Половой диморфизм хронических заболеваний – феномен, определяемый различиями гормонального статуса мужчин и женщин.
В этом плане большой интерес представляют эстрогены, обладающие комплексным влиянием на организм. В частности, эстрогены играют важную роль в естественном контроле боли и воспаления. Снижение уровня эстрогенов, связанное с менопаузой или ятрогенным воздействием (гистерэктомия, применение ингибиторов ароматазы), а также мутации генов, отвечающих за синтез структурных компонентов мембранных рецепторов эстрогенов (ESR1 и ESR2), способны существенно снизить позитивные эффекты этих гормонов. Дефицит эстрогенов может стать одной из причин развития серьезных патологических изменений – в частности, формирования хронической боли, связанной с патологией скелетно-мышечной системы.
Sexual dimorphism of chronic diseases is a phenomenon determined by differences in the hormonal status of men and women. In this regard, estrogens, which have a complex effect on the body, are of great interest. In particular, estrogens play an important role in the natural control of pain and inflammation. A decrease in estrogen levels associated with menopause or iatrogenic effects (hysterectomy, use of aromotase inhibitors), as well as mutations of genes responsible for the synthesis of structural components of membrane estrogen receptors (ESR1 and ESR2), can significantly reduce the positive effects of these hormones. Deficiency of estrogen can become one of the reasons for the development of serious pathological changes – in particular, the formation of chronic pain associated with the pathology of the musculoskeletal system.
1. Насонов Е.Л., Яхно Н.Н., Каратеев А.Е., и др. Общие принципы лечения скелетно-мышечной боли: междисциплинарный консенсус. Научно-практическая ревматология. 2016;54(3):247-65 [Nasonov EL, Yakhno NN, Karateev AE, et al. General principles of treatment for musculoskeletal pain: interdisciplinary consensus. Rheumatology Science and Practice. 2016;54(3):247-65 (in Russian)]. DOI:10.14412/1995-4484-2016-247-265
2. Watt FE. Musculoskeletal pain and menopause. Post Reprod Health. 2018;24(1):34-43. DOI:10.1177/2053369118757537
3. Адамян Л.В., Андреева Е.Н., Аполихина И.А., и др. Менопауза и климактерическое состояние у женщины. Клинические рекомендации. М.: Российское общество акушеров-гинекологов, 2021 [Adamian LV, Andreeva EN, Apolikhina IA, et al. Menopauza i klimaktericheskoe sostoianie u zhenshchiny. Klinicheskie rekomendatsii. Moscow: Rossiiskoe obshchestvo akusherov-ginekologov, 2021 (in Russian)].
4. Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol. 2005;105(5 Pt. 1):1063-73. DOI:10.1097/01.AOG.0000158120.47542.18
5. Ho SC, Chan SG, Yip YB, et al. Menopausal symptoms and symptom clustering in Chinese women. Maturitas. 1999;33(3):219-27. DOI:10.1016/s0378-5122(99)00056-0
6. Bardel A, Wallander MA, Wedel H, Svärdsudd K. Age-specific symptom prevalence in women 35-64 years old: a population-based study. BMC Public Health. 2009;9:37. DOI:10.1186/1471-2458-9-37
7. Horimoto Y, Saito M, Kasumi F. Arthralgia in 329 Patients Taking Aromatase Inhibitors. Breast Care (Basel). 2009;4(5):319-23. DOI:10.1159/000236050
8. Sestak I, Cuzick J, Sapunar F, et al. Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol. 2008;9(9):866-72. DOI:10.1016/S1470-2045(08)70182-7
9. Laroche F, Coste J, Medkour T, et al. Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study. J Pain. 2014;15(3):293-303. DOI:10.1016/j.jpain.2013.11.004
10. Borrie AE, Rose FA, Choi YH, et al. Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients. Breast Cancer Res Treat. 2020;183(2):365-72. DOI:10.1007/s10549-020-05777-1
11. Neeck G, Crofford LJ. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 2000;26(4):989-1002.
DOI:10.1016/s0889-857x(05)70180-0; PMID: 11084955
12. Pamuk ON, Dönmez S, Cakir N. Increased frequencies of hysterectomy and early menopause in fibromyalgia patients: a comparative study. Clin Rheumatol. 2009;28(5):561-4. DOI:10.1007/s10067-009-1087-1
13. Vincent A, Whipple MO, Luedtke CA, et al. Pain and other symptom severity in women with fibromyalgia and a previous hysterectomy. J Pain Res. 2011;4:325-9. DOI:10.2147/JPR.S25490
14. Arslan HS, Nursal AF, Inanir A, et al. Influence of ESR1 Variants on Clinical Characteristics and Fibromyalgia Syndrome in Turkish Women. Endocr Metab Immune Disord Drug Targets. 2021;21(7):1326-32. DOI:10.2174/1871530320666200910110915
15. Koca T, Koçyiğit B, Seyithanoğlu M, Berk E. The Importance of G-protein Coupled Estrogen Receptor in Patients With Fibromyalgia. Arch Rheumatol. 2019;34(4):419-25.
