Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics

Area of Science:

• Neurology
• Endocrinology
• Immunology

Background:

• Multiple sclerosis (MS) treatment faces challenges in neuroprotection and remyelination.
• Sexual hormones, particularly estrogens and testosterone, are being investigated for their therapeutic potential in MS.
• Observed differences in MS activity between sexes suggest a role for these hormones.

Purpose of the Study:

• To review the therapeutic effects of testosterone and estrogens in the context of multiple sclerosis.
• To evaluate the potential of these hormones in neuroprotection and remyelination.

Main Methods:

• Review of existing literature on testosterone and estrogen effects in MS.
• Examination of preclinical data (neuron cultures, experimental autoimmune encephalomyelitis model).
• Analysis of clinical trial data, specifically for estriol therapy.

Main Results:

• Both testosterone and estrogens exhibit anti-inflammatory effects.
• Testosterone protects neurons and promotes myelin repair via androgen receptors.
• Estrogens reduce central nervous system inflammation (ERα) and aid myelin/axon repair (ERβ).
• Estriol therapy in Phase 2 trials decreased MS clinical activity and MRI inflammatory markers.

Conclusions:

• Estriol shows significant therapeutic potential as an add-on therapy for MS, warranting Phase 3 trials.
• Testosterone is a candidate for Phase 2 trials, requiring more evidence for its efficacy.
• Hormone therapy should be considered as an adjunctive treatment for MS.
• Development of new tools is crucial for assessing hormone effects on neuroprotection and remyelination.