Vol 95, No 6 (2024)
Research paper
Published online: 2024-01-15

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Evaluation of the risk of thyroid cancer following hysterectomy through meta-analysis

Ozkan Balcin12, Ilker Ercan3, Arda Uzunoglu2
Pubmed: 38334350
Ginekol Pol 2024;95(6):434-442.


Objectives: Thyroid cancer is observed more frequently in women than men, possibly due to the influence of hormonal factors. This study aims to conduct a meta-analysis encompassing both prospective and retrospective observational studies to examine the risk of thyroid cancer in women who have undergone hysterectomy surgery. Material and methods: The literature search identified 356 articles by May 2022, and eight reported hazard ratios for thyroid cancer in women who underwent hysterectomy surgery. After the eliminations, we performed three different meta-analyses with studies that included patients who underwent only total abdominal hysterectomy (TAH), total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO), and underwent hysterectomy with or without BSO. The reporting of this study has been conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality of Systematic Reviews). Results: Our study showcases a comprehensive meta-analysis that includes eight observational studies, both retrospective and prospective, exploring the link between hysterectomy and the likelihood of developing thyroid cancer. This analysis is based on data from more than 12 million individuals, encompassing over 24,000 cases. Women who had undergone TAH (HR = 1.586, 95% CI: 1.382–1.819, p < 0.001), women who had undergone TAH and BSO (HR = 1.420, 95% CI: 1.205–1.675, p < 0.001), and women who had undergone hysterectomy with or without BSO had an increased risk (HR = 1.623, 95% CI: 1.387–1.899, p < 0.001) of developing thyroid cancer later in life. Conclusions: We found that hysterectomy had a statistically significant risk effect on the development of thyroid cancer. The limited number of previous studies, the low amount of information, the lack of homogeneous distribution of the patients in the studies, and the unknown characteristics of thyroid cancer developing after hysterectomy were the limitations of this study. Nevertheless, our findings can positively affect public health because of the potential to enlighten the etiological mechanisms leading to thyroid cancer. Future researches should first aim to explain the underlying mechanisms of developing thyroid cancer after hysterectomy.

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  1. Fitzmaurice C, Dicker D, Pain A, et al. Global Burden of Disease Cancer Collaboration. The global burden of cancer 2013. JAMA Oncol. 2015; 1(4): 505–527.
  2. Lubitz CC, Kong CY, McMahon PM, et al. Annual financial impact of well-differentiated thyroid cancer care in the United States. Cancer. 2014; 120(9): 1345–1352.
  3. Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin. 2013; 63(6): 374–394.
  4. Colonna M, Uhry Z, Guizard AV, et al. FRANCIM network. Recent trends in incidence, geographical distribution, and survival of papillary thyroid cancer in France. Cancer Epidemiol. 2015; 39(4): 511–518.
  5. Clavel-Chapelon F, Guillas G, Tondeur L, et al. Risk of differentiated thyroid cancer in relation to adult weight, height and body shape over life: the French E3N cohort. Int J Cancer. 2010; 126(12): 2984–2990.
  6. Trésallet C, Seman M, Tissier F, et al. The incidence of papillary thyroid carcinoma and outcomes in operative patients according to their body mass indices. Surgery. 2014; 156(5): 1145–1152.
  7. Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncol. 2010; 6(11): 1771–1779.
  8. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5): E359–E386.
  9. Moleti M, Sturniolo G, Di Mauro M, et al. Female Reproductive Factors and Differentiated Thyroid Cancer. Front Endocrinol (Lausanne). 2017; 8: 111.
  10. Derwahl M, Nicula D. Estrogen and its role in thyroid cancer. Endocr Relat Cancer. 2014; 21(5): T273–T283.
  11. Bayram C, Valenti L, Britt H. General practice encounters with men. Aust Fam Physician. 2016; 45(4): 171–174.
  12. Cordina-Duverger E, Leux C, Neri M, et al. Hormonal and reproductive risk factors of papillary thyroid cancer: A population-based case-control study in France. Cancer Epidemiol. 2017; 48: 78–84.
