Sex Hormones and Prolactin Levels and Their Association with Anti Cardiolipin Antibody in Patients with Systemic Lupus Erythematosus
AbstractPathogenesis of systemic lupus erythematosus (SLE) is complex and multi-factorial. Among various suggested mechanisms for the disease, the hormonal theory has been considered as one of the most important mechanisms. Recently, the association of sex hormones with manifestations of antiphospholipid antibody syndrome (APLS) has been hypothesized. The aim of present study was to assess the serum levels of anticardiolipin antibody (ACA), sex hormones and prolactin in SLE female patients and their association with the disease. This study comprised 40 SLE female patients and 41 healthy age-matched female subjects. For all patients and controls, the serum levels of ACA (IgG and IgM), estradiol, testosterone, progesterone, dehydroepiandrosterone sulfate (DHEA-S) and prolactin were measured by ELISA method. Our study revealed that serum levels of testosterone, DHEA-S and progesterone were significantly lower in SLE patients than control (p<0.001). However, serum levels of estradiol and prolactin were significantly higher in SLE patients compared to controls (p<0.001). There was a significant difference between mild and moderate severity patients group for ACA positivity (95% CI 13.67-41.3; p=0.03). Also, SLE patients with positive ACA showed significantly lower (p<0.001) serum levels of testosterone, DHEA-S and progesterone and significantly higher (p<0.001) estradiol and prolactin serum levels compared to negative ACA patients. The results of our study indicated that expression and metabolism of sex hormones and prolactin are different in female SLE patients compared to healthy subjects. It seems, change in serum levels of these hormones is related to higher SLE disease activity, increased thrombotic risks and increased renal involvement.
1. Hochberg M. Epidemiology of systemic lupus erythematosus. In:Lahita RG, editor. Systemic lupus erythematosus.2nd Ed. NewYork: Churchill Livingstone; 1992:103–17.2. Petri M. Epidemiology of systemic lupus erythematosus. Best Pract Res ClinRheumatol 2002; 16(5):847–58.3. Whitacre CC, Reingold SC, O’Looney PA. A gender gap in autoimmunity. Science 1999; 283(5406):1277–8.4. Schwartzman-Morris J, Putterman C. Gender differences in the pathogenesis and outcome of lupus and of lupus nephritis. Clin Dev Immunol 2012; 2012:604892.5. Wizemann TM, Pardue ML, editors. Exploring the biological contributions to human health: does sex matter? Committee on Understanding the Biology of Sex and Gender Differences, Institute of Medicine. Washington DC: National Academies Press; 2001:13–27, 117–72, 233–8.6. Lahita RG. Sex hormones and systemic lupus erythematosus. Rheum Dis Clin North Am 2000; 26(4):951–68.7. McMurray RW. Sex hormones in the pathogenesis of systemic lupus erythematosus. Front Biosci 2001; 6:193–206.8. Walker SE, Jacobson JD. Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases. Rheum Dis Clin North Am 2000; 26(4):713–36.9. Medeiros PB, Febroˆnio M V, Bonfa´ E, Borba EF, Takiuti AD, et al. Menstrual and hormonal alterations in juvenile systemic lupus erythematosus. Lupus 2009; 18(1):38–43.10. Verthelyi D. Sex hormones as immunomodulators in health and disease. IntImmunopharmacol 2001; 1(6):983-93.11. Lee YC. Synergistic Effect of Various Regulatory Factors in Th1/Th2 Balance; Immunotherapeutic Approaches in Asthma. Int J Biomed Sci2008; 4(1):8–13.12. Ackerman LS. Sex hormones and the genesis of autoimmunity. Arch Dermatol. 