patients. Although many clinical studies may be underpowered to detect changes in cognitive function, current basic and clinical reports suggest that there is little evidence that AIs may have a lasting detrimental effect on cognitive performance in breast cancer patients. The clinical data on SERMs are not conclusive, but some studies do suggest that tamoxifen administration may form a risk for cognitive functioning particularly in older women. An explanation may come from basic preclinical research which indicates that tamoxifen often acts agonistic in the absence of estradiol but antagonistic in the presence of endogenous estradiol. It could be hypothesized that the negative effects of tamoxifen in older women is related to the so-called window of opportunity for estrogen. Administration of SERMs beyond this so-called window of opportunity may not be effective or might even have detrimental effects similar to estradiol. (C) 2013 Elsevier Inc. All rights reserved.

Adjuvant treatment of cancer by chemotherapy is associated with cognitive impairment in some cancer survivors. Breast cancer patients are frequently also receiving endocrine therapy with selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) to suppress the growth of estradiol sensitive breast tumors. Estrogens are well-known, however, to target brain areas involved in the regulation of cognitive behavior. In this review clinical and basic preclinical research is reviewed on the actions of estradiol, SERMs and AIs on brain and cognitive functioning to see if endocrine therapy potentially induces cognitive impairment and in that respect may contribute to the detrimental effects of chemotherapy on cognitive performance in breast cancer patients. Although many clinical studies may be underpowered to detect changes in cognitive function, current basic and clinical reports suggest that there is little evidence that AIs may have a lasting detrimental effect on cognitive performance in breast cancer patients. The clinical data on SERMs are not conclusive, but some studies do suggest that tamoxifen administration may form a risk for cognitive functioning particularly in older women. An explanation may come from basic preclinical research which indicates that tamoxifen often acts agonistic in the absence of estradiol but antagonistic in the presence of endogenous estradiol. It could be hypothesized that the negative effects of tamoxifen in older women is related to the so-called window of opportunity for estrogen. Administration of SERMs beyond this so-called window of opportunity may not be effective or might even have detrimental effects similar to estradiol. (C) 2013 Elsevier Inc. All rights reserved.

Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic mode of action. One mechanism relates to the different ultimate cellular effects of activation of estrogen receptor (ER) α, promoting cell proliferation, and of ERβ, promoting apoptosis, with the major soy isoflavones genistein and daidzein activating especially ERβ. A second mode of action includes the role of epigenetics, including effects of isoflavones on DNA methylation, histone modification and miRNA expression patterns. The overview presented reveals that we are only at the start of unraveling the complex underlying mode of action for effects of isoflavones, both beneficial or adverse, on cell proliferation and cancer risks. It is evident that whatever model system will be applied, its relevance to human tissues with respect to ERα and ERβ levels, co-repressor and co-activator characteristics as well as its relevance to human exposure regimens, needs to be considered and defined.

Background: The present study was designed to analyse Web pages of German gynaecologists with regard to postmenopausal hormone therapy ( HT). There is a growing body of evidence, that the overall health risks of HT exceed the benefits. Making one's own informed choice has become a central concern for menopausal women. The Internet is an important source of health information, but the quality is often dubious. The study focused on the analysis of basic criteria such as last modi. cation date and quality of the HT information content. The results of the Women's Health Initiative Study (WHI) were used as a benchmark. Methods: We searched for relevant Web pages by entering a combination of key words (9 x 13 = 117) into the search engine www.google.de. Each Web page was analysed using a standardized questionnaire. The basic criteria and the quality of content on each Web page were separately categorized by two evaluators. Disagreements were resolved by discussion. Main Findings: Of the 97 websites identified, basic criteria were not met by the majority. For example, the modi. cation date was displayed by only 23 (23.7%) Web pages. The quality of content of most Web pages regarding HT was inaccurate and incomplete. Whilst only nine (9.3%) took up a balanced position, 66 (68%) recommended HT without any restrictions. In 22 cases the recommendation was indistinct and none of the sites refused HT. With regard to basic criteria, there was no difference between HT-recommending Web pages and sites with balanced position. Conclusion: Evidence-based information resulting from the WHI trial was insufficiently represented on gynaecologists' Web pages. Because of the growing number of consumers looking online for health information, the danger of obtaining harmful information has to be minimized. Web pages of gynaecologists do not appear to be recommendable for women because they do not provide recent evidence-based findings about HT.

The prevention of neurodegenerative dementias, such as Alzheimer's disease, is a public health priority. Due to the large numbers of affected patients, even interventions bringing about a relatively small delay in disease onset could have large public health effects. Randomized controlled trials (RCTs) are required to demonstrate the effectiveness of preventive interventions, but such trials raise specific methodological questions because they are new in the field of neurodegenerative diseases, and require large numbers of elderly subjects and lengthy follow-up periods. We performed a literature search to identify primary prevention RCTs for neurodegenerative dementia. The methodology of the trials was summarized and discussed during two expert meetings. Overall, 39 trials were identified that assessed dementia incidence or cognitive decline as a primary or secondary study outcome. Age was the most common selection criteria for target populations. Follow-up periods ranged from one month to nine years and were longest in studies measuring dementia incidence as an outcome. Results of RCTs have so far been generally negative and conflicting with those of observational studies, perhaps due to methodological issues. Future trials must therefore carefully consider the target population, outcomes and duration of follow-up to be used, and should assess the problem of attrition.