Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis
The purpose of this meta-analysis was to determine the strength of the association between gynecologic surgeries, tubal ligation and hysterectomy, and ovarian cancer.
We searched the PubMed, Web of Science, and Embase databases for all English-language articles dated between 1969 through March 2011 using the keywords “ovarian cancer” and “tubal ligation” or “tubal sterilization” or “hysterectomy.” We identified 30 studies on tubal ligation and 24 studies on hysterectomy that provided relative risks for ovarian cancer and a p-value or 95% confidence interval (CI) to include in the meta-analysis. Summary RRs and 95% CIs were calculated using a random-effects model.
The summary RR for women with vs. without tubal ligation was 0.70 (95%CI: 0.64, 0.75). Similarly, the summary RR for women with vs. without hysterectomy was 0.74 (95%CI: 0.65, 0.84). Simple hysterectomy and hysterectomy with unilateral oophorectomy were associated with a similar decrease in risk (summery RR = 0.62, 95%CI: 0.49-0.79 and 0.60, 95%CI: 0.47-0.78, respectively). In secondary analyses, the association between tubal ligation and ovarian cancer risk was stronger for endometrioid tumors (summary RR = 0.45, 95%CI: 0.33, 0.61) compared to serous tumors.
Observational epidemiologic evidence strongly supports that tubal ligation and hysterectomy are associated with a decrease in the risk of ovarian cancer, by approximately 26-30%. Additional research is needed to determine whether the association between tubal ligation and hysterectomy on ovarian cancer risk differs by individual, surgical, and tumor characteristics.
- Society AC: Cancer facts & Figures 2008. , ; 2008. In
- Moorman PG, Schildkraut JM, Calingaert B, Halabi S, Vine MF, Berchuck A: Ovulation and ovarian cancer: a comparison of two methods for calculating lifetime ovulatory cycles (United States). Cancer Causes Control 2002,13(9):807–811. CrossRef
- Lukanova A, Kaaks R: Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev 2005,14(1):98–107.
- Cramer DW, Titus-Ernstoff L, McKolanis JR, Welch WR, Vitonis AF, Berkowitz RS, Finn OJ: Conditions associated with antibodies against the tumor-associated antigen MUC1 and their relationship to risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2005,14(5):1125–1131. CrossRef
- DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986,7(3):177–188. CrossRef
- Begg CB, Mazumdar M, Egger M, Davey Smith G, Schneider M, Minder C, DerSimonian R, Laird N, Lau J, Ioannidis JP, Schmid CH: Operating characteristics of a rank correlation test for publication bias Bias in meta-analysis detected by a simple, graphical test Meta-analysis in clinical trials Summing up evidence: one answer is not always enough. Biometrics 1994,50(4):1088–1101. CrossRef
- Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997,315(7109):629–634. CrossRef
- Lau J, Ioannidis JP, Schmid CH: Summing up evidence: one answer is not always enough. Lancet 1998,351(9096):123–127. CrossRef
- Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT: Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol 2004,191(3):733–740. CrossRef
- Jordan SJ, Green AC, Whiteman DC, Moore SP, Bain CJ, Gertig DM, Webb PM: Serous ovarian, fallopian tube and primary peritoneal cancers: a comparative epidemiological analysis. Int J Cancer 2008,122(7):1598–1603. CrossRef
- Ness RB, Dodge RC, Edwards RP, Baker JA, Moysich KB: Contraception methods, beyond oral contraceptives and tubal ligation, and risk of ovarian cancer. Ann Epidemiol ,21(3):188–196.
