Published Papers
Estrogen receptor β in astrocytes modulates cognitive function in mid‑age female mice
By Noriko Itoh et al. (Nature Communications, Sep 2023)
This study demonstrates that the loss of ovarian hormones in mid‑life female mice—but not young ones—leads to hippocampal atrophy and cognitive impairment. The authors show that estrogen receptor β (ERβ) expressed in astrocytes is critical for maintaining hippocampal structure and function, suggesting an age-dependent mechanism for neuroprotection.
The X Factor in Neurodegeneration
By Rhonda Voskuhl & Yuichiro Itoh (Journal of Experimental Medicine, Dec 2022)
This review explores how sex chromosome-linked mechanisms and declining sex hormones contribute to differences in neurodegeneration between men and women. The paper highlights the importance of tailoring neuroprotective strategies based on sex-specific biology.
Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis
By Rhonda R. Voskuhl et al. (Proceedings of the National Academy of Sciences, May 2019)
In this study, the authors performed transcriptomic analysis of oligodendrocytes during remyelination in mouse models of MS, uncovering that regulation of cholesterol synthesis genes is essential for repair—making cholesterol homeostasis a promising target for therapeutic intervention.
Decreased neurofilament light chain levels in estriol‑treated multiple sclerosis
By Rhonda R. Voskuhl et al. (Annals of Clinical & Translational Neurology, Aug 2022)
This clinical study shows that women with relapsing‑remitting MS treated with estriol had significantly reduced serum neurofilament light chain—a biomarker of neurodegeneration—compared to placebo. These results support the neuroprotective effect of estriol in MS management.
Estriol‑mediated neuroprotection in multiple sclerosis localized by voxel‑based morphometry
By Allan MacKenzie‑Graham et al. (Brain & Behavior, Sep 2018)
Voxel-based morphometry analysis revealed that estriol treatment in women with MS preserved gray matter in specific cortical regions, correlating with improvements in cognitive testing (PASAT). This provides compelling imaging evidence of estriol’s neuroprotective impact.
Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomized, placebo‑controlled, phase 2 trial
A landmark 2016 study published in The Lancet Neurology, co-authored by Dr. Rhonda Voskuhl, confirmed that adding estriol to an MS treatment protocol significantly improved cognitive outcomes and disease progression compared to placebo. The trial demonstrated both safety and efficacy in addressing relapse frequency and neural protection.
Oestrogen receptor β‑ligand acts on CD11c⁺ cells to mediate protection in experimental autoimmune encephalomyelitis
This 2017 paper in Brain explores the mechanism by which ERβ‑ligands protect immune cells (CD11c⁺) in experimental models of MS. The findings reveal how estriol’s interaction with these receptors helps reduce inflammation and neuropathology in the CNS.
Neuroprotection in cerebral cortex induced by the pregnancy hormone estriol
Published in Laboratory Investigation (August 2023)
This study shows that estriol—used in PearlPAK—preserves cortical neurons and synaptic function in preclinical models, offering strong evidence for its role in cognitive preservation.
Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease
This 2012 research demonstrates that estriol helps maintain synaptic function in the hippocampus during autoimmune challenges, reinforcing its therapeutic potential for memory and cognitive stability.
Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis
Published in the Journal of Neuroscience (July 2012)
This paper found that estriol treatment reduces gray matter loss in preclinical MS models—offering a neuroprotective effect critical to cognitive resilience.
Treatment of multiple sclerosis with the pregnancy hormone estriol
This foundational study from Annals of Neurology (October 2002) was one of the first to report estriol’s potential as a safe, effective adjunctive treatment for MS, laying the groundwork for later cognitive-focused trials.