2006; 142: 371–376.13. Holroyd CR, Edwards CJ. The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus. Climacteric 2009; 12(5):378-86.14. Gompel A, Piette JC. Systemic lupus erythematosus and hormone replacement therapy. Menopause Int. 2007; 13(2):65–70.15. Cojocru M, Cojocaru IM, Silosi I. Some Neuro-immuno-endocrine aspects In Autoimmune Diseases. Medica a J of clin Med 2008; 3(1):35-9.16. Jiang B, Sun L, Hao S, Li X, Xu Y, Hou Y. Estrogen modulates bone marrow-derived DCs in SLE murine model-(NZB x NZW) F1 female mice. Immunol Invest 2008; 37(3):227–43.17.Medeiros PB,Febrônio MV,Bonfá E,Borba EF,TakiutiAD,Silva CA. Menstrual and hormonal alterations in juvenile systemic lupus erythematosus. Lupus 2009 18(1):38–43.18. Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Seriolo B, et al. Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 2004; 13(9):635-8.19. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003; 38(1):13-22.20. Seli E, AriciA. Sex steroid and the immune system. immunol, Allergy Clin North Am 2002; 22(3):407-33.21. Zandman-Goddard G, Peeva E, Shoenfeld Y. Gender and autoimmunity. Autoimmun Rev 2007; 6(6):366-72.22. Rood MJ, Van Der Velde EA, Ten Cate R, Breedveld FC, Huizinga TW. Female sex hormones at the onset of systemic lupus erythematosus affect survival. Br J Rheumatol 1998; 37(9):1008-10.23. Cravioto MD,Durand-Carbajal M,Jiménez-Santana L,Lara-Reyes P,Seuc AH,Sánchez-Guerrero J.et al. Efficacy of estrogen plus progestin on menopausal symptoms in women with systemic lupus erythematosus: a randomized, double-blind, controlled trial. Arthritis Care Res (Hoboken)2011; 63(12):1654–63.24. Uthman I, Salti I, Khamashta M. Endocrinologic manifestations of the antiphospholipd syndrome. Lupus 2006; 15(8):485-9.25. de Carvalho JF. Influence of gender on the clinical and laboratory spectra of patients with primary antiphospholipid syndrome. RheumatolInt 2010; 31(5):647-50.26. Lim W, Crowther MA. Antiphospholipid antibodies: a critical review of the literature. CurrOpinHematol 2007; 14(5):494-9.27. McIntyre JA, Wagenknecht, DR, Faulk WP. Antiphospholipid antibodies: discovery, definitions, detection and disease. Progr Lipid Res 2003; 42(3):176-237.28. Tiskievicz F, Mallmann ES, Brenol JC, Xavier RM, Spritzer PM. Prolactin, estradiol and anticardiolipin antibodies in premenopausal women with systemic lupus erythematosus: a pilot study. Rev Bras Reumatol 2011;51(5):460-4.29. Cravioto M-D-C, Durand-Carbajal M, Jime´nez-Santana L, Lara-Reyes P, Seuc AH, Sánchez-Guerrero J.. Efficacy of estrogen plus progestin on menopausal symptoms in women with systemic lupus erythematosus: a randomized, double-blind, controlled trial. Arthritis Care Res (Hoboken) 2011; 63(12):1654–63.30. Moser KL, Kelly JA, Lessard CJ, Harley JB. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun 2009; 10(5):373-9.31. Wilson JD, Foster DW. Williams’s textbook of endocrinology. 8th ed. Philadelphia: WB Saunders; 1992.32. McMurray RW, May W. Sex hormones and systemic lupus erythematosus: review and meta-analysis. Arthritis Rheum 2003; 48(8):2100-10.33. Vennemann F, Tholen S. Sex hormones in lupus erythematosus. Z Hautkr. 