TY - JOUR
T1 - Association between menopausal hormone therapy and risk of neurodegenerative diseases
T2 - Implications for precision hormone therapy
AU - Kim, Yu Jin
AU - Soto, Maira
AU - Branigan, Gregory L.
AU - Rodgers, Kathleen
AU - Brinton, Roberta Diaz
N1 - Funding Information:
This study was supported by grants from the Women's Alzheimer's Movement and National Institute on Aging grants P01AG026572 (Perimenopause in Brain Aging and Alzheimer's Disease), R37AG053589 (Aging and Estrogenic Control of the Bioenergetic System in Brain), and T32AG061897 (Translational Research in Alzheimer's Disease and Related Dementias [TRADD]) to Brinton. The National Institutes of Health and the Women's Alzheimer's Movement Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
Dr. Brinton reported receiving grants from the Women's Alzheimer's Movement and the National Institute on Aging during the conduct of the study. No other disclosures were reported.
Funding Information:
This study was supported by grants from the Women's Alzheimer's Movement and National Institute on Aging grants P01AG026572 (Perimenopause in Brain Aging and Alzheimer's Disease), R37AG053589 (Aging and Estrogenic Control of the Bioenergetic System in Brain), and T32AG061897 (Translational Research in Alzheimer's Disease and Related Dementias [TRADD]) to Brinton. The National Institutes of Health and the Women's Alzheimer's Movement Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
PY - 2021
Y1 - 2021
N2 - Introduction: The impact of menopausal hormone therapy (HT) on age-associated Alzheimer's and neurodegenerative diseases (NDDs) remains unresolved. To determine the effect of HT, formulation, type, and duration on risk of NDDs, a retrospective analysis was performed using a 10-year Humana claims dataset. Methods: Study population included women aged 45 years or older with or without claim records of HT medications. Patients diagnosed with NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), dementia, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) were identified. Relative risk (RR) ratios and 95% confidence intervals (CI) for combined NDDs, or AD, PD, dementia, MS, and ALS were determined. Cumulative hazard ratios were determined to investigate the association between HT and NDDs at different age groups. Results: In 379,352 women with or without claim records of HT, use of HT was associated with significantly reduced risk for combined NDDs (RR 0.42, 95% CI 0.40–0.43, P < 0.001). Average follow-up time was 5.1 [2.3] years. Formulations containing natural steroids 17β-estradiol and/or progesterone were associated with greater reduction in NDD risk. Oral- HT users showed significantly reduced RRs (0.42, 0.41–0.44, P < 0.001) for combined NDDs compared to non-HT users. The RRs for transdermal-HT users were significantly decreased for all-cause dementia (0.73, 0.60–0.88, P = 0.001) and MS (0.55, 0.36–0.84, P = 0.005). Greatest reduction in risk of NDD, AD, and dementia emerged in patients aged 65 years or older. Further, the protective effect of long-term therapy (>1 year) on combined NDDs, AD, PD, and dementia was greater compared to short-term therapy (≤1 year). Discussion: HT was associated with reduced risk of all NDDs including AD and dementia, with greater duration of therapy and natural steroid formulations associated with greater efficacy. These findings advance precision HT to prevent NDDs including AD.
AB - Introduction: The impact of menopausal hormone therapy (HT) on age-associated Alzheimer's and neurodegenerative diseases (NDDs) remains unresolved. To determine the effect of HT, formulation, type, and duration on risk of NDDs, a retrospective analysis was performed using a 10-year Humana claims dataset. Methods: Study population included women aged 45 years or older with or without claim records of HT medications. Patients diagnosed with NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), dementia, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) were identified. Relative risk (RR) ratios and 95% confidence intervals (CI) for combined NDDs, or AD, PD, dementia, MS, and ALS were determined. Cumulative hazard ratios were determined to investigate the association between HT and NDDs at different age groups. Results: In 379,352 women with or without claim records of HT, use of HT was associated with significantly reduced risk for combined NDDs (RR 0.42, 95% CI 0.40–0.43, P < 0.001). Average follow-up time was 5.1 [2.3] years. Formulations containing natural steroids 17β-estradiol and/or progesterone were associated with greater reduction in NDD risk. Oral- HT users showed significantly reduced RRs (0.42, 0.41–0.44, P < 0.001) for combined NDDs compared to non-HT users. The RRs for transdermal-HT users were significantly decreased for all-cause dementia (0.73, 0.60–0.88, P = 0.001) and MS (0.55, 0.36–0.84, P = 0.005). Greatest reduction in risk of NDD, AD, and dementia emerged in patients aged 65 years or older. Further, the protective effect of long-term therapy (>1 year) on combined NDDs, AD, PD, and dementia was greater compared to short-term therapy (≤1 year). Discussion: HT was associated with reduced risk of all NDDs including AD and dementia, with greater duration of therapy and natural steroid formulations associated with greater efficacy. These findings advance precision HT to prevent NDDs including AD.
KW - Alzheimer's disease
KW - age-associated neurodegenerative diseases
KW - dementia
KW - estrogen
KW - menopausal hormone therapy
KW - precision hormone therapy
KW - progestin
KW - retrospective analysis
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U2 - 10.1002/trc2.12174
DO - 10.1002/trc2.12174
M3 - Article
AN - SCOPUS:85112197479
SN - 2352-8737
VL - 7
JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions
JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions
IS - 1
M1 - e12174
ER -