- Moorman PG, Palmieri RT, Akushevich L, Berchuck A, Schildkraut JM: Ovarian cancer risk factors in African-American and white women. Am J Epidemiol 2009,170(5):598–606. CrossRef
- Antoniou AC, Rookus M, Andrieu N, Brohet R, Chang-Claude J, Peock S, Cook M, Evans DG, Eeles R, Nogues C, Faivre L, Gesta P, van Leeuwen FE, Ausems MG, Osorio A, Caldes T, Simard J, Lubinski J, Gerdes AM, Olah E, Furhauser C, Olsson H, Arver B, Radice P, Easton DF, Goldgar DE: Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev 2009,18(2):601–610. CrossRef
- Dorjgochoo T, Shu XO, Li HL, Qian HZ, Yang G, Cai H, Gao YT, Zheng W: Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a large prospective study, from 1996 to 2006. Int J Cancer 2009,124(10):2442–2449. CrossRef
- Nagle CM, Olsen CM, Webb PM, Jordan SJ, Whiteman DC, Green AC: Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors. Eur J Cancer 2008,44(16):2477–2484. CrossRef
- Jordan SJ, Green AC, Whiteman DC, Webb PM: Risk factors for benign serous and mucinous epithelial ovarian tumors. Obstet Gynecol 2007,109(3):647–654. CrossRef
- Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE: Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol 2007,166(8):894–901. CrossRef
- McLaughlin JR, Risch HA, Lubinski J, Moller P, Ghadirian P, Lynch H, Karlan B, Fishman D, Rosen B, Neuhausen SL, Offit K, Kauff N, Domchek S, Tung N, Friedman E, Foulkes W, Sun P, Narod SA: Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case–control study. Lancet Oncol 2007,8(1):26–34. CrossRef
- Kjaer SK, Mellemkjaer L, Brinton LA, Johansen C, Gridley G, Olsen JH: Tubal sterilization and risk of ovarian, endometrial and cervical cancer. A Danish population-based follow-up study of more than 65 000 sterilized women. Int J Epidemiol 2004,33(3):596–602. CrossRef
- McGuire V, Felberg A, Mills M, Ostrow KL, DiCioccio R, John EM, West DW, Whittemore AS: Relation of contraceptive and reproductive history to ovarian cancer risk in carriers and noncarriers of BRCA1 gene mutations. Am J Epidemiol 2004,160(7):613–618. CrossRef
- Pike MC, Pearce CL, Peters R, Cozen W, Wan P, Wu AH: Hormonal factors and the risk of invasive ovarian cancer: a population-based case–control study. Fertil Steril 2004,82(1):186–195. CrossRef
- Risch HA, Marrett LD, Jain M, Howe GR: Differences in risk factors for epithelial ovarian cancer by histologic type. Results of a case–control study. Am J Epidemiol 1996,144(4):363–372. CrossRef
- Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, Tucker MA, Struewing JP, Hartge P: Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case–control study. J Natl Cancer Inst 2003,95(14):1072–1078. CrossRef
- Wittenberg J, Cook LS, Rossing MA, Weiss NS: Reproductive risk factors for mucinous and non-mucinous epithelial ovarian cancer. Epidemiology 1999,10(6):761–763. CrossRef
- Kreiger N, Sloan M, Cotterchio M, Parsons P: Surgical procedures associated with risk of ovarian cancer. Int J Epidemiol 1997,26(4):710–715. CrossRef
- Green A, Purdie D, Bain C, Siskind V, Russell P, Quinn M, Ward B: Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of Women’s Health Study Group. Int J Cancer 1997,71(6):948–951.
- Cornelison TL, Natarajan N, Piver MS, Mettlin CJ: Tubal ligation and the risk of ovarian carcinoma. Cancer Detect Prev 1997,21(1):1–6.
- Miracle-McMahill HL, Calle EE, Kosinski AS, Rodriguez C, Wingo PA, Thun MJ, Heath CW: Tubal ligation and fatal ovarian cancer in a large prospective cohort study. Am J Epidemiol 1997,145(4):349–357. CrossRef
- Rosenblatt KA, Thomas DB: Reduced risk of ovarian cancer in women with a tubal ligation or hysterectomy. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives. Cancer Epidemiol Biomarkers Prev 1996,5(11):933–935.
- Nandakumar A, Anantha N, Dhar M, Ahuja V, Kumar R, Reddy S, Venugopal T, Rajanna VAT, Srinivas : A case–control investigation on cancer of the ovary in Bangalore, India. Int J Cancer 1995,63(3):361–365. CrossRef
- Whittemore AS, Harris R, Itnyre J: Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case–control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992,136(10):1184–1203.
- Booth M, Beral V, Smith P: Risk factors for ovarian cancer: a case–control study. Br J Cancer 1989,60(4):592–598. CrossRef
- Shu XO, Brinton LA, Gao YT, Yuan JM: Population-based case–control study of ovarian cancer in Shanghai. Cancer Res 1989,49(13):3670–3674.
- Koch M, Jenkins H, Gaedke H: Risk factors of ovarian cancer of epithelial origin: a case control study. Cancer Detect Prev 1988,13(2):131–136.
- Koch M, Starreveld AA, Hill GB, Jenkins H: The effect of tubal ligation on the incidence of epithelial cancer of the ovary. Cancer Detect Prev 1984,7(4):241–245.
- Mori M, Harabuchi I, Miyake H, Casagrande JT, Henderson BE, Ross RK: Reproductive, genetic, and dietary risk factors for ovarian cancer. Am J Epidemiol 1988,128(4):771–777.
