Serum Inflammatory Marker Changes in Women with Uterine Fibroids before and after Treatment
Abstract
This study aimed to assess the clinical symptoms associated with UFs and to evaluate dynamic, longitudinal changes in serum inflammatory markers before and after treatment in women diagnosed with UFs compared with healthy controls.
In this retrospective observational study, 90 women including 60 women diagnosed with UFs and 30 age-matched healthy controls. Uterine fibroids were confirmed by ultrasonography and histopathology. Serum levels of tumor necrosis factor α (TNF-α), interferon β (IFN-β), IFN-γ, C-reactive protein (CRP), and basic fibroblast growth factor (FGF) were measured using standardized enzyme-linked immunosorbent assay kits. Lymphocyte subsets were analyzed via flow cytometry. Patients with UFs underwent medical or surgical treatment based on clinical indications, and inflammatory markers were reassessed 3 months posttreatment.
There were various symptoms such as pelvic pain (66.67%), abnormal bleeding (66.67%), organ-compression symptoms (45%), infertility (26.67%), and miscarriage (18.33%) compared with controls. Women diagnosed with UFs showed a higher lymphocyte count, proinflammatory mediators, and decreased level of interleukins as compared with the healthy population of females.
The observed dynamic pretreatment and posttreatment shifts in serum inflammatory markers suggest involvement of adaptive immunity and angiogenic pathways, highlighting the potential role of inflammatory regulation in improving reproductive outcomes, including preparation for assisted reproductive technologies.
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2. Leppert PC, Al-Hendy A, Baird DD, Catherino WH, Stewart EA, Laughlin-Tommaso SK, et al. Summary of the proceedings of the Basic Science of Uterine Fibroids meeting: new developments. FS Sci. 2021;2(1):88–100.
3. Ciebiera M, Ali M, Prince L, Włodarczyk M, Zgliczyński S, Skrzypczak J, et al. Natural compounds in the medical treatment of uterine fibroids. J Clin Med. 2020;9(5):1479.
4. Islam MS, Afrin S, Jones SI, Segars JH, Leppert PC, Al-Hendy A, et al. Selective progesterone receptor modulators: mechanisms and therapeutic utility. Endocr Rev. 2020;41(5):bnaa012.
5. Szydłowska I, Grabowska M, Nawrocka-Rutkowska J, Czernobilsky B, Zajdel K, Pietrowski D, et al. Markers of proliferation, apoptosis and fibrosis in ulipristal acetate–treated uterine fibroids. J Clin Med. 2021;10(4):562.
6. Tinelli A, Kosmas IP, Mynbaev OA, Sparic R, Al-Hendy A, Malvasi A, et al. Biological impact of ulipristal acetate on uterine leiomyoma growth. Curr Pharm Des. 2020;26(3):310–7.
7. Lewis TD, Malik M, Britten J, Catherino WH, Leppert PC, Segars JH, et al. Ulipristal acetate decreases active TGF-β3 signaling in uterine leiomyoma. Fertil Steril. 2019;111(4):806–15.
8. Courtoy GE, Henriet P, Marbaix E, Defrère S, Lemoine P, Emonard H, et al. Matrix metalloproteinase activity correlates with uterine myoma reduction. J Clin Endocrinol Metab. 2018;103(4):1566–73.
9. AlAshqar A, Patzkowsky K, Afrin S, Wild RA, Taylor HS, Borahay MA, et al. Cardiometabolic risk factors and benign gynecologic disorders. Obstet Gynecol Surv. 2019;74(11):661–73.
10. Steen EH, Wang X, Balaji S, Butte MJ, Bollyky PL, Keswani SG, et al. Interleukin-10 in tissue fibrosis. Adv Wound Care (New Rochelle). 2020;9(4):184–98.
11. Faraji A, Shamsadinimoghadam R, Jahromi MA, Rezaei A, Rezaei F, Ghasemi M, et al. TGF-β1 in uterine leiomyoma and endometrial polyp. Obstet Gynecol Sci. 2021;64:107–13.
12. Ciebiera M, Włodarczyk M, Wrzosek M, Wojtyła C, Łukaszuk K, Nowicka G, et al. Role of transforming growth factor β in uterine fibroids. Int J Mol Sci. 2017;18(11):2435.
13. Sevostyanova O, Lisovskaya T, Chistyakova G, Kazakova T, Lysenko E, Orlova N, et al. Proinflammatory mediators and reproductive failure in uterine fibroids. Gynecol Endocrinol. 2020;36(Suppl 1):33–5.