DOI:10.5606/ArchRheumatol.2019.7236
16. Smith SB, Reenilä I, Männistö PT, et al. Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain. 2014;155(11):2390-9. DOI:10.1016/j.pain.2014.09.009
17. Malyala A, Kelly MJ, Rønnekleiv OK. Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes. Steroids. 2005;70(5-7):397-406. DOI:10.1016/j.steroids.2005.03.004
18. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J Comp Neurol. 1997;388(4):507-25.
DOI:10.1002/(sici)1096-9861(19971201)388:4<507::aid-cne1>3.0.co;2-6
19. Zhang W, Wu H, Xu Q, et al. Estrogen modulation of pain perception with a novel 17β-estradiol pretreatment regime in ovariectomized rats. Biol Sex Differ. 2020;11(1):2. DOI:10.1186/s13293-019-0271-5
20. Oshima Y, Matsuda K, Yoshida A, et al. Localization of estrogen receptors alpha and beta in the articular surface of the rat femur. Acta Histochem Cytochem. 2007;40(1):27-34. DOI:10.1267/ahc.06015
21. Carlsten H. Immune responses and bone loss: the estrogen connection. Immunol Rev. 2005;208:194-206. DOI:10.1111/j.0105-2896.2005.00326.x
22. Nilsson BO. Modulation of the inflammatory response by estrogens with focus on the endothelium and its interactions with leukocytes. Inflamm Res. 2007;56(7):269-73. DOI:10.1007/s00011-007-6198-z
23. Ushiyama T, Mori K, Inoue K, et al. Association of oestrogen receptor gene polymorphisms with age at onset of rheumatoid arthritis. Ann Rheum Dis. 1999;58(1):7-10. DOI:10.1136/ard.58.1.7
24. Blanton HL, Barnes RC, McHann MC, et al. Sex differences and the endocannabinoid system in pain. Pharmacol Biochem Behav. 2021;202:173107. DOI:10.1016/j.pbb.2021.173107
25. Yan XJ, Feng CC, Liu Q, et al. Vagal afferents mediate antinociception of estrogen in a rat model of visceral pain: the involvement of intestinal mucosal mast cells and 5-hydroxytryptamine 3 signaling. J Pain. 2014;15(2):204-17. DOI:10.1016/j.jpain.2013.10.012
26. Pecins-Thompson M, Brown NA, Kohama SG, Bethea CL. Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus macaques. J Neurosci. 1996;16(21):7021-9. DOI:10.1523/JNEUROSCI.16-21-07021.1996
27. Bethea CL, Lu NZ, Gundlah C, Streicher JM. Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol. 2002;23(1):41-100. DOI:10.1006/frne.2001.0225
28. Martikainen IK, Hirvonen J, Kajander J, et al. Correlation of human cold pressor pain responses with 5-HT(1A) receptor binding in the brain. Brain Res. 2007;1172:21-31. DOI:10.1016/j.brainres.2007.07.036
29. Osikowicz M, Mika J, Przewlocka B. The glutamatergic system as a target for neuropathic pain relief. Exp Physiol. 2013;98(2):372-84. DOI:10.1113/expphysiol.2012.069922
30. Micevych PE, Mermelstein PG. Membrane estrogen receptors acting through metabotropic glutamate receptors: an emerging mechanism of estrogen action in brain. Mol Neurobiol. 2008;38(1):66-77. DOI:10.1007/s12035-008-8034-z
31. Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696-705. DOI:10.1016/j.tins.2003.09.017
32. Yankova M, Hart SA, Woolley CS. Estrogen increases synaptic connectivity between single presynaptic inputs and multiple postsynaptic CA1 pyramidal cells: a serial electron-microscopic study. Proc Natl Acad Sci USA. 2001;98(6):3525-30. DOI:10.1073/pnas.051624598
33. Castrillon EE, Cairns BE, Wang K, et al. Comparison of glutamate-evoked pain between the temporalis and masseter muscles in men and women. Pain. 2012;153(4):823-9. DOI:10.1016/j.pain.2012.01.003
