Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age. The infrequency of SLE in men and disease onset in prepubertal or postmenopausal women suggests a role of estrogen in the predisposition to the disease. Patients with hypergonadotrophic hypogonadism are prone to the development of SLE, and the use of exogenous estrogens in women increases the relative risk of SLE onset and disease flares. These observations provide indirect evidence for an opposite role of estrogens and androgens in the pathogenesis of SLE. We report on a male-to-female transsexual who developed SLE 20 years after sex-reassignment surgery and prolonged estrogen therapy. The role of sex hormones in SLE is revisited.
FrenchMAHughesP. Systemic lupus erythematosus and Klinefelter’s syndrome. Ann Rheum Dis1983; 42: 471–473.
2.
RoubinianJRTalalNGreenspanJSGoodmanJRSiiteriPK. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med1978; 147: 1568–1583.
3.
LucasJAAhmedSACaseyMLMacDonaldPC. Prevention of autoantibody formation and prolonged survival in New Zealand black/New Zealand white F1 mice fed dehydroisoandrosterone. J Clin Invest1985; 75: 2091–2093.
4.
VerheulHAVerveldMHoefakkerSSchuursAH. Effects of ethinylestradiol on the course of spontaneous autoimmune disease in NZB/W and NOD mice. Immunopharmacol Immunotoxicol1995; 17: 163–180.
5.
RoubinianJRPapoianRTalalN. Androgenic hormones modulate autoantibody responses and improve survival in murine lupus. J Clin Invest1977; 59: 1066–1070.
6.
PetriMOrbaiAMAlarcónGS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum2012; 64: 2677–2686.
7.
GrimaldiCMClearyJDagtasASMoussaiDDiamondB. Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest2002; 109: 1625–1633.
8.
KimWUMinSYHwangSHYooSAKimKJChoCS. Effect of oestrogen on T cell apoptosis in patients with systemic lupus erythematosus. Clin Exp Immunol2010; 161: 453–458.
9.
RiderVJonesSEvansMBassiriHAfsarZAbdouNI. Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. J Rheumatol2001; 28: 2644–2649.
10.
Sánchez-GuerreroJKarlsonEWLiangMHHunterDJSpeizerFEColditzGA. Past use of oral contraceptives and the risk of developing systemic lupus erythematosus. Arthritis Rheum1997; 40: 804–808.
11.
Sánchez-GuerreroJLiangMHKarlsonEWHunterDJColditzGA. Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Ann Intern Med1995; 122: 430–433.
12.
PetriMKimMYKalunianKC. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med2005; 353: 2550–2558.
13.
BuyonJPPetriMAKimMY. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: A randomized trial. Ann Intern Med2005; 142: 953–962.
InserraPZhangZArdestaniSK. Modulation of cytokine production by dehydroepiandrosterone plus melatonin supplementation of old mice. Proc Soc Exp Biol Med1998; 218: 76–82.
16.
KandaNTsuchidaTTamakiK. Testosterone suppresses anti-DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum1997; 40: 1703–1711.
17.
ChangDMChuSJChenHCKuoSYLaiJH. Dehydroepiandrosterone suppresses interleukin 10 synthesis in women with systemic lupus erythematosus. Ann Rheum Dis2004; 63: 1623–1626.
18.
SuzukiTSuzukiNEnglemanEGMizushimaYSakaneT. Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol1995; 99: 251–255.
