Beyond the optic disc: Investigating gender-based differences in optic neuritis

Table 1 Ratio female:male in different pathologies

Condition	Female:male ratio	Ref.
Typical MS-related ON	2-3:1	Malik et al[5] and Arnett et al[4]
Multiple sclerosis (overall)	2.73:1 (95 %CI: 2.37-3.09)	Arnett et al[4]
AQP4-NMOSD (overall)	8.89:1	Arnett et al[4]
HIV-positive NMOSD	9-10:1	Borisow et al[6]
HIV-negative NMOSD	≈ 2:1	Borisow et al[6]
MOGAD	≈ 1:1 (some series female > male)	Jurynczyk et al[10] and de Mol et al[14]

MS: Multiple sclerosis; ON: Optic neuritis; AQP4-NMOSD: Aquaporin 4 IgG positive neuromyelitis optica spectrum disorder; NMOSD: Neuromyelitis optica spectrum disorder; MOGAD: Myelin oligodendrocyte glycoprotein antibody disease; HIV: Human immunodeficiency virus.

Table 2 Main hormones and their immunomodulating action

Hormone (life-phase)	Key immunomodulatory actions	Principal experimental/clinical observations
Estradiol/estriol (mid-cycle, pregnancy)	↓ TNF-α, IFN-γ; ↑ IL-10; ER-β activation quiets microglia and CD11c+ cells; promotes oligodendrocyte maturation and remyelination	Third-trimester pregnancy sharply lowers MS/ON relapse rates; women retain more RNFL after ON in high-estrogen states
Progesterone (luteal phase, gestation)	Shifts immunity Th1 → Th2; expands T-regs; suppresses iNOS and Toll-like-receptor signaling; fosters myelin repair	Color-Doppler shows ↑ central-retinal-artery resistance; progesterone analogues ameliorate EAE lesions and enhance remyelination
Testosterone/DHT (male dominance, peri-puberty)	Down-regulates Th1/Th17; induces thymic AIRE; inhibits NF-κB & p38-MAPK in microglia; curtails IL-1β, IL-6, TNF-α; modulates Bax/Bcl-2, caspase-3	Androgen supplementation dampens EAE severity; low testosterone correlates with aggressive MS & greater ON severity in men; DHT shields SH-SY5Y neurons from inflammatory apoptosis
Prolactin (lactation, immune-cell secretion)	Dual role – may boost inflammation yet stimulates oligodendrocyte progenitors	Human data inconclusive; experimental models show both aggravation of EAE and promotion of remyelination

AIRE: Autoimmune regulator; Bax/Bcl-2: Bcl-2–associated X protein / B-cell lymphoma 2; CD11c⁺: Cluster of differentiation 11c–positive immune cells; DHT: Dihydrotestosterone; EAE: Experimental autoimmune encephalomyelitis; ER-β: Estrogen receptor beta; IFN-γ: Interferon gamma; IL: Interleukin; iNOS: Inducible nitric oxide synthase; MAPK: Mitogen-activated protein kinase; MS: Multiple sclerosis; NF-κB: Nuclear factor kappa B; ON: Optic neuritis; RNFL: Retinal nerve fiber layer; SH-SY5Y: Human neuroblastoma cell line SH-SY5Y; Th1/Th2/Th17: T helper cell subsets 1, 2, and 17; TNF-α: Tumor necrosis factor alpha; Tregs: Regulatory T cells.