Evidence map›Paper›PMID 42142594›Full record

ReviewAgeing research reviews2026

17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.

Roberto Santín-Márquez, Michal Fornalik, Sean R Janovic, Jose V V Isola, Subhasri Biswas, Roshini Sathiaseelan, Jillian E J Cox, Sarah R Ocanas, Michael B Stout

Abstract readReview
In one paragraph

Review in Ageing research reviews, 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.

Roberto Santín-MárquezAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: roberto-santin-marquez@omrf.org.
Michal FornalikAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: michal-fornalik@omrf.org.
Sean R JanovicAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: sean-janovic@ouhsc.edu.
Jose V V IsolaAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: josevictor-isola@omrf.org.
Subhasri BiswasAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: subhasri-biswas@omrf.org.
Roshini SathiaseelanAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: roshini-sathiaseelan@omrf.org.
Jillian E J CoxNeuroscience Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. Electronic address: jillian-cox@ouhsc.edu.
Sarah R OcanasNeuroscience Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA. Electronic address: sarah-ocanas@omrf.org.
Michael B StoutAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA. Electronic address: michael-stout@omrf.org.

Funding

Role of estrogen receptor-a in aging and sex-specific responses to 17a-estradiolR01AG070035 · NIA · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI STOUT, MICHAEL B · 2021 to 2025
$2.6M
Sex chromosomal regulation of hippocampal microglial activation with Alzheimer's disease and agingDP5OD033443 · OD · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI OCANAS, SARAH RENEE · 2022 to 2025
$2.2M
A New Translational Rat Model for Evaluating Anti-Aging InterventionsR33AG072137 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI STEVEN N. AUSTAD, ARLAN G. RICHARDSON · 2024 to 2026
$2.2M
Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiolR00AG051661 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI STOUT, MICHAEL B · 2018 to 2020
$746k
NIA NIH HHS R00 AG051661NIA NIH HHS R01 AG070035NIA NIH HHS R33 AG072137NIH HHS DP5 OD033443
6 · The paper itself

Abstract

Estrogens are pleiotropic hormones that regulate reproductive and non-reproductive physiological processes in both sexes. Among these, 17α-estradiol (17α-E2), a C17 epimer of the canonical estrogen 17β-estradiol (17β-E2), has emerged as a promising modulator of aging and metabolism with sexual dimorphism. Unlike 17β-E2, which exerts broad estrogenic effects in both sexes, 17α-E2 extends lifespan and preferentially improves metabolic homeostasis in male mice while inducing only mild feminizing effects. Many of these benefits are mediated through estrogen receptor alpha (ERα). However, it remains unknown if its biological actions are mediated through genomic or nongenomic pathways and what the molecular basis is for male-biased efficacy. This review outlines evidence from preclinical models and translational studies, demonstrating that 17α-E2 mitigates age-related metabolic declines in males by reducing adiposity, enhancing insulin sensitivity, and preserving hepatic metabolic plasticity. Elucidating the sexually divergent actions of 17α-E2 can advance our understanding of sex-biased endocrine signaling and how these pathways modulate aging in a sex-specific manner.

Indexed as

AgingEstradiolEstrogensLongevitySex CharacteristicsAnimalsFemaleHumansMaleEstradiolEstrogens17α-estradiolAgingEstrogen receptorHealthspanLifespanMetabolismSex differences

Identifiers

PMID42142594
PMCPMC13570712

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.