14. Sohn GS, Cho S, Kim YM, Cho CH, Kim MR, Lee SR, et al. Current medical treatment of uterine fibroids. Obstet Gynecol Sci. 2018;61(2):192–201.
15. Borahay MA, Asoglu MR, Mas A, Kilic GS, Adam S, Al-Hendy A, et al. Estrogen receptors and signaling in fibroids. Reprod Sci. 2017;24(9):1235–44.
16. Konenkov VI, Koroleva EG, Orlov NB, Prokofiev VY, Novikov AM, Dergacheva TI, et al. Proinflammatory cytokines in uterine myoma. Bull Exp Biol Med. 2018;165:698–701.
17. Islam MS, Greco S, Janjusevic M, Leppert PC, Al-Hendy A, Segars JH, et al. Growth factors and uterine fibroid pathogenesis. Best Pract Res Clin Obstet Gynaecol. 2016;34:25–36.
18. Yang Q, Ciebiera M, Bariani MV, Ali M, Elkafas H, Boyer TG, et al. Uterine fibroids: origin, pathogenesis and treatment. Endocr Rev. 2022;43(4):678–719.
19. Marsh EE, Wegienka G, Williams DR. Uterine fibroids. JAMA. 2024;331(17):1492–3.
20. Coutinho LM, Assis WA, Spagnuolo-Souza A, Reis FM, Brum IS, Soares JM, et al. Uterine fibroids and pregnancy. Reprod Sci. 2022;29(8):2145–51.Aninye IO, Laitner MH, Society for Women's Health Research Uterine Fibroids Working Group. Uterine fibroids: assessing unmet needs from bench to bedside. J Women Health. 2021;30(8):1060-7.
21. Aninye IO, Laitner MH, Stewart EA, Laughlin-Tommaso SK, Catherino WH, Leppert PC, et al. Uterine fibroids: assessing unmet needs from bench to bedside. J Womens Health (Larchmt). 2021;30(8):1060–7.
22. Katon JG, Plowden TC, Marsh EE, Wegienka G, Williams DR, Wise LA, et al. Racial disparities in uterine fibroids and endometriosis. Fertil Steril. 2023;119(3):355–63.
23. Kwas K, Nowakowska A, Fornalczyk A, Kuc P, Kuczyński W, Ciebiera M, et al. Impact of contraception on uterine fibroids. Medicina (Kaunas). 2021;57(7):717.
24. Landman AJ, Don EE, Vissers G, Ket HC, Oudijk MA, de Groot CJ, et al. Risk of preterm birth in women with uterine fibroids. PLoS One. 2022;17(6):e0269478.
25. AlAshqar A, Lulseged B, Mason-Otey A, Borahay MA, Taylor HS, Wild RA, et al. Oxidative stress and antioxidants in uterine fibroids. Antioxidants (Basel). 2023;12(4):807.
26. Li H, Hu Z, Fan Y, Hao Y, Zhang X, Wang Y, et al. Influence of uterine fibroids on adverse pregnancy outcomes. BMC Pregnancy Childbirth. 2024;24(1):345.
27. Vannuccini S, Petraglia F, Carmona F, Calaf J, Chapron C, Bulun SE, et al. Management of fibroid-related abnormal uterine bleeding. Fertil Steril. 2024.
28. Qin H, Lin Z, Vásquez E, Wei Y, Li Y, Zhou Y, et al. Association between obesity and uterine fibroids. J Epidemiol Community Health. 2021;75(2):197–204.
29. Micić J, Macura M, Andjić M, Radulović D, Popović J, Janković S, et al. Available treatment modalities for uterine fibroids. Medicina (Kaunas). 2024;60(6):868.
30. Lakshmi SS, Sarella PN, Adarsh K, Reddy PS, Rao VM, Kumar A, et al. Concurrent diagnosis of renal calculi, uterine fibroids and ovarian cysts. J Clin Pharm Res. 2023:22–7.
31. Datir SG, Bhake A, Datir IS, Kulkarni P, Deshpande R, Joshi A, et al. Management of uterine fibroids and complications during pregnancy. Cureus. 2022;14(11).
32. Amoah A, Joseph N, Reap S, Stewart EA, Laughlin-Tommaso SK, Leppert PC, et al. Appraisal of uterine fibroid management guidelines. BJOG. 2022;129(3):356–64.
