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September 5, 2026MetabolitesOpen Access

Estrogen degradation metabolites induce cardiac hypertrophy and fibrosis by increasing oxidative stress.

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Why the study?

Although views on estrogen degradation metabolites (EDMs) have changed, unknowns remain regarding their effects on the heart after findings showed they affect isolated cardiac mitochondria.

Population

Rat H9c2 cardiomyoblast cells and intact and oophorectomized female rats

Comparison

Exposure to Met A (2-hydroxyestrone) vs Met D (17β-estradiol-3-methyl-ether)

Design

In vitro and in vivo animal experimental study

Key result

Exposure to estrogen degradation metabolites, particularly Met D, significantly decreased antioxidant capacity and increased oxidative stress, leading to cardiac hypertrophy and fibrosis.

Authors

ASAlejandro Silva‐PalaciosGNGabriela Navarrete-AnastasioELElizabeth Lira‐Silva

Discussion

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Overview

Met D may promote oxidative stress, hypertrophy, and fibrosis in estrogen-deficient rat hearts despite preserved function; leaves open human relevance and requires prospective study.

Key Points

  • To evaluate the in vitro cellular effects and in vivo cardiac impact of two estrogen degradation metabolites, 2-hydroxyestrone (Met A) and 17β-estradiol-3-methyl-ether (Met D), in cardiac cells and oophorectomized female rats.
  • Exposed rat H9c2 cardiomyoblast cells to varying concentrations and durations of Met A and Met D to evaluate cell viability, mitochondrial membrane potential, and oxidative stress.
  • Administered Met A and Met D to intact and oophorectomized (Oopho) female rats to assess heart function via echocardiography, histological tissue remodeling, and markers of cardiac oxidative damage.
  • Met D induced the most pronounced adverse cellular effects in vitro, significantly reducing antioxidant capacity while elevating oxidative stress.
  • Echocardiographic assessments showed unchanged global cardiac pump function across animal groups, but histological analyses revealed clear signs of cardiac hypertrophy and fibrosis.

Structured PICO

P
Population
Female rats (intact and oophorectomized) and rat H9c2 cardiomyoblast cells exposed to estrogen degradation metabolites.
I
Intervention
Exposure to two exogenous estrogenic metabolites (EDMs): Met A (2-hydroxyestrone) and Met D (17β-estradiol-3-methyl-ether)
C
Comparator
Control (unexposed cells/rats)
O
Outcome
Cell viability, mitochondrial potential, and oxidative stress in H9c2 cells; echocardiographic analyses, histological analyses, cardiac damage, and oxidative stress in intact and Oopho ratssurrogate

Exogenous estrogenic metabolites, particularly 17β-estradiol-3-methyl-ether, induce oxidative stress, cardiac hypertrophy, and fibrosis in female rat models without altering echocardiographic cardiac function.

Cite This Study

Silva‐Palacios et al. (2026) studied this question. Estrogen degradation metabolites (Met A and Met D) was evaluated on Cell viability, mitochondrial potential, oxidative stress, and cardiac function/histology. Exposure to estrogen degradation metabolites, particularly Met D, significantly decreased antioxidant capacity and increased oxidative stress, leading to cardiac hypertrophy and fibrosis.

synapsesocial.com/papers/6a9bd48c6b95aff0620ec3f2https://doi.org/10.3390/metabo16090647
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Estrogen Degradation Metabolites: Some Effects on Heart Mitochondria2025
  2. 22-Methoxyestradiol ameliorates doxorubicin-induced cardiotoxicity by regulating the expression of GLUT4 and CPT-1B in female rats2024 · 3 citations
  3. 3Abstract Thu156: Impacts of Estradiol and Progesterone On Cardiomyocyte Cell Dynamics and Mitochondrial Respiration2025
  4. 4Effect of catecholestrogen administration during adriamycin-induced cardiomyopathy in ovariectomized rat2005 · 13 citations
  5. 5Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability2014 · 32 citations