Trial reportJournal of Alzheimer's disease : JAD2016
Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition.
Trial report in Journal of Alzheimer's disease : JAD, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.Frontiers in endocrinology · 2024Pooled it
- Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.Frontiers in aging neuroscience · 2023Pooled it
- Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study.PLoS medicine · 2024Trial
- Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy.Maturitas · 2023Trial
- Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Trial
- Lessons from KEEPS: the Kronos Early Estrogen Prevention Study.Climacteric : the journal of the International Menopause Society · 2021Trial
- Sleep quality and cortical amyloid-β deposition in postmenopausal women of the Kronos early estrogen prevention study.Neuroreport · 2021Trial
- Effect of menopausal hormone therapy on proteins associated with senescence and inflammation.Physiological reports · 2020Trial
- Menopausal hormone therapy, blood thrombogenicity, and development of white matter hyperintensities in women of the Kronos Early Estrogen Prevention Study.Menopause (New York, N.Y.) · 2020Trial
- Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Trial
- Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.Neurology · 2018Trial
- Estradiol and memory circuitry in the postmenopause: Modification by APOE4.Research square · 2026Article
- Estrogen Withdrawal-Induced Cognitive Impairment in Menopausal Women: Mechanisms and Prospects for Integrated Interventions.International journal of molecular sciences · 2026Review
- Evidence of APOE4-related brain vulnerabilities in verbal memory systems in midlife women.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE4 negates the effects of ovarian hormones on cerebrovascular endothelial and mitochondrial function.The Journal of physiology · 2026Article
- Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Estradiol ameliorates AD pathology and cognitive deficits by SORLA-mediated APP endosomal trafficking.Alzheimer's research & therapy · 2026Article
- Women's midlife: the front line of Alzheimer prevention.The Journal of clinical investigation · 2026Review
- Menopausal hormone therapy and risk of neuropsychiatric disease: a drug target Mendelian randomisation study.npj women's health · 2026Article
- Development and Implementation of a Radiation Safety Screening Protocol for a Clinical Study Using Amyloid Positron Emission Tomography Imaging.Ochsner journal · 2026Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIt remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer's disease (AD).
objectiveTo investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women.
methodsParticipants within 5-36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated.
resultsWomen (age = 52-65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11-0.83)]. In the APOEɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004-0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006-0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOEɛ4 non-carriers.
conclusionIn this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOEɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.