33. Cheng LC, Li HY, Gong QQ, Wang Y, Zhang J, Liu X, et al. Global burden of uterine fibroids from 1990 to 2019. Front Med (Lausanne). 2022;9:1003605.
34. Islam MS, Afrin S, Singh B, Janjusevic M, Leppert PC, Al-Hendy A, et al. Extracellular matrix and Hippo signaling as therapeutic targets. Clin Transl Med. 2021;11(7):e475.
35. Anneveldt KJ, van’t Oever HJ, Nijholt IM, Franx A, Hehenkamp WJK, Brölmann HAM, et al. Reproductive outcomes after high-intensity focused ultrasound. Eur J Radiol. 2021;141:109801.
36. Tîrnovanu MC, Lozneanu L, Tîrnovanu ŞD, Căruntu ID, Bălan R, Costăchescu G, et al. Uterine fibroids and pregnancy. Healthcare (Basel). 2022;10(5):855.
37. Uimari O, Nazri H, Tapmeier T, Missmer SA, Becker CM, Zondervan KT, et al. Endometriosis and uterine fibroids. Front Reprod Health. 2021;3:750018.
38. Ali M, Ciebiera M, Vafaei S, Elkafas H, Yang Q, Boyer TG, et al. Progesterone signaling in uterine fibroid pathogenesis. Cells. 2023;12(8):1117.
39. Bhat RG, Rao BK, Patil S, Kulkarni A, Desai S, Joshi R, et al. Gut microbiota in uterine fibroid pathogenesis. Reprod Sci. 2023;30(12):3443–55.
40. Cianci S, Gulino FA, Palmara V, Vitale SG, Caruso S, Guglielmino MR, et al. Surgical strategies for uterine fibroid treatment. Medicina (Kaunas). 2023;60(1):64.
41. Prokofiev V, Konenkov V, Koroleva E, Shevchenko A, Dergacheva T, Novikov A, et al. Cytokine gene network structure in uterine fibroids. In: Proc CSGB. 2020:261–4.
42. Ishikawa H, Goto Y, Hirooka C, Sato K, Takeda S, Shibata K, et al. Inflammation and immune response in uterine fibroids. J Reprod Immunol. 2024:104317.
43. Ben-Nagi J, Miell J, Mavrelos D, Naftalin J, Hoo W, Jurkovic D, et al. Endometrial implantation factors in submucous fibroids. Reprod Biomed Online. 2010;21(5):610–5.
44. Navarro A, Bariani MV, Yang Q, Elkafas H, Ali M, Boyer TG, et al. Impact of uterine fibroids on endometrium function. Front Cell Dev Biol. 2021;9:633180.
45. Altukhova OB, Radzinsky VE, Sirotina SS, Koroleva EG, Konenkov VI, Orlov NB, et al. Interleukin gene polymorphism and uterine fibroid risk. Obstet Gynecol. 2022;(7):81–7.
2. Leppert PC, Al-Hendy A, Baird DD, Catherino WH, Stewart EA, Laughlin-Tommaso SK, et al. Summary of the proceedings of the Basic Science of Uterine Fibroids meeting: new developments. FS Sci. 2021;2(1):88–100.
3. Ciebiera M, Ali M, Prince L, Włodarczyk M, Zgliczyński S, Skrzypczak J, et al. Natural compounds in the medical treatment of uterine fibroids. J Clin Med. 2020;9(5):1479.
4. Islam MS, Afrin S, Jones SI, Segars JH, Leppert PC, Al-Hendy A, et al. Selective progesterone receptor modulators: mechanisms and therapeutic utility. Endocr Rev. 2020;41(5):bnaa012.
5. Szydłowska I, Grabowska M, Nawrocka-Rutkowska J, Czernobilsky B, Zajdel K, Pietrowski D, et al. Markers of proliferation, apoptosis and fibrosis in ulipristal acetate–treated uterine fibroids. J Clin Med. 2021;10(4):562.
6. Tinelli A, Kosmas IP, Mynbaev OA, Sparic R, Al-Hendy A, Malvasi A, et al. Biological impact of ulipristal acetate on uterine leiomyoma growth. Curr Pharm Des. 2020;26(3):310–7.
7. Lewis TD, Malik M, Britten J, Catherino WH, Leppert PC, Segars JH, et al. Ulipristal acetate decreases active TGF-β3 signaling in uterine leiomyoma. Fertil Steril. 2019;111(4):806–15.
8. Courtoy GE, Henriet P, Marbaix E, Defrère S, Lemoine P, Emonard H, et al. Matrix metalloproteinase activity correlates with uterine myoma reduction. J Clin Endocrinol Metab. 2018;103(4):1566–73.
