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Effects of hormone therapy on depressive symptoms and cognitive functions in women with Alzheimer disease: a 12 month randomized, double-blind, placebo-controlled study of low-dose estradiol and norethisterone


Valen-Sendstad, Arnhild, Engedal, Knut, Stray-Pedersen, Babill, Strobel, Carsten, Barnett, Liv, Meyer, Nicolay, Nurminemi, Minna


The American Journal Of Geriatric Psychiatry: Official Journal Of The American Association For Geriatric Psychiatry, Volume: 18, No.: 1, Pages.: 11-20

Year of Publication



Objective: To elucidate the effects of low-dose 17beta-estradiol and norethisterone (hormone therapy [HT]) versus placebo in women with Alzheimer Disease (AD) on cognition, depressive symptoms, and activities of daily living.; Design: A 12-month randomized, double-blind, placebo-controlled study, stratified by apolipoprotein E (ApoE) genotype (with versus without the epsilon4 allele), duration of education (< or =9 versus >9 years), and age (< or =75 versus >75 years) performed during 2000-2004.; Setting: Ambulatory memory clinic in a general hospital.; Participants: Sixty-five female outpatients aged 65-89 years who met criteria for probable AD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition and International Classification of Diseases, tenth edition. Ten patients were excluded, resulting in 55 participants who had at least one posttreatment efficacy evaluation.; Intervention: Randomly assigned to receive either 1-mg estradiol and 0.5-mg norethisterone or placebo once daily.; Measurements: Cognitive variables were the Dementia Rating Scale, tests from Consortium to Establish a Registry for AD, Global Deterioration Scale (GDS) and Barthel Index.; Results: When only treatment effects were compared by analysis of variance, there were nonsignificant differences between treatment groups for all efficacy variables. A linear model analysis, including stratifying factors in addition to treatment in the model, revealed a significant main effect on mood. The depressive symptoms were lower in the HT group than in the placebo group. Those treated with HT without the ApoE epsilon4 allele had better mood, Word Learning Memory score, and GDS score. Those in the HT group with a higher level of education obtained a better GDS score. Adverse events did not differ between the groups.; Conclusion: HT interacts with ApoE genotype in women with AD. Women without an ApoE epsilon4 allele may get better mood and cognition with HT. HT may reduce depressive mood and give less cognitive decline.;

Bibtex Citation

@article{Valen_Sendstad_2010, doi = {10.1097/jgp.0b013e3181beaaf4}, url = {}, year = 2010, month = {jan}, publisher = {Elsevier {BV}}, volume = {18}, number = {1}, pages = {11--20}, author = {Arnhild Valen-Sendstad and Knut Engedal and Babill Stray-Pedersen and Carsten Strobel and Liv Barnett and Minna Nurminemi and Nicolay Meyer}, title = {Effects of Hormone Therapy on Depressive Symptoms and Cognitive Functions in Women With Alzheimer Disease: A 12 Month Randomized, Double-Blind, Placebo-Controlled Study of Low-Dose Estradiol and Norethisterone}, journal = {The American Journal of Geriatric Psychiatry} }


activities of daily living, administration & dosage, adverse effects, aged, 80 and over, alleles, alzheimer disease, apolipoproteins e, cognition, complications, depression, double-blind method, drug combinations, drug effects, drug therapy, estradiol, female, genetics, genotype, geriatric assessment, hormone replacement therapy, humans, norethindrone, placebos, psychiatric status rating scales, psychology, severity of illness index, treatment outcome

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

ADLs/IADLs, Cognition


Hospital Outpatient Care

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions