Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Postmenopausal Hormone, Hematology and Immune Modulation in Rheumatoid Arthritis Patients

Luma Qasim Ali 1, Firas Salih Abdulhadi 1, Ban Talib El-Haboby 1, Jamela Jouda 1*

+ Author Affiliations

Journal of Angiotherapy 8(3) 1-9 https://doi.org/10.25163/angiotherapy.839587

Submitted: 10 January 2024  Revised: 05 March 2024  Published: 08 March 2024 

Abstract

Background: There is a significant hormonal shift in Postmenopausal women with low levels of estrogen and progesterone. These changes may cause the pathogenesis of autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), which exhibit a higher prevalence in women. It is crucial to determine the pathophysiology and treatment strategies and to understand the hematological, hormonal, and immunological differences in postmenopausal women with RA and SLE. This study determined the hematological, hormonal, and immunological parameters in postmenopausal RA and SLE patients. Methods: 75 postmenopausal women (aged 52-65 years) were recruited in this study, comprising 25 with RA, 25 with SLE, and 25 with healthy controls. Blood samples were collected for complete blood count (CBC), erythrocyte sedimentation rate (ESR), and serum hormone and immunoglobulin assays. Statistical analyses were conducted using Fisher's test, t-test, and ANOVA, with significance at p < 0.05. Results: In postmenopausal RA and SLE patients, significant blood parameter differences were observed versus controls. RA showed elevated WBC count (18.189±0.782) and PLT (373.778±14.644), lower RBC (4.009±0.149) and Hb (11.705±0.328). SLE had lower WBC (3.016±0.595), RBC (4.293±0.112), and Hb (12.270±0.312), and higher RDW (18.830±1.719) and lower MPV (8.327±0.314). Hormonal differences included higher FSH and lower LH, estrogen, and testosterone in both groups, while RA exhibited decreased cortisol and increased progesterone, and both diseases showed elevated rheumatoid factor (RF), ESR, and immunoglobulin E (IgE). Conclusion: Postmenopausal women with RA and SLE showed distinct hematological, hormonal, and immunological profiles compared to healthy controls. This study demonstrated the complex interplay between hormonal changes and autoimmune diseases, warranting further investigation into their underlying mechanisms and potential implications for treatment strategies.

Keywords: CBC, Cortisol, IgE, Postmenopausal, Rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE), Hormonal changes, Hematological parameters

References

Allanore, Y., Hilliquin, P., Coste, J., Renoux, M., & Menkes, C. J. (1998). Decreased prevalence of atopy in rheumatoid arthritis. The Lancet, 351(9101), 497.

https://doi.org/10.1016/S0140-6736(05)78684-0

 

Baker, J. F., & Ghio, A. J. (2009). Iron homoeostasis in rheumatic disease. Rheumatology, 48(11), 1339-1344

https://doi.org/10.1093/rheumatology/kep221

 

Bartholomew, J. S., Evanson, J. M., & Woolley, D. E. (1991). Serum IgE anti-cartilage collagen antibodies in rheumatoid patients. Rheumatology international, 11, 37-40.

https://doi.org/10.1007/BF00290249

 

Bodis, J., Koppan, M., Garai, J., Zambo, K., & Torok, A. (2003). Issues to debate on the Women's Health Initiative: Estrogen: an instrument or the conductor of the orchestra?. Human Reproduction, 18(8), 1561-1563

https://doi.org/10.1093/humrep/deg328

 

Camussi, G., Tetta, C., & Benveniste, J. (1982). Detection of basophil sensitization by IgE antibodies to nuclear antigens in connective tissue diseases. International Archives of Allergy and Immunology, 69(4), 358-362.

https://doi.org/10.1159/000233200

 

Chandrashekara, S., Rajendran, A., Jaganath, A. B., & Krishnamurthy, R. (2015). Neutrophil-lymphocyte ratio, pain perception, and disease activity score may serve as important predictive markers for sustained remission in rheumatoid arthritis. Reumatismo, 67(3), 109-115.

https://doi.org/10.4081/reumatismo.2015.838

 

Chover-Gonzalez, A. J., Jessop, D. S., Tejedor-Real, P., Gibert-Rahola, J., & Harbuz, M. S. (2000). Onset and severity of inflammation in rats exposed to the learned helplessness paradigm. Rheumatology, 39(7), 764-771.

https://doi.org/10.1093/rheumatology/39.7.764

 

Cross, M., Smith, E., Hoy, D., Carmona, L., Wolfe, F., Vos, T., ... & March, L. (2014). The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Annals of the rheumatic diseases, 73(7), 1316-1322.‏.‏

https://doi.org/10.1136/annrheumdis-2013-204627

 

Dos Santos, B. P., Valverde, J. V., Rohr, P., Monticielo, O. A., Brenol, J. C. T., Xavier, R. M., & Chies, J. A. B. (2012). TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil. Lupus, 21(3), 302-309.

https://doi.org/10.1177/0961203311425522

 

Durán-Barragán, S., Bátiz-Andrade, J. P., Valenzuela-Marrufo, R., & Alarcón, G. S. (2021). Influence of the environment, gender, and hormones on systemic lupus erythematosus: A narrative review. Revista Colombiana de Reumatología, 28, 177-190.

https://doi.org/10.1016/j.rcreu.2021.02.008

 

EG, B. (1996). White blood cell counts in persons aged 65 years or more from the cardiovascular health study. Am J Epidemiol, 143, 1107-1115

https://doi.org/10.1093/oxfordjournals.aje.a008687

 

Ganz, T. (2019). Anemia of inflammation. New England Journal of Medicine, 381(12), 1148-1157.

https://doi.org/10.1056/NEJMra1804281

 

Gilliver, S. C. (2010). Sex steroids as inflammatory regulators. The Journal of steroid biochemistry and molecular biology, 120(2-3), 105-115.

https://doi.org/10.1016/j.jsbmb.2009.12.015

 

Goemaere, S., Ackerman, C., Goethals, K., De Keyser, F., Van Der Straeten, C., Verbruggen, G., ... & Veys, E. M. (1991). Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition: J. Rheumatol. 1990 17/12 (1620-1622). Maturitas, 13(4), 340-341.

https://doi.org/10.1016/0378-5122(91)90251-K

 

González Naranjo, L. A. (2008). Mofetil micofenolato como tratamiento de las manifestaciones no renales del lupus eritematoso sistémico. Revista Colombiana de Reumatología, 15(4), 307-320.

 

Grennan, D. M., & Palmer, D. G. (1979). Serum IgE concentrations in rheumatoid arthritis: lack of correlation with gold toxicity. British Medical Journal, 2(6203), 1477.

https://doi.org/10.1136/bmj.2.6203.1477

 Ghufran Abd Omran Abdulridha, Mustafa Abdulkadhim Hussein, Suhad Rasheed Majeed. (2024). High Growth Differentiation Factor-15 (GDF-15) in Rheumatoid Arthritis Patients Potential Risk for Cardiovascular Disease, Journal of Angiotherapy, 8(3), 1-8, 9595

Gutierrez, M. A., Garcia, M. E., Rodriguez, J. A., Rivero, S., & Jacobelli, S. (1998). Hypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus. Lupus, 7(6), 404-408.

https://doi.org/10.1191/096120398678920343

 

Hall, G. M., Larbre, J. P., Spector, T. D., Perry, L. A., & Da Silva, J. A. P. (1996). A randomized trial of testosterone therapy in males with rheumatoid arthritis. Rheumatology, 35(6), 568-573.

https://doi.org/10.1093/rheumatology/35.6.568

 

Harbuz, M. S., CHOVER-GONZALEZ, A. J., & Jessop, D. S. (2003). Hypothalamo-pituitary-adrenal axis and chronic immune activation. Annals of the New York Academy of Sciences, 992(1), 99-106.

https://doi.org/10.1111/j.1749-6632.2003.tb03141.x

 

Hassan, W. U., Keaney, N. P., Holland, C. A., & Kelly, C. A. (1994). Bronchial reactivity and airflow obstruction in rheumatoid arthritis. Annals of the rheumatic diseases, 53(8), 511-514.

https://doi.org/10.1136/ard.53.8.511

 

Hunder, G. G., & Gleich, G. J. (1974). Immunoglobulin E (IgE) levels in serum and synovial fluid in rheumatoid arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 17(6), 955-963.

https://doi.org/10.1002/art.1780170606

 

Imrich, R., Vigas, M., Rovensky, J., Aldag, J. C., & Masi, A. T. (2009). Adrenal plasma steroid relations in glucocorticoid-naïve premenopausal rheumatoid arthritis patients during insulin-induced hypoglycemia test compared to matched normal control females. Endocrine regulations, 43(2), 65-73.

 

Isik, M., Sahin, H., & Hüseyin, E. (2014). New platelet indices as inflammatory parameters for patients with rheumatoid arthritis. European journal of rheumatology, 1(4), 144.

https://doi.org/10.5152/eurjrheumatol.2014.140023

 

Katsuyama, T., Sada, K. E., & Makino, H. (2014). Current concept and epidemiology of systemic vasculitides. Allergology International, 63(4), 505-513.

https://doi.org/10.2332/allergolint.14-RAI-0778

 

Kounis, N. G., Soufras, G. D., Tsigkas, G., & Hahalis, G. (2015). White blood cell counts, leukocyte ratios, and eosinophils as inflammatory markers in patients with coronary artery disease. Clinical and Applied Thrombosis/Hemostasis, 21(2), 139-143.

https://doi.org/10.1177/1076029614531449

 

Kulkarni, M., & Hiremath, S. (2019). Hematological changes in postmenopausal women. National Journal of Physiology, Pharmacy and Pharmacology, 9(3), 248-248.Obeagu EI, Obeagu GU. A review on haematological profile in menstruating, premenopausal and menopausal women. IJARBS.2016; 3(11), 92-108.

https://doi.org/10.5455/njppp.2019.9.0101515012019

 

Lechner, O., Dietrich, H., dos Santos, A. O., Wiegers, G. J., Schwarz, S., Harbutz, M., ... & Wick, G. (2000). Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fasIpr mice. Journal of Autoimmunity, 14(4), 325-333.

https://doi.org/10.1006/jaut.2000.0375

 

Lee, C., Almagor, O., Dunlop, D. D., Manzi, S., Spies, S., Chadha, A. B., & Ramsey-Goldman, R. (2006). Disease damage and low bone mineral density: an analysis of women with systemic lupus erythematosus ever and never receiving corticosteroids. Rheumatology, 45(1), 53-60.

https://doi.org/10.1093/rheumatology/kei079

 

Martinez-Banos, D., Crispín, J. C., Lazo-Langner, A., & Sánchez-Guerrero, J. (2006). Moderate and severe neutropenia in patients with systemic lupus erythematosus. Rheumatology, 45(8), 994-998

https://doi.org/10.1093/rheumatology/kel016

 

Mei, Q., Mundinger, T. O., Lernmark, A., & Taborsky Jr, G. J. (2002). Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats. Diabetes, 51(10), 2997-3002.

https://doi.org/10.2337/diabetes.51.10.2997

 

Miller, L. E., Jüsten, H. P., Schcölmerich, J., & Straub, R. H. (2000). The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages. The FASEB Journal, 14(13), 2097-2107.‏.‏

https://doi.org/10.1096/fj.99-1082com

 

Milman, N., Kirchhoff, M., & Jørgensen, T. (1992). Iron status markers, serum ferritin and hemoglobin in 1359 Danish women in relation to menstruation, hormonal contraception, parity, and postmenopausal hormone treatment. Annals of hematology, 65, 96-102

https://doi.org/10.1007/BF01698138

 

Mirand, E. A., & Gordon, A. S. (1966). Mechanism of estrogen action in erythropoiesis. Endocrinology, 78(2), 325-332.

https://doi.org/10.1210/endo-78-2-325

 

Mirzayan, M. J., Schmidt, R. E., & Witte, T. (2000). Prognostic parameters for flare in systemic lupus erythematosus. Rheumatology, 39(12), 1316-1319

https://doi.org/10.1093/rheumatology/39.12.1316

 

Mizushima, Y., Shoji, Y., Hoshi, K., & Kiyokawa, S. (1984). Detection and clinical significance of IgE rheumatoid factor. The Journal of Rheumatology, 11(1), 22-26.

 

Mok, C. C., & Lau, C. S. (2000). Profile of sex hormones in male patients with systemic lupus erythematosus. Lupus, 9(4), 252-257.

https://doi.org/10.1191/096120300680198926

 

O'DRISCOLL, B. R. C., Milburn, H. J., Kemeny, D. M., Cochrane, G. M., & Panayi, G. S. (1985). Atopy and rheumatoid arthritis. Clinical & Experimental Allergy, 15(6), 547-553.

https://doi.org/10.1111/j.1365-2222.1985.tb02308.x

 

Park, E. H., Kang, E. H., Lee, Y. J., & Ha, Y. J. (2023). Impact of early age at menopause on disease outcomes in postmenopausal women with rheumatoid arthritis: a large observational cohort study of Korean patients with rheumatoid arthritis. RMD open, 9(1), e002722.

https://doi.org/10.1136/rmdopen-2022-002722

 

Parks, C. G., Biagini, R. E., Cooper, G. S., Gilkeson, G. S., & Dooley, M. A. (2010). Total serum IgE levels in systemic lupus erythematosus and associations with childhood onset allergies. Lupus, 19(14), 1614-1622.

https://doi.org/10.1177/0961203310379870

 

Pistiner, M., Wallace, D. J., Nessim, S., Metzger, A. L., & Klinenberg, J. R. (1991, August). Lupus erythematosus in the 1980s: a survey of 570 patients. In Seminars in arthritis and rheumatism (Vol. 21, No. 1, pp. 55-64). WB Saunders.

https://doi.org/10.1016/0049-0172(91)90057-7

 

Pizzorno, J. E., & Murray, M. T. (2020). Textbook of Natural Medicine-E-Book: Textbook of Natural Medicine-E-Book. Elsevier Health Sciences.

 

Raine, C., & Giles, I. (2022). What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis?. Frontiers in Medicine, 9, 909879.

https://doi.org/10.3389/fmed.2022.909879

 

Rey, A., Kabiersch, A., Petzoldt, S., & Besedovsky, H. O. (2003). Sympathetic abnormalities during autoimmune processes. Annals of the New York Academy of Sciences, 992(1), 158-167.

https://doi.org/10.1111/j.1749-6632.2003.tb03146.x

 

Schedlowski, M., Hosch, W., Oberbeck, R., Benschop, R. J., Jacobs, R., Raab, H. R., & Schmidt, R. E. (1996). Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. Journal of immunology (Baltimore, Md.: 1950), 156(1), 93-99.

https://doi.org/10.4049/jimmunol.156.1.93

 

Shrivastava, A. K., Singh, H. V., Raizada, A., Singh, S. K., Pandey, A., Singh, N., ... & Sharma, H. (2015). Inflammatory markers in patients with rheumatoid arthritis. Allergologia et immunopathologia, 43(1), 81-87.

https://doi.org/10.1016/j.aller.2013.11.003

 

Silverman, M. N., & Sternberg, E. M. (2012). Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Annals of the new York Academy of Sciences, 1261(1), 55-63.

https://doi.org/10.1111/j.1749-6632.2012.06633.x

 

Starkebaum, G., Price, T. H., Lee, M. Y., & Arend, W. P. (1978). Autoimmune neutropenia in systemic lupus erythematosus. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 21(5), 504-512.

https://doi.org/10.1002/art.1780210503

 

Stokes, K. Y., & Granger, D. N. (2012). Platelets: a critical link between inflammation and microvascular dysfunction. The Journal of physiology, 590(5), 1023-1034

https://doi.org/10.1113/jphysiol.2011.225417

 