- Wu AH, Pearce CL, Tseng CC, Templeman C, Pike MC: Markers of inflammation and risk of ovarian cancer in Los Angeles County. Int J Cancer 2009,124(6):1409–1415. CrossRef
- Annegers JF, Strom H, Decker DG, Dockerty MB, O’Fallon WM: Ovarian cancer: incidence and case–control study. Cancer 1979,43(2):723–729. CrossRef
- Luoto R, Auvinen A, Pukkala E, Hakama M: Hysterectomy and subsequent risk of cancer. Int J Epidemiol 1997,26(3):476–483. CrossRef
- Beard CM, Hartmann LC, Atkinson EJ, O’Brien PC, Malkasian GD, Keeney GL, Melton LJ: The epidemiology of ovarian cancer: a population-based study in Olmsted County, Minnesota, 1935–1991. Ann Epidemiol 2000,10(1):14–23. CrossRef
- Braem MG, Onland-Moret NC, van den Brandt PA, Goldbohm RA, Peeters PH, Kruitwagen RF, Schouten LJ: Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study. Am J Epidemiol ,172(10):1181–1189.
- Chiaffarino F, Parazzini F, Decarli A, Franceschi S, Talamini R, Montella M, La Vecchia C: Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer. Gynecol Oncol 2005,97(2):318–322. CrossRef
- Hankinson SE, Hunter DJ, Colditz GA, Willett WC, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE: Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA 1993,270(23):2813–2818.
- Loft A, Lidegaard O, Tabor A: Incidence of ovarian cancer after hysterectomy: a nationwide controlled follow up. Br J Obstet Gynaecol 1997,104(11):1296–1301. CrossRef
- Parazzini F, Negri E, La Vecchia C, Luchini L, Mezzopane R: Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. Obstet Gynecol 1993,81(3):363–366.
- Risch HA, Marrett LD, Howe GR: Parity, contraception, infertility, and the risk of epithelial ovarian cancer. Am J Epidemiol 1994,140(7):585–597.
- Wynder EL, Dodo H, Barber HR: Epidemiology of cancer of the ovary. Cancer 1969,23(2):352–370. CrossRef
- Irwin KL, Weiss NS, Lee NC, Peterson HB: Tubal sterilization, hysterectomy, and the subsequent occurrence of epithelial ovarian cancer. Am J Epidemiol 1991,134(4):362–369.
- Tung KH, Goodman MT, Wu AH, McDuffie K, Wilkens LR, Kolonel LN, Nomura AM, Terada KY, Carney ME, Sobin LH: Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case–control study. Am J Epidemiol 2003,158(7):629–638. CrossRef
- Cramer DW, Xu H: Epidemiologic evidence for uterine growth factors in the pathogenesis of ovarian cancer. Ann Epidemiol 1995,5(4):310–314. CrossRef
- Hakverdi AU, Taner CE, Erden AC, Satici O: Changes in ovarian function after tubal sterilization. Adv Contracept 1994,10(1):51–56. CrossRef
- Radwanska E, Headley SK, Dmowski P: Evaluation of ovarian function after tubal sterilization. J Reprod Med 1982,27(7):376–384.
- Cattanach J: Oestrogen deficiency after tubal ligation. Lancet 1985,1(8433):847–849. CrossRef
- Garza-Flores J, Vazquez-Estrada L, Reyes A, Valero A, Morales del Olmo A, Alba VM, Bonilla C: Assessment of luteal function after surgical tubal sterilization. Adv Contracept 1991,7(4):371–377. CrossRef
- Wu E, Xiao B, Yan W, Li H, Wu B: Hormonal profile of the menstrual cycle in Chinese women after tubal sterilization. Contraception 1992,45(6):583–593. CrossRef
- Eliassen AH, Colditz GA, Rosner B, Hankinson SE: Tubal sterilization in relation to breast cancer risk. Int J Cancer 2006,118(8):2026–2030. CrossRef
- Pinheiro SP, Hankinson SE, Tworoger SS, Rosner BA, McKolanis JR, Finn OJ, Cramer DW: Anti-MUC1 antibodies and ovarian cancer risk: prospective data from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev ,19(6):1595–1601.
- Nagle CM, Bain CJ, Green AC, Webb PM: The influence of reproductive and hormonal factors on ovarian cancer survival. Int J Gynecol Cancer 2008,18(3):407–413. CrossRef
- Modugno F, Ness RB, Wheeler JE: Reproductive risk factors for epithelial ovarian cancer according to histologic type and invasiveness. Ann Epidemiol 2001,11(8):568–574. CrossRef
- Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Journal of Ovarian Research
- Online Date
- May 2012
- Online ISSN
- BioMed Central
- Additional Links
- Author Affiliations
- 1. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- 2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
- 3. Channing Laboratory, 181 Longwood Ave., 3rd Floor, Boston, MA, 02115, USA