The Effect of Estrogen Replacement Therapy on Alzheimer's Disease and Parkinson's Disease in Postmenopausal Women: A Meta-Analysis

Abstract

Background: Estrogen replacement therapy (ERT) is a common treatment method for menopausal syndrome; however, its therapeutic value for the treatment of neurological diseases is still unclear. Epidemiological studies were performed, and the effect of postmenopausal ERT on treating neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), was summarized through a meta-analysis. Methods: Twenty-one articles were selected using a systematic searching of the contents listed on PubMed and Web of Science before June 1, 2019. Epidemiological studies were extracted, and relevant research data were obtained from the original articles based on the predefined inclusion criteria and data screening principles. The Comprehensive Meta-Analysis Version 2 software was used to pool effective size, test heterogeneity, conduct meta-regression and subgroup analysis, and to calculate publication bias. Results: Our results showed that ERT significantly decreased the risk of onset and/or development of AD [odds ratio (OR): 0.672; 95% CI: 0.581-0.779; P < 0.001] and PD (OR: 0.470; 95% CI: 0.368-0.600; P < 0.001) compared with the control group. A subgroup and meta-regression analysis showed that study design and measure of effect were the source of heterogeneity. Age, sample size, hormone therapy ascertainment, duration of the treatment, or route of administration did not play a significant role in affecting the outcome of the meta-analysis. Conclusion: We presented evidence here to support the use of estrogen therapy for the treatment of AD and PD.

Keywords: Alzheimer's disease; Parkinson's disease; estrogen replacement therapy; meta-analysis; systematic review.

Figure 1

Flowchart describing the approach used to identify eligible studies. We conducted a systematic search on Medline (via PubMed and Web of Science) and covering all articles up until June 1, 2019.

Figure 2

Forest plot displaying random-effects meta-analysis results for the association between Alzheimer's disease (AD) (A) and Parkinson's disease (PD) (B) and estrogen replacement therapy (ERT).

Figure 3

The following subgroups were defined in the Alzheimer's disease (AD) group: case >500 vs. case ≤500,case-control study vs. prospective cohort, publish year ≤ 1995 vs. 1996–2005 vs. 2006–2019, women age ≤70 vs. 71–79 vs. age ≥80, measure of effect = odds ratio (OR) vs. hazard ratio (HR) vs. relative risk (RR), hormone therapy ascertainment by interview vs. questionnaires vs. prescription database vs. medical records, duration of the treatment <5 years vs. 5–10 years vs. treatment >10 years.

Figure 4

Forest plot displaying random-effects meta-analysis results for the impact of different research types, which were case-control study (A) and prospective cohort (B).

Figure 5

The outcome of the sensitivity analysis in Alzheimer's disease (AD) (A) and Parkinson's disease (PD) (B), with the exclusion of one study.

Figure 6

The funnel plot was symmetrical in Alzheimer's disease (AD) (A) and Parkinson's disease (PD) (B), suggesting that there was no publication bias in the current analysis.