9. AlAshqar A, Patzkowsky K, Afrin S, Wild RA, Taylor HS, Borahay MA, et al. Cardiometabolic risk factors and benign gynecologic disorders. Obstet Gynecol Surv. 2019;74(11):661–73.
10. Steen EH, Wang X, Balaji S, Butte MJ, Bollyky PL, Keswani SG, et al. Interleukin-10 in tissue fibrosis. Adv Wound Care (New Rochelle). 2020;9(4):184–98.
11. Faraji A, Shamsadinimoghadam R, Jahromi MA, Rezaei A, Rezaei F, Ghasemi M, et al. TGF-β1 in uterine leiomyoma and endometrial polyp. Obstet Gynecol Sci. 2021;64:107–13.
12. Ciebiera M, Włodarczyk M, Wrzosek M, Wojtyła C, Łukaszuk K, Nowicka G, et al. Role of transforming growth factor β in uterine fibroids. Int J Mol Sci. 2017;18(11):2435.
13. Sevostyanova O, Lisovskaya T, Chistyakova G, Kazakova T, Lysenko E, Orlova N, et al. Proinflammatory mediators and reproductive failure in uterine fibroids. Gynecol Endocrinol. 2020;36(Suppl 1):33–5.
14. Sohn GS, Cho S, Kim YM, Cho CH, Kim MR, Lee SR, et al. Current medical treatment of uterine fibroids. Obstet Gynecol Sci. 2018;61(2):192–201.
15. Borahay MA, Asoglu MR, Mas A, Kilic GS, Adam S, Al-Hendy A, et al. Estrogen receptors and signaling in fibroids. Reprod Sci. 2017;24(9):1235–44.
16. Konenkov VI, Koroleva EG, Orlov NB, Prokofiev VY, Novikov AM, Dergacheva TI, et al. Proinflammatory cytokines in uterine myoma. Bull Exp Biol Med. 2018;165:698–701.
17. Islam MS, Greco S, Janjusevic M, Leppert PC, Al-Hendy A, Segars JH, et al. Growth factors and uterine fibroid pathogenesis. Best Pract Res Clin Obstet Gynaecol. 2016;34:25–36.
18. Yang Q, Ciebiera M, Bariani MV, Ali M, Elkafas H, Boyer TG, et al. Uterine fibroids: origin, pathogenesis and treatment. Endocr Rev. 2022;43(4):678–719.
19. Marsh EE, Wegienka G, Williams DR. Uterine fibroids. JAMA. 2024;331(17):1492–3.
20. Coutinho LM, Assis WA, Spagnuolo-Souza A, Reis FM, Brum IS, Soares JM, et al. Uterine fibroids and pregnancy. Reprod Sci. 2022;29(8):2145–51.Aninye IO, Laitner MH, Society for Women's Health Research Uterine Fibroids Working Group. Uterine fibroids: assessing unmet needs from bench to bedside. J Women Health. 2021;30(8):1060-7.
21. Aninye IO, Laitner MH, Stewart EA, Laughlin-Tommaso SK, Catherino WH, Leppert PC, et al. Uterine fibroids: assessing unmet needs from bench to bedside. J Womens Health (Larchmt). 2021;30(8):1060–7.
22. Katon JG, Plowden TC, Marsh EE, Wegienka G, Williams DR, Wise LA, et al. Racial disparities in uterine fibroids and endometriosis. Fertil Steril. 2023;119(3):355–63.
23. Kwas K, Nowakowska A, Fornalczyk A, Kuc P, Kuczyński W, Ciebiera M, et al. Impact of contraception on uterine fibroids. Medicina (Kaunas). 2021;57(7):717.
24. Landman AJ, Don EE, Vissers G, Ket HC, Oudijk MA, de Groot CJ, et al. Risk of preterm birth in women with uterine fibroids. PLoS One. 2022;17(6):e0269478.
25. AlAshqar A, Lulseged B, Mason-Otey A, Borahay MA, Taylor HS, Wild RA, et al. Oxidative stress and antioxidants in uterine fibroids. Antioxidants (Basel). 2023;12(4):807.
26. Li H, Hu Z, Fan Y, Hao Y, Zhang X, Wang Y, et al. Influence of uterine fibroids on adverse pregnancy outcomes. BMC Pregnancy Childbirth. 2024;24(1):345.
