ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2024
Sex hormones and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study.
Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Demyelinating disorders in women: epidemiology, immunology, and clinical implications across MS, NMOSD, and MOGAD.Journal of neurology · 2026Review
- AQP4-IgG-Induced Astrocyte-Derived Small Extracellular Vesicles Carrying Mitochondrial DNA Regulate the TLR9/MyD88/NF-κB Pathway to Drive Microglial Activation and Neuromyelitis Optica.Neurochemical research · 2026Article
- Beyond the optic disc: Investigating gender-based differences in optic neuritis.World journal of clinical cases · 2025Review
- Article
- Brain volumetry and spinal cord imaging in patients with AQP4-IgG+ NMOSD-a systematic review and meta-analysis.Therapeutic advances in neurological disorders · 2025Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
backgroundFemales are considered to have an increased susceptibility to neuromyelitis optica spectrum disorder (NMOSD) than males, especially aquaporin-4 (AQP4) antibody positive NMOSD, indicating that sex hormones may be involved in the NMOSD pathogenesis. However, the causality between sex hormones and NMOSD still remains unclear.
methodsBased on the genome-wide association study (GWAS) data of three sex hormones (estradiol (E2), progesterone (PROG) and bioavailable testosterone (BAT)), sex hormone-binding globulin (SHBG), age of menarche, age of menopause, and NMOSD (total, AQP4 + and AQP4 -), we performed a two-sample bidirectional Mendelian randomization (MR) study. Sex-stratified GWAS data of E2, PROG, BAT, and SHBG was obtained for gender-specific MR analysis. Causal inferences were based on the inverse variance weighted method, MR-Egger regression, and weighted median method. The reverse MR analysis was also performed to assess the impact of NMOSD on hormone levels.
resultsPROG in females had aggravative effects on NMOSD (P < 0.001), especially AQP4 - NMOSD (P < 0.001). In the reverse MR analysis, total NMOSD was found to decrease the level of BAT (P < 0.001) and increase the level of SHBG (P = 0.001) in females.
conclusionFindings of this MR analysis revealed mutual causal associations between sex hormones and NMOSD, which provided novel perspectives about the gender-related pathogenesis of NMOSD.
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