Timing of hormone therapy and dementia: The critical window theory revisited
- 12 November 2010
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 69 (1), 163-169
- https://doi.org/10.1002/ana.22239
Abstract
Objective: Although previous research has shown that initiation of postmenopausal estrogen hormone therapy (HT) in late life increases risk of dementia, animal studies and some observational studies have suggested that midlife use of HT may be beneficial; however, this has not been rigorously investigated in large population‐based studies. Our objective was to compare HT use in midlife with that in late life on risk of dementia among 5,504 postmenopausal female members of an integrated healthcare delivery system. Methods: HT use was determined at midlife (mean age, 48.7 years) from a survey in 1964 and in late life (mean age, 76 years) using pharmacy databases from 1994 to 1998. Risk of dementia diagnosis was evaluated with inpatient and outpatient diagnoses made in Neurology, Neuropsychology, and Internal Medicine from 1999 to 2008. Cox proportional hazard models were used to examine effects of HT use at different times on dementia risk with adjustment for age, education, race, body mass index, number of children, and comorbidities. Results: A total of 1,524 women (27%) were diagnosed with dementia during the follow‐up period. Compared to women never on HT, those taking HT only at midlife had a 26% decreased risk (multivariate adjusted hazards ratio [aHR], 0.74; 95% confidence interval [CI], 0.58–0.94 ), whereas those taking HT only in late life had a 48% increased risk (aHR, 1.48; 95% CI, 1.10–1.98), and women taking HT at both mid and late life had a similar risk of dementia (aHR, 1.02; 95% CI, 0.78–1.34 ). Interpretation: These findings suggest that use of HT in midlife only may protect against cognitive impairment, whereas HT initiation in late life could have deleterious effects. ANN NEUROL, 2010Keywords
This publication has 22 references indexed in Scilit:
- Incidence of Dementia in Long-term Hormone UsersAmerican Journal of Epidemiology, 2007
- Oestrogens and the Structural and Functional Plasticity of Neurons: Implications for Memory, Ageing and Neurodegenerative ProcessesCiba Foundation symposium, 2007
- The Critical Period Hypothesis: Can It Explain Discrepancies in the Oestrogen‐Cognition Literature?Journal of Neuroendocrinology, 2006
- Estrogen and memory in women: how can we reconcile the findings?Hormones and Behavior, 2005
- Postmenopausal hormone therapy and Alzheimer's disease risk: interaction with ageJournal of Neurology, Neurosurgery & Psychiatry, 2005
- CNS: Sex Steroids and SERMsAnnals of the New York Academy of Sciences, 2003
- Determinants of long-term hormone replacement therapy and reasons for early discontinuationObstetrics & Gynecology, 2000
- Estrogen and Nerve Growth Factor‐related Systems in BrainAnnals of the New York Academy of Sciences, 1994
- Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology.American Journal of Public Health, 1992
- Automated Multiphasic Screening and DiagnosisAmerican Journal of Public Health and the Nations Health, 1964