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Table 1 Therapeutic effects of estrogen and DHT and their derivatives in various autoimmune disease conditions

From: Mechanisms of sex hormones in autoimmunity: focus on EAE

Disease Estrogen/its derivatives DHT/its derivatives
Humans Animal models Humans Animal models
Multiple sclerosis Reduced Th1 response and TNF-α levels with a shift towards Th2 (IL-5, and IL-10) and reduction in lesions in the brain and relapse rate [122, 123, 168] Enhanced B-reg and T-regs, higher serum IgG1 levels, reduced Th1, Th17 response with a shift towards Th2, as evidenced by increased IL-5 (males) and IL-10 levels, with decreased IFN-γ, TNF-α, IL-2, IL-6, IL-17, and IL-23 levels [130, 131, 169, 170] Reduced DTH response, increased NK cells, increased TGF-β1 and decreased IL-2 levels, decreased fatigue, increased gray matter volume and decreased CD4+ T cell infiltrates [124, 125, 135] Significant decrease in EAE severity, with skewness of Th1/Th17:T-reg ratio towards T-reg, and a shift towards Th2 response (increased IL-10) and decreased IFN-γ level [132, 135, 165,165,166,167]
Rheumatoid arthritis Patients with high serum E2 showed reductions in VPS, AI [171] Significant reduction in alkaline phosphatase, TNF-α, IL-1β, IL-6 and anti-type-II collagen autoantibody levels, and reduced disease severity [172,173,174] Improved clinical signs with increased serum testosterone levels and CD8+ T cells, with decreased CD4+:CD8+ ratio, reduction in tender joints [175, 176] Decreased autoantibody generation and joint inflammation, reduction in TNF-α and PGE-2 with reduced inflammatory infiltrates [73, 177, 178]
Systemic lupus erythematosus No significant benefits were noted No significant benefits were noted Reduced disease severity, restoration of normal serum testosterone levels with reduced hematologic and serologic abnormalities [179,180,181] Reduced disease severity with increased survival rate with no autoantibody formation [182]
Sjögren’s syndrome No significant benefits were noted No significant benefits were noted, but has been shown to offer some level of protection against Sjögren’s syndrome-like disease Reduced ESR rates, increased testosterone levels offering disease protection, reduced dry-eyes and dry-mouth symptoms [183, 184] Reduced lymphocyte infiltrations and reversal of autoimmune sequeale in lacrimal gland [185,186,187]
Hashimoto’s thyroiditis Not tested Not tested Inverse correlation between testosterone and thyroid autoimmunity, improved thyroid secretory function [188] Reduced disease incidence and pathology, and drastic reduction in thyroglobulin autoantibodies [189]
Crohn’s disease Not tested Not tested Improved CDAI with reduced serum CRP, increased hemoglobin level, and reduced inflammation [190, 191] Not tested
Psoriasis Not tested Not tested Normal serum testosterone levels, improved disease score, reduced CRP and improved obesity [192] Not tested
Type-I diabetes Not tested Not tested Improved glycemic control with reduced fasting glucose and HbA1c [193] Not tested
Graves’ disease Not tested Not tested Not tested Amelioration of disease severity with a shift from Th1 to Th2 response, reduction in IL-2, IFN-γ and increase in IL-4, IL-10, TGF-β, IL-35, and attenuation of thyroid oxidative injuries [194, 195]
Autoimmune cholangitis Not tested Not tested Not tested Decreased pathology with lesser CD4+ liver-infiltrating T cells, reduced expression of CXCL-9, CXCL-10, and IL-17 with increased serum testosterone concentration [196]
Autoimmune orchitis Not tested Not tested Not tested Reduced disease severity, reduction in CD4+ T cells and accumulation of macrophages in testis, with significant increase in T-regs. Substantial decrease in MCP-1, TNF-α, IL-6, IL-2, and IFN-γ [197]
  1. VPS visual analogue pain scale, AI articular index, DTH delayed type hypersensitivity, PGE-2 prostaglandin-E2, ESR erythrocyte sedimentation rate, CDAI Crohn’s disease activity index, CRP c-reactive protein, HbA1c hemoglobin A1c