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Estrogen metabolites and hydrogen peroxide - Missing elements in the pathophysiology and possible treatment of

Zofia Winczewska1, Agnieszka Mechlińska2, Piotr Radziwiłłowicz2

  • 1Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.

Redox Biology
|March 11, 2025
PubMed

Insights

Estrogen metabolism imbalances and elevated hydrogen peroxide (H2O2) are linked to treatment-resistant depression (TRD). Reduced estrogen metabolites may contribute to oxidative stress in TRD pathogenesis.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Biochemistry

Background:

  • Depression pathogenesis is complex and management remains challenging.
  • Novel therapeutic strategies and mechanisms for treatment-resistant depression (TRD) are needed.

Purpose of the Study:

  • To investigate the role of estrogen metabolites in TRD pathogenesis.
  • To determine concentrations of estrogens, their metabolites, and hydrogen peroxide (H2O2) in TRD patients.

Main Methods:

  • Measurement of estrogen and metabolite concentrations in biological samples from TRD patients.
  • Quantification of hydrogen peroxide (H2O2) levels in the same patient cohort.

Main Results:

  • First-time observed association between unbalanced estrogen metabolism and elevated H2O2 in TRD.
  • Reduced concentrations of 2-methoxyestradiol (2-ME2), 17α-estradiol (α-E2), and 17β-estradiol (β-E2) noted.
  • Abnormal estrogen metabolism may lead to neurotoxic semiquinones and quinones.

Conclusions:

  • Unbalanced estrogen metabolism and increased oxidative stress are implicated in TRD.
  • Potential novel mechanism involving neurotoxic metabolites contributing to oxidative stress in TRD identified.
Keywords:
2-MethoxyestradiolHydrogen peroxideOxidative stressQuinonesReactive oxygen speciesTreatment resistant depression

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