The influence of reproductive factors on colorectal cancer, including oral contraceptive (OC) use, has been examined, but less research is available on OC use and adenomas.
Participants of the Nurses’ Health Study who had a lower bowel endoscopy between 1986 (when endoscopies were first assessed) and 2008 were included in this study. Multivariable logistic regression models for clustered data were used to estimate odds ratios and 95 % confidence intervals [OR (95 % CIs)].
Among 73,058 participants, 51 % (n = 37,382) reported ever using OCs. Ever OC use was associated with a slight increase in non-advanced adenomas [OR 1.11, 95 % CI (1.02, 1.21)] but not with any other endpoints. Duration of OC use was not associated with adenomas, but longer times since last OC use were associated with increased odds of adenomas [e.g., compared to never use, 15+ years since last use: OR 1.17 (1.07, 1.27)]. Shorter times since last OC use were inversely associated [e.g., ≤4 years since last use: OR 0.74 (0.65, 0.84)].
We observed a modest borderline increase in risk of colorectal adenomas with any prior OC use. Additionally, more recent OC use may decrease risk, while exposure in the distant past may modestly increase risk of adenomas.
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Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29. doi:10.3322/caac.20138
La Vecchia C, Franceschi S (1991) Reproductive factors and colorectal cancer. Cancer Causes Control 2(3):193–200
Bostick RM, Potter JD, Kushi LH, Sellers TA, Steinmetz KA, McKenzie DR, Gapstur SM, Folsom AR (1994) Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States). Cancer Causes Control 5(1):38–52
Campbell PT, Newcomb P, Gallinger S, Cotterchio M, McLaughlin JR (2007) Exogenous hormones and colorectal cancer risk in Canada: associations stratified by clinically defined familial risk of cancer. Cancer Causes Control 18(7):723–733. doi:10.1007/s10552-007-9015-7
Fernandez E, La Vecchia C, D’Avanzo B, Franceschi S, Negri E, Parazzini F (1996) Oral contraceptives, hormone replacement therapy and the risk of colorectal cancer. Br J Cancer 73(11):1431–1435
Fernandez E, La Vecchia C, Franceschi S, Braga C, Talamini R, Negri E, Parazzini F (1998) Oral contraceptive use and risk of colorectal cancer. Epidemiology 9(3):295–300
Furner SE, Davis FG, Nelson RL, Haenszel W (1989) A case-control study of large bowel cancer and hormone exposure in women. Cancer Res 49(17):4936–4940
Hannaford P, Elliott A (2005) Use of exogenous hormones by women and colorectal cancer: evidence from the Royal College of General Practitioners’ Oral Contraception Study. Contraception 71(2):95–98. doi:10.1016/j.contraception.2004.08.003
Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ (2007) Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner’s oral contraception study. BMJ 335(7621):651. doi:10.1136/bmj.39289.649410.55
Kabat GC, Miller AB, Rohan TE (2008) Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women. Int J Cancer 122(3):643–646. doi:10.1002/ijc.23079
Kampman E, Bijl AJ, Kok C, van’t Veer P (1994) Reproductive and hormonal factors in male and female colon cancer. Eur J Cancer Prev 3(4):329–336
Kampman E, Potter JD, Slattery ML, Caan BJ, Edwards S (1997) Hormone replacement therapy, reproductive history, and colon cancer: a multicenter, case-control study in the United States. Cancer Causes Control 8(2):146–158
Levi F, Pasche C, Lucchini F, La Vecchia C (2003) Oral contraceptives and colorectal cancer. Dig Liver Dis 35(2):85–87
Lin J, Zhang SM, Cook NR, Manson JE, Buring JE, Lee IM (2007) Oral contraceptives, reproductive factors, and risk of colorectal cancer among women in a prospective cohort study. Am J Epidemiol 165(7):794–801. doi:10.1093/aje/kwk068
Martinez ME, Grodstein F, Giovannucci E, Colditz GA, Speizer FE, Hennekens C, Rosner B, Willett WC, Stampfer MJ (1997) A prospective study of reproductive factors, oral contraceptive use, and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 6(1):1–5