1986; 61:791–9.34. Jungers P, Nahoul K, Pelissier C, Dougados M, Athea N, Tron F, et al. A study of plasma androgen levels in women with systemic lupus erythematosus. Presse Med 1983; 12(11):685–8.35. Feher KG, Bencze G, Ujfalussy J, Feher T. Serum steroid hormone levels in systemic lupus erythematosus (SLE). Acta Med Hung 1987; 44(4):321–7.36. Lahita RG, Bradlow HL, Ginzler E, Pang S, New M. Low plasma androgens in women with systemic lupus erythematosus. Arthritis Rheum1987; 30(3):241–8.37. Arnalich F, Benito-Urbina S, Gonzalez-Gancedo P, Iglesias E, de Miguel E, Gijon-Banos J. Inadequate production of progesterone in women with systemic lupus erythematosus. Br J Rheumatol 1992; 31(4):247–51.38. Folomeev M, Dougados M, Beaune J, Kouyoumdjian JC, Nahoul K, Amor B, et al. Plasma sex hormones and aromatase activity in tissues of patients with systemic lupus erythematosus. Lupus 1992; 1(3):191–5.39. Cheng W, Li LS. Blood levels of sex hormone in lupus nephritis and their relationship to lupus activity. Chin Med J (Engl) 1993; 106(1):49–52.40. Munoz JA, Gil A, Lopez-Dupla JM, Vazquez JJ, Gonzalez-Gancedo P. Sex hormones in chronic systemic lupus erythematosus: correlation with clinical and biological parameters. Ann Med Interne (Paris) 1994; 145(7):459–63.41. Verthelyi D, Petri M, Ylamus M, Klinman DM. Disassociation of sex hormone levels and cytokine production in SLE patients. Lupus 2001; 10(5):352–8.42. Mackworth-Young CG, Parke AL, Morley KD, Fotherby K, Hughes GR. Sex hormones in male patients with systemic lupus erythematosus: a comparison with other disease groups. Eur J RheumatolInflamm 1983; 6(3):228–32.43. Miller MH, Urowitz MB, Gladman DD, Killinger DW. Systemic lupus erythematosus in males. Medicine (Baltimore) 1983; 62(5):327–34.44. Carrabba M, Giovine C, Chevallard M, Angelini M, Ambrosi B, Travaglini P. Abnormalities of sex hormones in men with systemic lupus erythematosus. ClinRheumatol 1985; 4(4):420–5.45. Lavalle C, Loyo E, Paniagua R, Bermudez JA, Herrera J, Graef A, et al. Correlation study between prolactin and androgens in male patients with systemic lupus erythematosus. J Rheumatol 1987; 14(2):268–72.46. Sequeira JF, Keser G, Greenstein B, Wheeler MJ, Duarte PC, Khamashta MA, et al. Systemic lupus erythematosus: sex hor-mones in male patients. Lupus 1993; 2(5):315–7.47. Chang DM, Chang CC, Kuo SY, Chu SJ, Chang ML. Hormonal profiles and immunological studies of male lupus in Taiwan. ClinRheumatol 1999; 18(2):158–62.48. Vilarinho ST, Costallat LT. Evaluation of the hypothalamic-pituitary-gonadal axis in males with systemic lupus erythematosus. J Rheumatol 1998; 25(6):1097–103.49. Mok CC, Lau CS. Profile of sex hormones in male patients with systemic lupus erythematosus. Lupus 2000; 9(4):252–7.50. Inman RD, Jovanovic L, Markenson JA, Longcope C, Dawood MY, Lockshin MD. Systemic lupus erythematosus in men: genetic and endocrine features. Arch Intern Med 1982; 142(10):1813–5.51. Inman RD. Systemic lupus erythematosus in the male: a genetic and endocrine study [abstract]. Arthritis Rheum 1979; 22:624.52. Karanth S, McCann SM. Interior pituitary hormone control by interleukin 2.Proc NatlAcadSci U S A. 1991; 88(7):2961-5.53. Lahita RG, Bradlow HL, Fishman J, Kunkel HG. Abnormal estrogen and androgen metabolism in the human with systemic lupus erythematosus. Am J Kidney Dis 1982; 2(1 Suppl 1):206–11.54. Lahita RG, Cheng CY, Monder C, Bardin CW. Experience with 19-nortestosterone in the therapy of systemic lupus erythematosus: worsened disease after treatment with 19-nortestosterone in men and lack of improvement