34. Tashiro A, Okamoto K, Bereiter DA. Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons. Neuroscience. 2009;164(4):1813-20. DOI:10.1016/j.neuroscience.2009.09.058
35. Bäckström T, Haage D, Löfgren M, et al. Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons. Neuroscience. 2011;191:46-54. DOI:10.1016/j.neuroscience.2011.03.061
36. Schweizer-Schubert S, Gordon JL, Eisenlohr-Moul TA, et al. Steroid Hormone Sensitivity in Reproductive Mood Disorders: On the Role of the GABAA Receptor Complex and Stress During Hormonal Transitions. Front Med (Lausanne). 2021;7:479646. DOI:10.3389/fmed.2020.479646
37. Gintzler AR, Schnell SA, Gupta DS, et al. Relationship of spinal dynorphin neurons to delta-opioid receptors and estrogen receptor alpha: anatomical basis for ovarian sex steroid opioid antinociception.J Pharmacol Exp Ther. 2008;326(3):725-31. DOI:10.1124/jpet.108.139816
38. Gintzler AR, Liu NJ. Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems. Transl Res. 2021;234:31-42. DOI:10.1016/j.trsl.2021.02.002
39. Cao DY, Ji Y, Tang B, Traub RJ. Estrogen receptor β activation is antinociceptive in a model of visceral pain in the rat. J Pain. 2012;13(7):685-94. DOI:10.1016/j.jpain.2012.04.010
40. Molina-Martínez LM, Juárez J. Differential expression of μ-opioid receptors in the nucleus accumbens, amygdala and VTA depends on liking for alcohol, chronic alcohol intake and estradiol treatment. Behav Brain Res. 2020;378:112255. DOI:10.1016/j.bbr.2019.112255
41. Farooqui M, Geng ZH, Stephenson EJ, et al. Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells. Mol Cancer Ther. 2006;5(3):611-20.
DOI:10.1158/1535-7163.MCT-05-0016
42. Sapir-Koren R, Livshits G. Rheumatoid arthritis onset in postmenopausal women: Does the ACPA seropositive subset result from genetic effects, estrogen deficiency, skewed profile of CD4(+) T-cells, and their interactions? Mol Cell Endocrinol. 2016;431:145-63. DOI:10.1016/j.mce.2016.05.009
43. Andersson A, Stubelius A, Karlsson MN, et al. Estrogen regulates T helper 17 phenotype and localization in experimental autoimmune arthritis. Arthritis Res Ther. 2015;17(1):32. DOI:10.1186/s13075-015-0548-y
44. Chen RY, Fan YM, Zhang Q, et al. Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter. J Immunol. 2015;194(8):4019-28. DOI:10.4049/jimmunol.1400806
45. Hang X, Zhang Z, Niu R, et al. Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis. J Inflamm Res. 2021;14:843-58. DOI:10.2147/JIR.S295222
46. Qu Q, Jiang S, Li X. Correlation between estrogen receptor-α gene polymorphism and rheumatoid arthritis in females. Panminerva Med. 2020. DOI:10.23736/S0031-0808.19.03806-0
47. Dziedziejko V, Kurzawski M, Safranow K, et al. Oestrogen receptor polymorphisms in female patients with rheumatoid arthritis. Scand J Rheumatol. 2011;40(5):329-33. DOI:10.3109/03009742.2011.563752
________________________________________________
1. Nasonov EL, Yakhno NN, Karateev AE, et al. General principles of treatment for musculoskeletal pain: interdisciplinary consensus. Rheumatology Science and Practice. 2016;54(3):247-65 (in Russian). DOI:10.14412/1995-4484-2016-247-265
2. Watt FE. Musculoskeletal pain and menopause. Post Reprod Health. 2018;24(1):34-43. DOI:10.1177/2053369118757537
3. Adamian LV, Andreeva EN, Apolikhina IA, et al. Menopauza i klimaktericheskoe sostoianie u zhenshchiny. Klinicheskie rekomendatsii. Moscow: Rossiiskoe obshchestvo akusherov-ginekologov, 2021 (in Russian).
4. Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol. 2005;105(5 Pt. 1):1063-73. DOI:10.1097/01.AOG.0000158120.47542.18
5. Ho SC, Chan SG, Yip YB, et al. Menopausal symptoms and symptom clustering in Chinese women. Maturitas. 1999;33(3):219-27. DOI:10.1016/s0378-5122(99)00056-0
6. Bardel A, Wallander MA, Wedel H, Svärdsudd K. Age-specific symptom prevalence in women 35-64 years old: a population-based study. BMC Public Health. 2009;9:37. DOI:10.1186/1471-2458-9-37
7. Horimoto Y, Saito M, Kasumi F. Arthralgia in 329 Patients Taking Aromatase Inhibitors. Breast Care (Basel). 2009;4(5):319-23. DOI:10.1159/000236050
8. Sestak I, Cuzick J, Sapunar F, et al. Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol. 2008;9(9):866-72. DOI:10.1016/S1470-2045(08)70182-7
9. Laroche F, Coste J, Medkour T, et al. Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study. J Pain. 2014;15(3):293-303. DOI:10.1016/j.jpain.2013.11.004
10. Borrie AE, Rose FA, Choi YH, et al. Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients. Breast Cancer Res Treat. 2020;183(2):365-72. DOI:10.1007/s10549-020-05777-1
11. Neeck G, Crofford LJ. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 2000;26(4):989-1002.
DOI:10.1016/s0889-857x(05)70180-0; PMID: 11084955
12. Pamuk ON, Dönmez S, Cakir N. Increased frequencies of hysterectomy and early menopause in fibromyalgia patients: a comparative study. Clin Rheumatol. 2009;28(5):561-4. DOI:10.1007/s10067-009-1087-1
13. Vincent A, Whipple MO, Luedtke CA, et al. Pain and other symptom severity in women with fibromyalgia and a previous hysterectomy. J Pain Res. 2011;4:325-9. DOI:10.2147/JPR.S25490
14. Arslan HS, Nursal AF, Inanir A, et al. Influence of ESR1 Variants on Clinical Characteristics and Fibromyalgia Syndrome in Turkish Women. Endocr Metab Immune Disord Drug Targets. 2021;21(7):1326-32. DOI:10.2174/1871530320666200910110915
15. Koca T, Koçyiğit B, Seyithanoğlu M, Berk E. The Importance of G-protein Coupled Estrogen Receptor in Patients With Fibromyalgia. Arch Rheumatol. 2019;34(4):419-25.
DOI:10.5606/ArchRheumatol.2019.7236
16. Smith SB, Reenilä I, Männistö PT, et al. Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain. 2014;155(11):2390-9. DOI:10.1016/j.pain.2014.09.009
17. Malyala A, Kelly MJ, Rønnekleiv OK. Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes. Steroids. 2005;70(5-7):397-406. DOI:10.1016/j.steroids.2005.03.004
18. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J Comp Neurol. 1997;388(4):507-25.
DOI:10.1002/(sici)1096-9861(19971201)388:4<507::aid-cne1>3.0.co;2-6
19. Zhang W, Wu H, Xu Q, et al. Estrogen modulation of pain perception with a novel 17β-estradiol pretreatment regime in ovariectomized rats. Biol Sex Differ. 2020;11(1):2. DOI:10.1186/s13293-019-0271-5
20. Oshima Y, Matsuda K, Yoshida A, et al. Localization of estrogen receptors alpha and beta in the articular surface of the rat femur. Acta Histochem Cytochem. 2007;40(1):27-34. DOI:10.1267/ahc.06015
21. Carlsten H. Immune responses and bone loss: the estrogen connection. Immunol Rev. 2005;208:194-206. DOI:10.1111/j.0105-2896.2005.00326.x
22. Nilsson BO. Modulation of the inflammatory response by estrogens with focus on the endothelium and its interactions with leukocytes. Inflamm Res. 2007;56(7):269-73. DOI:10.1007/s00011-007-6198-z
23. Ushiyama T, Mori K, Inoue K, et al. Association of oestrogen receptor gene polymorphisms with age at onset of rheumatoid arthritis. Ann Rheum Dis. 1999;58(1):7-10. DOI:10.1136/ard.58.1.7
24. Blanton HL, Barnes RC, McHann MC, et al. Sex differences and the endocannabinoid system in pain. Pharmacol Biochem Behav. 2021;202:173107. DOI:10.1016/j.pbb.2021.173107
25. Yan XJ, Feng CC, Liu Q, et al. Vagal afferents mediate antinociception of estrogen in a rat model of visceral pain: the involvement of intestinal mucosal mast cells and 5-hydroxytryptamine 3 signaling. J Pain. 2014;15(2):204-17. DOI:10.1016/j.jpain.2013.10.012
26. Pecins-Thompson M, Brown NA, Kohama SG, Bethea CL. Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus macaques. J Neurosci. 1996;16(21):7021-9. DOI:10.1523/JNEUROSCI.16-21-07021.1996
27. Bethea CL, Lu NZ, Gundlah C, Streicher JM. Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol. 2002;23(1):41-100. DOI:10.1006/frne.2001.0225
28. Martikainen IK, Hirvonen J, Kajander J, et al. Correlation of human cold pressor pain responses with 5-HT(1A) receptor binding in the brain. Brain Res. 2007;1172:21-31. DOI:10.1016/j.brainres.2007.07.036
29. Osikowicz M, Mika J, Przewlocka B. The glutamatergic system as a target for neuropathic pain relief. Exp Physiol. 2013;98(2):372-84. DOI:10.1113/expphysiol.2012.069922
30. Micevych PE, Mermelstein PG. Membrane estrogen receptors acting through metabotropic glutamate receptors: an emerging mechanism of estrogen action in brain. Mol Neurobiol. 2008;38(1):66-77. DOI:10.1007/s12035-008-8034-z
31. Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696-705. DOI:10.1016/j.tins.2003.09.017
32. Yankova M, Hart SA, Woolley CS. Estrogen increases synaptic connectivity between single presynaptic inputs and multiple postsynaptic CA1 pyramidal cells: a serial electron-microscopic study. Proc Natl Acad Sci USA. 2001;98(6):3525-30. DOI:10.1073/pnas.051624598
33. Castrillon EE, Cairns BE, Wang K, et al. Comparison of glutamate-evoked pain between the temporalis and masseter muscles in men and women. Pain. 2012;153(4):823-9. DOI:10.1016/j.pain.2012.01.003
34. Tashiro A, Okamoto K, Bereiter DA. Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons. Neuroscience. 2009;164(4):1813-20. DOI:10.1016/j.neuroscience.2009.09.058
35. Bäckström T, Haage D, Löfgren M, et al. Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons. Neuroscience. 2011;191:46-54. DOI:10.1016/j.neuroscience.2011.03.061
36. Schweizer-Schubert S, Gordon JL, Eisenlohr-Moul TA, et al. Steroid Hormone Sensitivity in Reproductive Mood Disorders: On the Role of the GABAA Receptor Complex and Stress During Hormonal Transitions. Front Med (Lausanne). 2021;7:479646. DOI:10.3389/fmed.2020.479646
37. Gintzler AR, Schnell SA, Gupta DS, et al. Relationship of spinal dynorphin neurons to delta-opioid receptors and estrogen receptor alpha: anatomical basis for ovarian sex steroid opioid antinociception.J Pharmacol Exp Ther. 2008;326(3):725-31. DOI:10.1124/jpet.108.139816
38. Gintzler AR, Liu NJ. Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems. Transl Res. 2021;234:31-42. DOI:10.1016/j.trsl.2021.02.002
39. Cao DY, Ji Y, Tang B, Traub RJ. Estrogen receptor β activation is antinociceptive in a model of visceral pain in the rat. J Pain. 2012;13(7):685-94. DOI:10.1016/j.jpain.2012.04.010
40. Molina-Martínez LM, Juárez J. Differential expression of μ-opioid receptors in the nucleus accumbens, amygdala and VTA depends on liking for alcohol, chronic alcohol intake and estradiol treatment. Behav Brain Res. 2020;378:112255. DOI:10.1016/j.bbr.2019.112255
41. Farooqui M, Geng ZH, Stephenson EJ, et al. Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells. Mol Cancer Ther. 2006;5(3):611-20.
DOI:10.1158/1535-7163.MCT-05-0016
42. Sapir-Koren R, Livshits G. Rheumatoid arthritis onset in postmenopausal women: Does the ACPA seropositive subset result from genetic effects, estrogen deficiency, skewed profile of CD4(+) T-cells, and their interactions? Mol Cell Endocrinol. 2016;431:145-63. DOI:10.1016/j.mce.2016.05.009
43. Andersson A, Stubelius A, Karlsson MN, et al. Estrogen regulates T helper 17 phenotype and localization in experimental autoimmune arthritis. Arthritis Res Ther. 2015;17(1):32. DOI:10.1186/s13075-015-0548-y
44. Chen RY, Fan YM, Zhang Q, et al. Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter. J Immunol. 2015;194(8):4019-28. DOI:10.4049/jimmunol.1400806
45. Hang X, Zhang Z, Niu R, et al. Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis. J Inflamm Res. 2021;14:843-58. DOI:10.2147/JIR.S295222
46. Qu Q, Jiang S, Li X. Correlation between estrogen receptor-α gene polymorphism and rheumatoid arthritis in females. Panminerva Med. 2020. DOI:10.23736/S0031-0808.19.03806-0
47. Dziedziejko V, Kurzawski M, Safranow K, et al. Oestrogen receptor polymorphisms in female patients with rheumatoid arthritis. Scand J Rheumatol. 2011;40(5):329-33. DOI:10.3109/03009742.2011.563752