Evidence mapPaperPMID 41667737Full record

ArticleGeroScience2026

Low-dose tamoxifen ameliorates ovariectomy-induced metabolic and immune dysfunction.

Heather E McClurg, Amanda Ferraro, Gina Pham, Itzel Morales-Hernandez, Estefania Valencia-Rincon, Kevin D Pham, Willard M Freeman, Jacquelyn A Gorman, Marisol Castillo-Castrejon

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Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Heather E McClurgDepartment of Pathology, The University of Oklahoma College of Medicine, Biomedical Research Center, Room 458, 975 NE 10 Street, Oklahoma City, OK, 73104, USA.ORCID http://orcid.org/0009-0000-3932-2494
Amanda FerraroSection of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The University of Oklahoma College of Medicine, Oklahoma City, OK, USA.ORCID http://orcid.org/0000-0002-6626-0708
Gina PhamDepartment of Pathology, The University of Oklahoma College of Medicine, Biomedical Research Center, Room 458, 975 NE 10 Street, Oklahoma City, OK, 73104, USA.
Itzel Morales-HernandezDepartment of Pathology, The University of Oklahoma College of Medicine, Biomedical Research Center, Room 458, 975 NE 10 Street, Oklahoma City, OK, 73104, USA.
Estefania Valencia-RinconDepartment of Pathology, The University of Oklahoma College of Medicine, Biomedical Research Center, Room 458, 975 NE 10 Street, Oklahoma City, OK, 73104, USA.
Kevin D PhamGenes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Willard M FreemanGenes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Jacquelyn A GormanArthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Marisol Castillo-CastrejonDepartment of Pathology, The University of Oklahoma College of Medicine, Biomedical Research Center, Room 458, 975 NE 10 Street, Oklahoma City, OK, 73104, USA. marisol-castillocastrejon@ou.edu.ORCID https://orcid.org/0000-0003-0396-4908

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The decline in estrogen following menopause is a major driver of metabolic and immune dysfunction in aging females. While hormone replacement therapy improves many of these outcomes, its clinical use remains limited due to concerns regarding estrogen-sensitive malignancies. Tissue-selective estrogen complexes (TSECs), which combine estrogens with selective estrogen receptor modulators (SERMs) such as tamoxifen (TAM), represent a promising strategy to preserve the metabolic and immunological benefits of estrogen while reducing oncogenic risk. However, the systemic effects of TAM under conditions of estrogen deficiency remain incompletely defined. In this study, we investigated the metabolic and immunomodulatory actions of low-dose TAM, alone or in combination with 17β-estradiol (E2), in adult ovariectomized (OVX) female mice. OVX resulted in increased adiposity, hepatic steatosis, glucose intolerance, insulin resistance, immunoglobulin G3 (IgG3) concentration, and systemic inflammation, along with decreased immunoglobulin G1 (IgG1) concentration. E2, TAM, and E2 + TAM each attenuated OVX-induced adipose expansion, adipocyte hypertrophy, and proinflammatory cytokine production. TAM improved insulin sensitivity but did not fully restore glucose tolerance. Transcriptomic analysis of visceral adipose tissue-resident B cells revealed that E2 and E2 + TAM modulate overlapping yet distinct immune-regulatory networks, including suppression of pro-inflammatory signaling, regulation of immune checkpoints, and genes linked to adipose homeostasis. Low-dose TAM emerges as a modulator of estrogen receptor signaling that attenuates multiple features of OVX-induced metabolic and inflammatory dysfunction, though its limited effect on glycemic control highlights the need for tissue-specific evaluation of SERM-based interventions. These findings provide mechanistic insight into endocrine-immune-metabolic interactions and inform strategies to reduce aging-related disease risk in postmenopausal women.

Indexed as

Adipose tissueB cellsEstrogenInflammationMenopause

Identifiers

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Registered trials

None linked

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 Socratic graph.