Straub, R. H., Günzler, C., Miller, L. E., Cutolo, M., Schölmerich, J., & Schill, S. (2002). Anti-inflammatory cooperativity of corticosteroids and norepinephrine in rheumatoid arthritis synovial tissue in vivo and in vitro. The FASEB journal, 16(9), 993-1000.

https://doi.org/10.1096/fj.02-0085com

Subasini Uthirapathy. (2023). Effect of Plumbago zeylanica on Analgesia and Arthritis, Journal of Angiotherapy, 7(1), 1-7, 9370

Talsania, M., & Scofield, R. H. (2017). Menopause and rheumatic disease. Rheumatic Disease Clinics, 43(2), 287-302.

https://doi.org/10.1016/j.rdc.2016.12.011

 

Talukdar, M., Barui, G., Adhikari, A., Karmakar, R., Ghosh, U. C., & Das, T. K. (2017). A study on association between common haematological parameters and disease activity in rheumatoid arthritis. Journal of clinical and diagnostic research: JCDR, 11(1), EC01

https://doi.org/10.7860/JCDR/2017/23524.9130

 

Tekeoglu, I., Gürol, G., Harman, H., Karakeçe, E., & Çiftçi, I. H. (2016). Overlooked hematological markers of disease activity in rheumatoid arthritis. International journal of rheumatic diseases, 19(11), 1078-1082.

https://doi.org/10.1111/1756-185X.12805

 

Tengstrand, B., Carlström, K., & Hafström, I. (2009). Gonadal hormones in men with rheumatoid arthritis-from onset through 2 years. The Journal of rheumatology, 36(5), 887-892.

https://doi.org/10.3899/jrheum.080558

 

Verga Falzacappa, M. V., Vujic Spasic, M., Kessler, R., Stolte, J., Hentze, M. W., & Muckenthaler, M. U. (2007). STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood, 109(1), 353-358

https://doi.org/10.1182/blood-2006-07-033969

 

Verthelyi, D., Petri, M., Ylamus, M., & Klinman, D. M. (2001). Disassociation of sex hormone levels and cytokine production in SLE patients. Lupus, 10(5), 352-358.‏.‏

https://doi.org/10.1191/096120301674365881

 

Voulgarelis, M., Giannouli, S., Tasidou, A., Anagnostou, D., Ziakas, P. D., & Tzioufas, A. G. (2006). Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: a clinicopathological study. American journal of hematology, 81(8), 590-597.

https://doi.org/10.1002/ajh.20593

 

Voulgarelis, M., Kokori, S. I., Ioannidis, J. P., Tzioufas, A. G., Kyriaki, D., & Moutsopoulos, H. M. (2000). Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin. Annals of the rheumatic diseases, 59(3), 217-222.

https://doi.org/10.1136/ard.59.3.217

 

Wanitpongpun, C., Teawtrakul, N., Mahakkanukrauh, A., Siritunyaporn, S., Sirijerachai, C., & Chansung, K. (2012). Bone marrow abnormalities in systemic lupus erythematosus with peripheral cytopenia. Clin Exp Rheumatol, 30(6), 825

 

Yousif, N. H., & Ibraheem, S. R. (2020). Comparison of Some Physiological Parameters in Female Rheumatoid Arthritis Patients in Pre-and Postmenopausal Stages. Iraqi Journal of Science, 1926-1931.

https://doi.org/10.24996/ijs.2020.61.8.9

 

Yousif, N. H., & Ibraheem, S. R. (2020). Comparison of Some Physiological Parameters in Female Rheumatoid Arthritis Patients in Pre-and Postmenopausal Stages. Iraqi Journal of Science, 1926-1931.

https://doi.org/10.24996/ijs.2020.61.8.9

 

Zhang, X., Qiao, P., Pan, J., & Wu, F. (2022). High follicle-stimulating hormone level associated with risk of rheumatoid arthritis and disease activity. Frontiers in Endocrinology, 13, 862849.

https://doi.org/10.3389/fendo.2022.862849

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