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Research Article
September 2, 2022
continuing medical educationeditorialLetter to the Editor

Use of Hormone Replacement Therapy and Risk of Dementia
A Nationwide Cohort Study

October 25, 2022 issue
99 (17) e1835-e1842
Letters to the Editor

Abstract

Background and Objectives

Estrogen has the potential to influence brain physiology implicated in dementia pathogenesis. Hormone replacement therapy (HRT) might be expected to influence the risk of dementia. Observational data indicated that HRT was associated with reductions in dementia risk, but experimental evidence demonstrates that HRT increases the incidence of dementia. To determine the effect of HRT on the risk of dementia, a retrospective cohort study was performed using a nationwide claims dataset in Taiwan.

Methods

A population-based longitudinal study was performed using data from the Longitudinal Health Insurance Database in Taiwan. A total of 35,024 women with HRT were enrolled as the exposed cohort and 70,048 women without HRT were selected on the basis of propensity matching as the comparison cohort. All participants were followed up until the diagnosis of dementia, death, or at the end of December 31, 2013, whichever occurred first. Overall, the average duration of follow-up (±SD) in the HRT and comparison cohorts was 12.3 (±2.3) and 12.2 (±2.4), respectively. The Cox proportional hazards regression models were conducted to produce hazard ratios (HRs) with 95% CIs to evaluate the association of HRT with the risk of dementia.

Results

In the follow-up period, the cumulative incidence of dementia for the HRT cohort (20.04 per 1,000) was significantly higher than the corresponding cumulative incidence for the comparison cohort (15.79 per 1,000), resulting in an adjusted HR of 1.35 (95% CI 1.13–2.62). There was an increased risk of dementia with a higher cumulative dose of HRT prescription (p for trend <0.0001).

Discussion

This cohort study documented that HRT was associated with an increased risk of dementia. The clinical implications of this study merit further investigations.

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Letters to the Editor
6 November 2022
Reader Response: Use of Hormone Replacement Therapy and Risk of Dementia
Joseph S. Jeret, MD, FAAN | Icahn School of Medicine

I read this article by Dr. Sung et al. with interest.1 After screening 522,350 women, 150,623 met selection criteria. The authors identified 702 patients with dementia confirmed by ICD-9-CM coding by a board-certified neurologist or psychiatrist. However, the study includes several serious methodological flaws.

Of the 702 women in the study, over 77% were classified not as Alzheimer’s or vascular dementia patients (the two most common causes of dementia), but as other. In the comparison cohort, other dementia was diagnosed 75.8% of the time. It is disappointing that the authors could not reach a diagnosis for some three-quarters of their patients. If these individuals had AIDS, Huntington’s, or neurosyphilis, it would change the conclusion.

Further, the causes of Alzheimer’s and vascular dementia are quite different. To lump them together is illogical. To combine this group of 77% without a specific etiology compounds the problem.

In addition, the use of ergoloid mesylates and ginko were sufficient to be included in the diagnosis of dementia. Use of these products does not prove a diagnosis of dementia. In summary, these data are interesting, but of little use in clinical decision making. I would be interested to see a more complete study after the authors personally review the 542 charts of patients with "other" dementia.

Disclosure

The author reports no relevant disclosures. Contact [email protected] for full disclosures.  

References

  1. Sung YF, Tsai CT, Kuo CY, et al. Use of Hormone Replacement Therapy and Risk of Dementia: A Nationwide Cohort Study [published online ahead of print, 2022 Sep 2]. Neurology. 2022;10.1212/WNL.0000000000200960.

Information & Authors

Information

Published In

Neurology®
Volume 99Number 17October 25, 2022
Pages: e1835-e1842

Publication History

Received: December 4, 2021
Accepted: May 25, 2022
Published online: September 2, 2022
Published in print: October 25, 2022

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Disclosure

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Study Funding

This study was funded by Tri-Service General Hospital (TSGH-C103-085 and TSGH-C104-085).

Authors

Affiliations & Disclosures

Yueh-Feng Sung, MD, PhD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Chun-Teng Tsai, MS
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Cheng-Yi Kuo, PhD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jiunn-Tay Lee, MD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Chung-Hsing Chou, MD, PhD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Yong-Chen Chen, PhD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Yu-Ching Chou, PhD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Chien-An Sun, ScD
From the Department of Neurology (Y.-F.S., J.-T.L., C.-H.C.), Tri-Service General Hospital, School of Public Health (C.-T.T., Y.-C. Chou), Department and Graduate Institute of Biology and Anatomy (C.-Y.K.), and Graduate Institute of Medical Sciences (C.-H.C.), National Defense Medical Center; Department of Medicine (Y.-C. Chen), Data Science Center (Y.-C. Chen, C.-A.S.), and Department of Public Health (C.-A.S.), College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Sun [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.

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