27. Vannuccini S, Petraglia F, Carmona F, Calaf J, Chapron C, Bulun SE, et al. Management of fibroid-related abnormal uterine bleeding. Fertil Steril. 2024.
28. Qin H, Lin Z, Vásquez E, Wei Y, Li Y, Zhou Y, et al. Association between obesity and uterine fibroids. J Epidemiol Community Health. 2021;75(2):197–204.
29. Micić J, Macura M, Andjić M, Radulović D, Popović J, Janković S, et al. Available treatment modalities for uterine fibroids. Medicina (Kaunas). 2024;60(6):868.
30. Lakshmi SS, Sarella PN, Adarsh K, Reddy PS, Rao VM, Kumar A, et al. Concurrent diagnosis of renal calculi, uterine fibroids and ovarian cysts. J Clin Pharm Res. 2023:22–7.
31. Datir SG, Bhake A, Datir IS, Kulkarni P, Deshpande R, Joshi A, et al. Management of uterine fibroids and complications during pregnancy. Cureus. 2022;14(11).
32. Amoah A, Joseph N, Reap S, Stewart EA, Laughlin-Tommaso SK, Leppert PC, et al. Appraisal of uterine fibroid management guidelines. BJOG. 2022;129(3):356–64.
33. Cheng LC, Li HY, Gong QQ, Wang Y, Zhang J, Liu X, et al. Global burden of uterine fibroids from 1990 to 2019. Front Med (Lausanne). 2022;9:1003605.
34. Islam MS, Afrin S, Singh B, Janjusevic M, Leppert PC, Al-Hendy A, et al. Extracellular matrix and Hippo signaling as therapeutic targets. Clin Transl Med. 2021;11(7):e475.
35. Anneveldt KJ, van’t Oever HJ, Nijholt IM, Franx A, Hehenkamp WJK, Brölmann HAM, et al. Reproductive outcomes after high-intensity focused ultrasound. Eur J Radiol. 2021;141:109801.
36. Tîrnovanu MC, Lozneanu L, Tîrnovanu ŞD, Căruntu ID, Bălan R, Costăchescu G, et al. Uterine fibroids and pregnancy. Healthcare (Basel). 2022;10(5):855.
37. Uimari O, Nazri H, Tapmeier T, Missmer SA, Becker CM, Zondervan KT, et al. Endometriosis and uterine fibroids. Front Reprod Health. 2021;3:750018.
38. Ali M, Ciebiera M, Vafaei S, Elkafas H, Yang Q, Boyer TG, et al. Progesterone signaling in uterine fibroid pathogenesis. Cells. 2023;12(8):1117.
39. Bhat RG, Rao BK, Patil S, Kulkarni A, Desai S, Joshi R, et al. Gut microbiota in uterine fibroid pathogenesis. Reprod Sci. 2023;30(12):3443–55.
40. Cianci S, Gulino FA, Palmara V, Vitale SG, Caruso S, Guglielmino MR, et al. Surgical strategies for uterine fibroid treatment. Medicina (Kaunas). 2023;60(1):64.
41. Prokofiev V, Konenkov V, Koroleva E, Shevchenko A, Dergacheva T, Novikov A, et al. Cytokine gene network structure in uterine fibroids. In: Proc CSGB. 2020:261–4.
42. Ishikawa H, Goto Y, Hirooka C, Sato K, Takeda S, Shibata K, et al. Inflammation and immune response in uterine fibroids. J Reprod Immunol. 2024:104317.
43. Ben-Nagi J, Miell J, Mavrelos D, Naftalin J, Hoo W, Jurkovic D, et al. Endometrial implantation factors in submucous fibroids. Reprod Biomed Online. 2010;21(5):610–5.
44. Navarro A, Bariani MV, Yang Q, Elkafas H, Ali M, Boyer TG, et al. Impact of uterine fibroids on endometrium function. Front Cell Dev Biol. 2021;9:633180.
45. Altukhova OB, Radzinsky VE, Sirotina SS, Koroleva EG, Konenkov VI, Orlov NB, et al. Interleukin gene polymorphism and uterine fibroid risk. Obstet Gynecol. 2022;(7):81–7.
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| Keywords | ||
| Chronic inflammation Inflammatory markers Lymphocyte subsets Serum TNF-α Uterine fibroids | ||
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How to Cite
1.
Huang Y, Yang W, Wang S, Yang S. Serum Inflammatory Marker Changes in Women with Uterine Fibroids before and after Treatment. Iran J Allergy Asthma Immunol. 2026;:1-11.