Nichols HB, Trentham-Dietz A, Hampton JM, Newcomb PA (2005) Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin. Cancer Epidemiol Biomarkers Prev 14(5):1212–1218. doi:10.1158/1055-9965.EPI-04-0845
Potter JD, McMichael AJ (1983) Large bowel cancer in women in relation to reproductive and hormonal factors: a case-control study. J Natl Cancer Inst 71(4):703–709
Talamini R, Franceschi S, Dal Maso L, Negri E, Conti E, Filiberti R, Montella M, Nanni O, La Vecchia C (1998) The influence of reproductive and hormonal factors on the risk of colon and rectal cancer in women. Eur J Cancer 34(7):1070–1076
Troisi R, Schairer C, Chow WH, Schatzkin A, Brinton LA, Fraumeni JF Jr (1997) Reproductive factors, oral contraceptive use, and risk of colorectal cancer. Epidemiology 8(1):75–79
van Wayenburg CA, van der Schouw YT, van Noord PA, Peeters PH (2000) Age at menopause, body mass index, and the risk of colorectal cancer mortality in the Dutch Diagnostisch Onderzoek Mammacarcinoom (DOM) cohort. Epidemiology 11(3):304–308
Vessey M, Painter R, Yeates D (2003) Mortality in relation to oral contraceptive use and cigarette smoking. Lancet 362(9379):185–191. doi:10.1016/S0140-6736(03)13907-4
Wu-Williams AH, Lee M, Whittemore AS, Gallagher RP, Jiao DA, Zheng S, Zhou L, Wang XH, Chen K, Jung D et al (1991) Reproductive factors and colorectal cancer risk among Chinese females. Cancer Res 51(9):2307–2311
Jacobson JS, Neugut AI, Garbowski GC, Ahsan H, Waye JD, Treat MR, Forde KA (1995) Reproductive risk factors for colorectal adenomatous polyps (New York City, NY, United States). Cancer Causes Control 6(6):513–518
Peipins LA, Newman B, Sandler RS (1997) Reproductive history, use of exogenous hormones, and risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 6(9):671–675
Platz EA, Martinez ME, Grodstein F, Fuchs CS, Colditz GA, Stampfer MJ, Giovannucci E (1997) Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States). Cancer Causes Control 8(6):894–903
Grodstein F, Martinez ME, Platz EA, Giovannucci E, Colditz GA, Kautzky M, Fuchs C, Stampfer MJ (1998) Postmenopausal hormone use and risk for colorectal cancer and adenoma. Ann Intern Med 128(9):705–712
Grodstein F, Newcomb PA, Stampfer MJ (1999) Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med 106(5):574–582. doi:10.1016/S0002-9343(99)00063-7
Hebert-Croteau N (1998) A meta-analysis of hormone replacement therapy and colon cancer in women. Cancer Epidemiol Biomarkers Prev 7(8):653–659
Potter JD, Bostick RM, Grandits GA, Fosdick L, Elmer P, Wood J, Grambsch P, Louis TA (1996) Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case-Control Study. Cancer Epidemiol Biomarkers Prev 5(10):779–784
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333
Wolf LA, Terry PD, Potter JD, Bostick RM (2007) Do factors related to endogenous and exogenous estrogens modify the relationship between obesity and risk of colorectal adenomas in women? Cancer Epidemiol Biomarkers Prev 16(4):676–683. doi:10.1158/1055-9965.EPI-06-0883
Woodson K, Lanza E, Tangrea JA, Albert PS, Slattery M, Pinsky J, Caan B, Paskett E, Iber F, Kikendall JW, Lance P, Shike M, Weissfeld J, Schatzkin A (2001) Hormone replacement therapy and colorectal adenoma recurrence among women in the Polyp Prevention Trial. J Natl Cancer Inst 93(23):1799–1805
McMichael AJ, Potter JD (1980) Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. J Natl Cancer Inst 65(6):1201–1207
Lampe JW, Fredstrom SB, Slavin JL, Potter JD (1993) Sex differences in colonic function: a randomised trial. Gut 34(4):531–536
Campagnoli C, Biglia N, Altare F, Lanza MG, Lesca L, Cantamessa C, Peris C, Fiorucci GC, Sismondi P (1993) Differential effects of oral conjugated estrogens and transdermal estradiol on insulin-like growth factor 1, growth hormone and sex hormone binding globulin serum levels. Gynecol Endocrinol 7(4):251–258
Hunter DJ, Colditz GA, Hankinson SE, Malspeis S, Spiegelman D, Chen W, Stampfer MJ, Willett WC (2010) Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiol Biomarkers Prev 19(10):2496–2502. doi:10.1158/1055-9965.EPI-10-0747