  13. Zamora-Ros R, Rinaldi S, Biessy C, et al. Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: the EPIC study. Int J Cancer. 2015; 136(5): 1218–1227.
  14. Xhaard C, Rubino C, Cléro E, et al. Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study. Am J Epidemiol. 2014; 180(10): 1007–1017.
  15. Manole D, Schildknecht B, Gosnell B, et al. Estrogen promotes growth of human thyroid tumor cells by different molecular mechanisms. J Clin Endocrinol Metab. 2001; 86(3): 1072–1077.
  16. Rajoria S, Suriano R, Shanmugam A, et al. Metastatic phenotype is regulated by estrogen in thyroid cells. Thyroid. 2010; 20(1): 33–41.
  17. Xu S, Chen G, Peng W, et al. Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules? J Endocrinol. 2013; 218(1): 125–133.
  18. Zane M, Parello C, Pennelli G, et al. Estrogen and thyroid cancer is a stem affair: A preliminary study. Biomed Pharmacother. 2017; 85: 399–411.
  19. Luo J, Hendryx M, Manson JE, et al. Hysterectomy, oophorectomy, and risk of thyroid cancer. J Clin Endocrinol Metab. 2016; 101(10): 3812–3819.
  20. Mack WJ, Preston-Martin S, Bernstein L, et al. Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females. Cancer Epidemiol Biomarkers Prev. 1999; 8(11): 991–997.
  21. Wu JM, Wechter ME, Geller EJ, et al. Hysterectomy rates in the United States, 2003. Obstet Gynecol. 2007; 110(5): 1091–1095.
  22. Tamhane N, Imudia AN, Mikhail E. Contemporary management of adnexa at the time of benign hysterectomy: a review of the literature. J Obstet Gynaecol. 2019; 39(7): 896–902.
  23. Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, et al. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2000; 85(2): 645–651.
  24. Xiangying Hu, Lili H, Yifu S. The effect of hysterectomy on ovarian blood supply and endocrine function. Climacteric. 2006; 9(4): 283–289.
  25. Farquhar CM, Sadler L, Harvey SA, et al. The association of hysterectomy and menopause: a prospective cohort study. BJOG. 2005; 112(7): 956–962.
  26. Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021; 372: n160.
  27. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017; 358: j4008.
  28. Parmar M, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in Medicine. 1998; 17(24): 2815–2834, doi: 10.1002/(sici)1097-0258(19981230)17:24<2815::aid-sim110>3.0.co;2-8.
  29. Hoaglin DC. Misunderstandings about Q and 'Cochran's Q test' in meta-analysis. Stat Med. 2016; 35(4): 485–495.
  30. Frentzel-Beyme R, Helmert U. Association between malignant tumors of the thyroid gland and exposure to environmental protective and risk factors. Rev Environ Health. 2000; 15(3): 337–358.
  31. Caini S, Gibelli B, Palli D, et al. Menstrual and reproductive history and use of exogenous sex hormones and risk of thyroid cancer among women: a meta-analysis of prospective studies. Cancer Causes Control. 2015; 26(4): 511–518.
  32. Mannathazhathu AS, George PS, Sudhakaran S, et al. Reproductive factors and thyroid cancer risk: meta-analysis. Head Neck. 2019; 41(12): 4199–4208.
  33. Wang P, Lv L, Qi F, et al. Increased risk of papillary thyroid cancer related to hormonal factors in women. Tumour Biol. 2015; 36(7): 5127–5132.
  34. Negri E, Dal Maso L, Ron E, et al. A pooled analysis of case-control studies of thyroid cancer. II. Menstrual and reproductive factors. Cancer Causes Control. 1999; 10(2): 143–155.
