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Evaluation of goserelin effectiveness based on assessment of inflammatory cytokines and symptoms in uterine leiomyoma

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Abstract

Background Uterine leiomyoma is a benign tumour of the uterine smooth muscles associated with an elevated level of inflammatory cytokines. Goserelin, a synthetic gonadotropin-releasing hormone analogue, suppresses the production of sex hormones and release of inflammatory cytokines in uterine leiomyoma cells. Objective The primary objective of this study was to find out the effectiveness of subcutaneous goserelin therapy on lowering serum levels of inflammatory cytokines and improving uterine leiomyoma-related symptoms in female patients diagnosed with uterine leiomyoma. The secondary objective was to assess the tolerability to goserelin therapy used in the management of this tumour. Setting Outpatient gynaecological clinic of the medical consultation department of Baghdad Teaching Hospital, Baghdad province, Iraq. Methods A single centre, prospective, longitudinal, cohort study was carried out on female patients diagnosed with uterine leiomyoma. Goserelin 3.6 mg subcutaneous injection was given in a consecutive monthly dose for the total time duration of three months. Serum levels of inflammatory cytokines, tumour necrosis factor-α and monocyte chemotactic protein-1 were detected before and after goserelin therapy in a consecutive monthly assessment. The study also assessed the improvement in uterine leiomyoma-related symptoms, including pelvic pain alongside the incidence of goserelin-related side effects during therapy schedules. Main Outcome Measures Assessment of serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 alongside uterine leiomyoma-related symptoms, including pelvic pain and goserelin-related side effects. Results There was a significant decrease in serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 compared to the baseline level over the 3-month duration of goserelin therapy (0.11 ± 0.02 vs. 0.74 ± 0.19) pg/mL; (0.07 ± 0.00 vs. 0.44 ± 0.18) pg/mL respectively. Patients showed a clinical improvement regarding uterine leiomyoma-related symptoms following each of the consecutive monthly doses of goserelin therapy (n = 11, 55%, P < 0.0001; n = 15, 75%, P < 0.0001; n = 18, 90%, P < 0.0001) respectively. This also includes a significant decrease in the intensity of leiomyoma-related pelvic pain before and after goserelin therapy (7.2 ± 1.43 vs. 3.05 ± 1.14, P < 0.0001). The majority of patients reported vaginal dryness (60%) as the main goserelin-related side effect. Conclusion Goserelin therapy reduces serum levels of inflammatory cytokines, tumour necrosis factor- α and monocyte chemotactic protein-1, improving leiomyoma-related symptoms with good tolerability in patients with uterine leiomyoma.

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References

  1. Khan AT, Shehmar M, Gupta JK. Uterine fibroids: current perspectives. Int J Womens Health. 2014;6:95–114

    Article  Google Scholar 

  2. Fleischer R, Weston GC, Vollenhoven BJ, Rogers PA. Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation. Best Pract Res Clin Obstet Gynaecol. 2008;22:603–14

    Article  Google Scholar 

  3. Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 2008;22:571–88

    Article  Google Scholar 

  4. Cardozo ER, Clark AD, Banks NK, Henne MB, Stegmann BJ, Segars JH. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol. 2012;206(211):e1–9

    Google Scholar 

  5. Bulun SE. Uterine fibroids. N Engl J Med. 2013;369:1344–55

    Article  CAS  Google Scholar 

  6. Chegini N. Proinflammatory and profibrotic mediators: principal effectors of leiomyoma development as a fibrotic. Semin Reprod Med. 2010;28:180–203

    Article  CAS  Google Scholar 

  7. Wang Y, Feng G, Wang J, Zhou Y, Liu Y, Shi Y, et al. Differential effects of tumor necrosis factor-α on matrix metalloproteinase-2 expression in human myometrial and uterine leiomyoma smooth muscle cells. Hum Reprod. 2015;30:61–70

    Article  Google Scholar 

  8. Pfeffer K. Biological functions of tumor necrosis factor cytokines and their receptors. Cytokine Growth Factor Rev. 2003;14:185–91

    Article  CAS  Google Scholar 

  9. Kusano KF, Nakamura K, Kusano H, Nishii N, Banba K, Ikeda T, et al. Significance of the level of monocyte chemoattractant protein-1 in human atherosclerosis. Circ J. 2004;68:671–6

    Article  CAS  Google Scholar 

  10. Xia M, Sui Z. Recent developments in CCR2 antagonists. Expert Opin Ther Pat. 2009;19:295–303

    Article  CAS  Google Scholar 

  11. Commandeur AE, Styer AK, Teixeira JM. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. Hum Reprod Update. 2015;21:593–615

    Article  CAS  Google Scholar 

  12. Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol. 2004;104:393–406

    Article  Google Scholar 

  13. Magon N. Gonadotropin releasing hormone agonists: expanding vistas. Indian J Endocrinol Metab. 2011;15:261–7

    Article  CAS  Google Scholar 

  14. Perry CM, Brogden RN. Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in benign gynaecological disorders. Drugs. 1996;51:319–46

    Article  CAS  Google Scholar 

  15. Pelvic pain assessment form-old version 2004-English. International Pelvic Pain Society. https://www.pelvicpain.org/IPPS/Professional/Documents-Forms/IPPS/Content/Professional/Documents_and_Forms.aspx?hkey=2597ab99-df83-40ee-89cd-7bd384efed19. Accessed 24 Dec 2019

  16. Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril. 2007;87:725–36

    Article  Google Scholar 

  17. Sato F, Mori M, Nishi M, Kudo R, Miyake H. Familial aggregation of uterine myomas in Japanese women. J Epidemiol. 2002;12:249–53

    Article  Google Scholar 

  18. Van Voorhis BJ, Romitti PA, Jones MP. Family history as a risk factor for development of uterine leiomyomas. Results of a pilot study. J Reprod Med. 2002;47:663–9

    PubMed  Google Scholar 

  19. Flake GP, Moore AB, Sutton D, Kissling GE, Horton J, Wicker B, et al. The natural history of uterine leiomyomas: light and electron microscopic studies of fibroid phases, interstitial ischemia, inanosis, and reclamation. Obstet Gynecol Int. 2013;2013:528376

    PubMed  PubMed Central  Google Scholar 

  20. Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 2013;34:130–62

    Article  CAS  Google Scholar 

  21. Balkwill F. Tumour necrosis factor and cancer. Nat Rev Cancer. 2009;9:361–71

    Article  CAS  Google Scholar 

  22. Maruo T, Ohara N, Wang J, Matsuo H. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. Hum Reprod Update. 2004;10:207–20

    Article  CAS  Google Scholar 

  23. Suzuki M, Takamizawa S, Nomaguchi K, Suzu S, Yamada M, Igarashi T, et al. Erythropoietin synthesis by tumour tissues in a patient with uterine myoma and erythrocytosis. Br J Haematol. 2001;113:49–51

    Article  CAS  Google Scholar 

  24. Kurachi O, Matsuo H, Samoto T, Maruo T. Tumor necrosis factor-α expression in human uterine leiomyoma and its down-regulation by progesterone. J Clin Endocrinol Metab. 2001;86:2275–80

    CAS  PubMed  Google Scholar 

  25. Ciebiera M, Włodarczyk M, Wrzosek M, Wojtyła C, Błażej M, Nowicka G, et al. TNF-α serum levels are elevated in women with clinically symptomatic uterine fibroids. Int J Immunopathol Pharmacol. 2018. https://doi.org/10.1177/2058738418779461

    Article  PubMed  PubMed Central  Google Scholar 

  26. Negus RP, Stamp GW, Relf MG, Burke F, Malik ST, Bernasconi S, et al. The detection and localization of monocyte chemoattractant ~ rotein-1 (MCP-1) in human ovarian cancer. J Clin Invest. 1995;95:2391–6

    Article  CAS  Google Scholar 

  27. Meresman GF, Bilotas MA, Lombardi E, Tesone M, Sueldo C, Barañao RI. Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod. 2003;18:1767–71

    Article  CAS  Google Scholar 

  28. Chegini N, Verala J, Luo X, Xu J, Williams RS. Gene expression profile of leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy. J Soc Gynecol Investig. 2003;10:161–71

    Article  CAS  Google Scholar 

  29. Luo X, Ding L, Xu J, Williams RS, Chegini N. Leiomyoma and myometrial gene expression profiles and their responses to gonadotropin-releasing hormone analog therapy. Endocrinology. 2005;146:1074–96

    Article  CAS  Google Scholar 

  30. Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005;308:1589–92

    Article  CAS  Google Scholar 

  31. Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, et al. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod. 2010;25:642–53

    Article  CAS  Google Scholar 

  32. Matsui S, Yasui T, Uemura H, Yamamoto S, Matsuzaki T, Tsuchiya N, et al. Induction of circulating monocyte chemoattractant protein-1 in women with gonadotropin-releasing hormone agonist. J Reprod Immunol. 2011;90:227–34

    Article  CAS  Google Scholar 

  33. Lumsden MA, West CP, Thomas E, Coutts J, Hillier H, Thomas N, et al. Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids. Br J Obstet Gynaecol. 1994;101:438–42

    Article  CAS  Google Scholar 

  34. Duffy S. Chronic pelvic pain: defining the scope of the problem. Int J Gynaecol Obstet. 2001;74:S3–7

    Article  Google Scholar 

  35. Weijenborg PT, Greeven A, Dekker FW, Peters AA, Ter Kuile MM. Clinical course of chronic pelvic pain in women. Pain. 2007;132:S117–S12323

    Article  Google Scholar 

  36. Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril. 1993;60:75–9

    Article  CAS  Google Scholar 

  37. Soysal ME, Soysal S, Vicdan K, Ozer S. A randomized controlled trial of goserelin and medroxyprogesterone acetate in the treatment of pelvic congestion. Hum Reprod. 2001;16:931–9

    Article  CAS  Google Scholar 

  38. West CP, Lumsden MA, Lawson S, Williamson J, Baird DT. Shrinkage of uterine fibroids during therapy with goserelin (Zoladex): a luteinizing hormone-releasing hormone agonist administered as a monthly subcutaneous depot. Fertil Steril. 1987;48:45–51

    Article  CAS  Google Scholar 

  39. Al-Taie A, Köseoğlu A. Incidence of early related–complications of port-A catheter and impact of clinical pharmacist participation and counselling outcomes. J Young Pharm. 2018;10:218–21

    Article  Google Scholar 

  40. Al-Taie A, Köseoğlu A. Determination of radiotherapy-related acute side effects; a starting point for the possible implementation of a clinical pharmacy services in the radiological unit in turkey. J Young Pharm. 2019;11:434–8

    Article  Google Scholar 

  41. Al-Taie A, Abdulrazzaq HA, Yılmaz ZK, Izzettin FV, Koramaz N, Yılmaz KC. Differences in patients' self-reporting types to adverse symptomatic events. Eur J Clin Pharm. 2016;18:130–5

    Google Scholar 

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Acknowledgement

The authors would like to express their gratitude to Dr Athmar Dhahir Al-shahoani for her help and valuable suggestions.

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Mohammed, N.H., Al-Taie, A. & Albasry, Z. Evaluation of goserelin effectiveness based on assessment of inflammatory cytokines and symptoms in uterine leiomyoma. Int J Clin Pharm 42, 931–937 (2020). https://doi.org/10.1007/s11096-020-01030-3

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