Role of Estrogen in The Treatment of Multiple Sclerosis; Novel Insights Regarding Its Mechanism of Action | ||
| Archives of Pharmaceutical Sciences Ain Shams University | ||
| Articles in Press, Accepted Manuscript, Available Online from 11 October 2025 PDF (1.26 M) | ||
| Document Type: Review Article | ||
| DOI: 10.21608/aps.2025.332157.1204 | ||
| Authors | ||
| Menna Ibrahim* 1; Amany Mohamed Gad2, 3; Esther Tharwat4; Mariane G Tadros5 | ||
| 1General Administration for Regulation of Marketing and Advertising Materials, Egyptian Drug Authority (EDA), Cairo, Egypt | ||
| 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, Kantara 41636, Egypt | ||
| 3Department of Pharmacology and Toxicology, Egyptian Drug Authority (EDA) - Formerly National Organization for Drug Control and Research (NODCAR), Giza, 12654, Egypt | ||
| 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain shams University, Cairo, Egypt | ||
| 5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt | ||
| Abstract | ||
| Multiple sclerosis (MS) is a long-term illness predominantly affecting young adults, characterized by chronic inflammation and neurodegeneration as well as autoimmune responses. It causes various neurological symptoms including vision problems, motor dysfunction, and cognitive impairment. MS arises from a complex interplay between genetic susceptibility and environmental influences, leading to an aberrant immune response against myelin. Microglial activation and the production of inflammatory mediators, such as cytokines and reactive oxygen species (ROS), contribute to myelin damage and axonal loss. MS occurs more frequently in females than males. This fact draws attention to the hormonal role of estrogen in the pathology and disease progression. Besides estrogen's role in regulating the menstrual cycle and pregnancy, it binds to specific receptors and activates intracellular signaling pathways. It generally shifts T-helper lymphocytes -1 (Th-1) type cellular immunity into Th-2 humoral immunity with the help of regulatory T cells (T-reg). Additionally, it halts the production of inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Recent studies have explored the potential therapeutic, neuroprotective, and immunomodulatory roles of estrogen in MS. Estriol, a specific form of estrogen, has shown promise in reducing relapse rates in relapsing-remitting MS (RRMS) patients. Clinical trials have demonstrated that estradiol, when used alongside standard MS therapies, can significantly reduce relapse frequency and improve neurological function. Understanding the intricate relationship between estrogen and MS pathogenesis can yield crucial insights for developing novel innovative therapeutic approaches. By targeting estrogen-related pathways, researchers aim to develop protective and therapeutic agents to combat MS progression. | ||
| Keywords | ||
| Multiple sclerosis; Inflammation; Oxidative stress; Estrogen; TNF-α | ||
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