  35. Wilson LF, Tuesley KM, Webb PM, et al. Hysterectomy and risk of breast, colorectal, thyroid, and kidney cancer - an Australian data linkage study. Cancer Epidemiol Biomarkers Prev. 2021; 30(5): 904–911.
  36. Kim M, Kim BoH, Lee H, et al. Thyroid cancer after hysterectomy and oophorectomy: a nationwide cohort study. Eur J Endocrinol. 2021; 184(1): 143–151.
  37. Guenego A, Mesrine S, Dartois L, et al. Relation between hysterectomy, oophorectomy and the risk of incident differentiated thyroid cancer: The E3N cohort. Clin Endocrinol (Oxf). 2019; 90(2): 360–368.
  38. Falconer H, Yin Li, Bellocco R, et al. Thyroid cancer after hysterectomy on benign indications: Findings from an observational cohort study in Sweden. Int J Cancer. 2017; 140(8): 1796–1801.
  39. Altman D, Yin Li, Falconer H. Long-term cancer risk after hysterectomy on benign indications: population-based cohort study. Int J Cancer. 2016; 138(11): 2631–2638.
  40. Kabat GC, Kim MY, Wactawski-Wende J, et al. Menstrual and reproductive factors, exogenous hormone use, and risk of thyroid carcinoma in postmenopausal women. Cancer Causes Control. 2012; 23(12): 2031–2040.
  41. Braganza MZ, Berrington de González A, Schonfeld SJ, et al. Benign breast and gynecologic conditions, reproductive and hormonal factors, and risk of thyroid cancer. Cancer Prev Res (Phila). 2014; 7(4): 418–425.
  42. Thun M, Linet MS, Cerhan JR, Haiman CA, Schottenfeld D. Cancer: epidemiology and prevention. Oxford University Press, Oxford 2018.
  43. Lewy-Trenda I. Estrogen and progesterone receptors in neoplastic and non-neoplastic thyroid lesions. Pol J Pathol. 2002; 53(2): 67–72.
  44. Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update. 2005; 11(4): 411–423.
  45. Kim JJ, Kurita T, Bulun SE. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev. 2013; 34(1): 130–162.
  46. Luoto R, Auvinen A, Pukkala E, et al. Hysterectomy and subsequent risk of cancer. Int J Epidemiol. 1997; 26(3): 476–483.
  47. Luoto R, Grenman S, Salonen S, et al. Increased risk of thyroid cancer among women with hysterectomies. Am J Obstet Gynecol. 2003; 188(1): 45–48.
  48. Rossing MA, Voigt LF, Wicklund KG, et al. Reproductive factors and risk of papillary thyroid cancer in women. Am J Epidemiol. 2000; 151(8): 765–772.
  49. Wong EY, Ray R, Gao DL, et al. Reproductive history, occupational exposures, and thyroid cancer risk among women textile workers in Shanghai, China. Int Arch Occup Environ Health. 2006; 79(3): 251–258.
  50. Truong T, Orsi L, Dubourdieu D, et al. Role of goiter and of menstrual and reproductive factors in thyroid cancer: a population-based case-control study in New Caledonia (South Pacific), a very high incidence area. Am J Epidemiol. 2005; 161(11): 1056–1065.
  51. Lundholm C, Forsgren C, Johansson ALV, et al. Hysterectomy on benign indications in Sweden 1987-2003: a nationwide trend analysis. Acta Obstet Gynecol Scand. 2009; 88(1): 52–58.
  52. Bíró J, Eneroth P, Ritzén EM. Effects of hysterectomy and in-vivo treatment with uterine extracts on plasma concentrations of growth hormone, thyrotrophin and thyroid hormones in rats: a kinetic study. J Endocrinol. 1984; 101(3): 243–248.
  53. Patak E, Pinto FM, Story ME, et al. Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus. Biol Reprod. 2005; 72(5): 1125–1133.
  54. Kim MH, Park YeR, Lim DJ, et al. The relationship between thyroid nodules and uterine fibroids. Endocr J. 2010; 57(7): 615–621.