Terry MB, Neugut AI, Bostick RM, Sandler RS, Haile RW, Jacobson JS, Fenoglio-Preiser CM, Potter JD (2002) Risk factors for advanced colorectal adenomas: a pooled analysis. Cancer Epidemiol Biomarkers Prev 11(7):622–629
Belanger CF, Hennekens CH, Rosner B, Speizer FE (1978) The nurses’ health study. Am J Nurs 78(6):1039–1040
Rimm EB, Stampfer MJ, Colditz GA, Chute CG, Litin LB, Willett WC (1990) Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1(6):466–473
Therneau TM, Hamilton SA (1997) rhDNase as an example of recurrent event analysis. Stat Med 16(18):2029–2047
Colin EM, Van Den Bemd GJ, Van Aken M, Christakos S, De Jonge HR, Deluca HF, Prahl JM, Birkenhager JC, Buurman CJ, Pols HA, Van Leeuwen JP (1999) Evidence for involvement of 17beta-estradiol in intestinal calcium absorption independent of 1,25-dihydroxyvitamin D3 level in the Rat. J Bone Miner Res 14(1):57–64. doi:10.1359/jbmr.19126.96.36.199
Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7(4):536–540. doi:10.1038/ng0894-536
Lointier P, Wildrick DM, Boman BM (1992) The effects of steroid hormones on a human colon cancer cell line in vitro. Anticancer Res 12(4):1327–1330
Newcomb PA, Pocobelli G, Chia V (2008) Why hormones protect against large bowel cancer: old ideas, new evidence. Adv Exp Med Biol 617:259–269. doi:10.1007/978-0-387-69080-3_24
Oshima CT, Wonraht DR, Catarino RM, Mattos D, Forones NM (1999) Estrogen and progesterone receptors in gastric and colorectal cancer. Hepatogastroenterology 46(30):3155–3158
Schwartz B, Smirnoff P, Shany S, Liel Y (2000) Estrogen controls expression and bioresponse of 1,25-dihydroxyvitamin D receptors in the rat colon. Mol Cell Biochem 203(1–2):87–93
Slattery ML, Ballard-Barbash R, Edwards S, Caan BJ, Potter JD (2003) Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Cancer Causes Control 14(1):75–84
Smirnoff P, Liel Y, Gnainsky J, Shany S, Schwartz B (1999) The protective effect of estrogen against chemically induced murine colon carcinogenesis is associated with decreased CpG island methylation and increased mRNA and protein expression of the colonic vitamin D receptor. Oncol Res 11(6):255–264
Barone M, Tanzi S, Lofano K, Scavo MP, Guido R, Demarinis L, Principi MB, Bucci A, Di Leo A (2008) Estrogens, phytoestrogens and colorectal neoproliferative lesions. Genes Nutr 3(1):7–13. doi:10.1007/s12263-008-0081-6
Piper JM, Kennedy DL (1987) Oral contraceptives in the United States: trends in content and potency. Int J Epidemiol 16(2):215–221
The NHS was supported by research Grants UM1CA186107 and P01CA87969 of the National Institutes of Health. BMC was supported by the Training Programs in Cancer Epidemiology (T32CA09001) from the National Cancer Institute and in Reproductive, Perinatal, and Pediatric Epidemiology (T32HD060454) as well as Grant F32HD084000 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. WW was supported by Entertainment Foundation National Colon Cancer Research Alliance. An abstract of this work was presented at the Association for Cancer Research Annual Meeting on 7 April 2014 and the Society for Epidemiologic Research Annual Conference on 26 June 2014. We would like to thank the participants and staff of the Nurses’ Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. Also, special thanks to Scott Smith for his programming assistance.
Conflict of interest
The authors declare that they have no conflict of interest.
Return of the questionnaires was considered informed consent.
Research involving human participants
The study was approved by the Institutional Review Board of Brigham and Women’s Hospital in Boston.
Kana Wu and Karin B. Michels have contributed equally to this work.
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Charlton, B.M., Giovannucci, E., Fuchs, C.S. et al. A prospective study of oral contraceptive use and colorectal adenomas. Cancer Causes Control 27, 749–757 (2016). https://doi.org/10.1007/s10552-016-0752-3
- Colorectal neoplasms
- Intestinal polyps
- Reproductive history