in women. J Rheumatol 1992; 19(4):547-55.55. Lahita RG, Bradlow HL, Kunkel HG, Fishman J. Alterations of estrogen metabolism in SLE. Arthritis Rheum 1979; 22(11):1195–2001.56. Lahita RG, Kunkel HG, BradlowHL.Increased oxidation of testosterone in systemic lupus erythematosus.Arthritis Rheum 1983; 26(12):1517–21.57. Spangelo BL, Judd AN, Isakson PC, MacLeod RN. Interleukin-6 stimulates anterior pituitary hormone release in vitro. Endocrinol 1989; 125(1):575–7.58. Yamaguchi M, Koike K, Matsuzaki N, Yoshimoto Y, Taniguchi T, Miyake A, et al. The interferon family stimulates the secretion of prolactin and interleukin-6 by the pituitary gland in vitro. J Endocrinol Invest 1991; 14(6):457–61.59. Karanth S, McCann SM. Anterior pituitary hormone control by interleukin-2. Proc Natl AcadSci USA 1991; 88(7):2961–5.60. Elbourne KB, Keisler D, McMurray RW. Differential effects of estrogen and prolactin on autoimmune disease in the NZB/NZW F1 mouse model of systemic lupus erythematosus. Lupus 1998; 7(6):420–7.61. Jara-Quezada L, Graef A, Lavalle C. Prolactin and gonadal hormones during pregnancy in systemic lupus erythematosus. J Rheumatol 1991; 18(3):349–53.62. Doria A, Cutolo M, Ghirardello A, Zampieri S, Vescovi F, Sulli A, et al. Steroid hormones and disease activity during pregnancy in systemic lupus erythematosus. Arthritis Rheum (Arthritis Care Res) 2002; 47(2):202–9.63. Lahita RG, Cheng CY, Monder C, Bardin CW. Experience with 19-nortestosterone in the therapy of systemic lupus erythematosus: worsened disease after treatment with 19-nortestosterone in men and lack of improvement in women. J Rheumatol 1992; 19(4):547–55.64. Sturgess AD, Evans DT, Mackay IR, Riglar A. Effects of the oestrogen antagonist tamoxifen on disease indices in systemic lupus erythematosus. J Clin Lab Immunol 1984; 13(1):11–4.65. Olsen NJ, Kovacs WJ. Gonadal steroids and immunity.Endocr Rev 1996; 17(4):369-84.66. Rastin M, Hatef MR, Tabasi N, Sheikh A, MoradAbbasi J, Mahmoudi M. Sex hormones and peripheral white blood cell subsets in systemic lupus erythematosus patients.Iran J Immunol 2007; 4(2):110-5.67. Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46(11):2924–7.68. Van Vollenhoven RF, Engleman DG, McGuire JL. Dehydroepi-androsterone in systemic lupus erythematosus: results of a double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheum 1995; 38:1826–31.69. Barry NN, McGuire JL, van Vollenhoven RF. Dehydroepiandro-sterone in systemic lupus erythematosus: relationship between dosage, serum levels, and clinical response. J Rheumatol 1998; 25(12):2352–6.70. Van Vollenhoven RF, Morabito LM, Engleman EG, McGuire JL. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol 1998; 25(2):285–9.71. Abul-Saoud AM, Al-Shourbagy EA, Bdullah SH. ImpactofAnticardiolipin Antibodiesand HyperprolactinemiaonLabratoary, Immunologicaland Histopathologicalparametersof LUPUS NEPHRITIS.72. Lahita RG. DHEA and lupus. Paper presented at: Sixth International Lupus Conference; March 24-28, 2001; Barcelona, Spain.73. Pando JA, Gourley MF, Wilder RL, Crofford LJ. Hormonal supplementation as treatment for cyclical rashes in patients with systemic lupus erythematosus. JRheumatol 1995; 22(1):2159–62.74. Mok CC, Lau CS, Tam SCF. Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients. Br J Rheumatol 1997; 36(9):986–9.75. Batuca JR, Amaral MC, Alves JD. Humoral mechanisms of atherogenesis. Ann N Y Acad Sci. 2009; 1173:401-8.