What is the role of estriol in neuroprotection for multiple sclerosis patients?

Estriol and Neuroprotection in Multiple Sclerosis: Key Peer-Reviewed Articles

The most recent evidence strongly supports estriol's neuroprotective effects in multiple sclerosis, with the 2023 laboratory investigation demonstrating that estriol treatment reduces cerebral cortex atrophy, increases remyelination, and preserves neurons and synapses in MS models. 1

Key Articles on Estriol and Neuroprotection in MS

Neuroprotective Mechanisms

• Cerebral Cortex Neuroprotection (2023): The most recent and comprehensive laboratory investigation demonstrated that estriol treatment:

  • Decreased cerebral cortex atrophy
  • Increased cholesterol synthesis proteins in oligodendrocytes
  • Promoted formation of remyelinating oligodendrocytes
  • Increased myelin in treated EAE mice
  • Preserved cortical layer V pyramidal neurons and their apical dendrites
  • Protected synapses from degradation 1

• Neurofilament Light Chain Reduction (2022):

  • Oral estriol treatment (8 mg dose) reduced serum neurofilament light chain levels in non-pregnant MS women
  • This reduction indicates protection from neuro-axonal injury
  • Supports estriol's neuroprotective effects at the molecular level 2

Clinical Evidence

• Estriol with Glatiramer Acetate (2016):
  • Randomized, double-blind, placebo-controlled phase 2 trial
  • Estriol (8 mg daily) combined with glatiramer acetate reduced annualized relapse rate (0.25 vs 0.37 in placebo group)
  • Adjusted rate ratio: 0.63 (95% CI 0.37-1.05; p=0.077)
  • Treatment was well-tolerated over 24 months 3

Mechanistic Insights

• Estrogen Receptor Beta Pathway (2017):

  • Estriol binds to estrogen receptor (ER) beta
  • ER beta ligand treatment was protective in experimental autoimmune encephalomyelitis (EAE) models
  • Protection observed across both sexes and genetic backgrounds
  • Longitudinal MRIs showed decreased brain atrophy in cerebral cortex gray matter and cerebellum
  • Spared myelin, axons, neurons, and synapses 4

• Early Research Foundation (2009):

  • Initial evidence supporting estriol's dual mechanisms:
    • Immunomodulatory effects
    • Direct neuroprotective pathways
  • Early pilot trials showed encouraging results 5

Clinical Implications

• The 8 mg daily oral estriol dose appears optimal as it:

  • Induces mid-pregnancy blood estriol levels
  • Shows measurable neuroprotective effects
  • Has acceptable safety profile 2, 3

• Potential side effects to monitor:

  • Irregular menses (more common with estriol)
  • Vaginal infections (less common with estriol) 3

• No significant concerns observed regarding:

  • Breast fibrocystic disease
  • Uterine fibroids
  • Endometrial lining thickness 3

Research Gaps and Future Directions

• Phase 3 trials are warranted to confirm efficacy and safety
• Further investigation of ER beta ligands as "next generation estriol" treatments
• Additional research on optimal timing and duration of treatment
• Exploration of combination therapies with other disease-modifying treatments

The evidence consistently demonstrates estriol's neuroprotective potential in MS through multiple mechanisms, with the most recent research providing the strongest support for its ability to preserve neural structures and promote remyelination.