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Cancer Causes & Control
Published in: Cancer Causes & Control 5/2017

01-05-2017 | Original paper

A prospective cohort study of oral contraceptive use and ovarian cancer among women in the United States born from 1947 to 1964

Authors: Amy L. Shafrir, Helena Schock, Elizabeth M. Poole, Kathryn L. Terry, Rulla M. Tamimi, Susan E. Hankinson, Bernard A. Rosner, Shelley S. Tworoger

Published in: Cancer Causes & Control | Issue 5/2017

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Abstract

Purpose

Oral contraceptives (OCs) have been consistently associated with a reduced ovarian cancer risk; however, most previous studies included women in older birth cohorts using high-dose OC formulations. We assessed OC use, including type and dose, and ovarian cancer risk among women born between 1947 and 1964 using more recent formulations.

Methods

We included 110,929 Nurses’ Health Study II participants. Women reported duration of OC use and brands used from age 13 to baseline (1989) and every 2 years thereafter through 2009. We categorized brands by estrogen and progestin type, dose, and potency, and used Cox proportional hazards models, adjusted for age, calendar time, reproductive factors, and body mass index, to assess associations with ovarian cancer.

Results

Over 2,178,679 person-years of follow-up, we confirmed 281 cases. At baseline, 83% of participants reported ever using OCs. Compared to never use, we observed an increased risk of ovarian cancer with ≤6 months of OC use (HR 1.82; 95% CI 1.13–2.93) but a non-significant 57% (95% CI 0.18–1.03) decreased risk with ≥15 years of OC use. The increased risk among short-term users (≤1 year) was restricted to OCs containing mestranol (HR 1.83; 95% CI 1.16–2.88) and first-generation progestin (HR 1.72; 95% CI 1.11–2.65).

Conclusion

The associations between OCs and ovarian cancer observed for this younger birth cohort differ substantially from the results of previous cohort studies, possibly reflecting changes in OC formulations and use patterns over time, although these results could be due to chance. Additional studies should evaluate newer OC formulations and ovarian cancer risk.
Appendix
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Literature
1.
Hunter DJ, Colditz GA, Hankinson SE et al (2010) Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiol Biomark Prev 19:2496–2502CrossRef
2.
Lipnick RJ, Buring JE, Hennekens CH et al (1986) Oral contraceptives and breast cancer. A prospective cohort study. JAMA 255:58–61CrossRefPubMed
3.
Luhn P, Walker J, Schiffman M et al (2013) The role of co-factors in the progression from human papillomavirus infection to cervical cancer. Gynecol Oncol 128:265–270CrossRefPubMed
4.
Roura E, Travier N, Waterboer T et al (2016) Correction: the influence of hormonal factors on the risk of developing cervical cancer and pre-cancer: results from the EPIC cohort. PLoS ONE 11:e0151427CrossRefPubMedPubMedCentral
5.
Beral V, Doll R CH et al (2008) Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 371:303–314CrossRefPubMed
6.
Thorogood M, Villard-Mackintosh L (1993) Combined oral contraceptives: risks and benefits. Br Med Bull 49:124–139CrossRefPubMed
7.
Schreiber CA, Barnhart K (2009) Contraception. In: Strauss JF, Barbieri RL (eds) Yen and Jaffe’s reproductive endocrinology: physiology, pathophysiology, and clinical management, 6th edn. Saunders Elsevier Inc, Philadelphia
8.
Gerstman BB, Gross TP, Kennedy DL, Bennett RC, Tomita DK, Stadel BV (1991) Trends in the content and use of oral contraceptives in the United States, 1964–1988. Am J Public Health 81:90–96CrossRefPubMedPubMedCentral
9.
Lurie G, Wilkens LR, Thompson PJ et al (2008) Combined oral contraceptive use and epithelial ovarian cancer risk: time-related effects. Epidemiology 19:237–243CrossRefPubMed
10.
Moorman PG, Calingaert B, Palmieri RT et al (2008) Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women. Am J Epidemiol 167:1059–1069CrossRefPubMedPubMedCentral
11.
Lurie G, Thompson P, McDuffie KE, Carney ME, Terada KY, Goodman MT (2007) Association of estrogen and progestin potency of oral contraceptives with ovarian carcinoma risk. Obstet Gynecol 109:597–607CrossRefPubMed
12.
Ness RB, Grisso JA, Klapper J et al (2000) Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. Am J Epidemiol 152:233–241CrossRefPubMed
13.
Royar J, Becher H, Chang-Claude J (2001) Low-dose oral contraceptives: protective effect on ovarian cancer risk. Int J Cancer 95:370–374CrossRefPubMed
14.
Faber MT, Jensen A, Frederiksen K et al (2013) Oral contraceptive use and impact of cumulative intake of estrogen and progestin on risk of ovarian cancer. Cancer Causes Control 24:2197–2206CrossRefPubMed
15.
Kumle M, Weiderpass E, Braaten T et al (2004) Risk for invasive and borderline epithelial ovarian neoplasias following use of hormonal contraceptives: the Norwegian-Swedish Women’s Lifestyle and Health Cohort Study. Br J Cancer 90:1386–1391CrossRefPubMedPubMedCentral
16.
Hunter DJ, Manson JE, Colditz GA et al (1997) Reproducibility of oral contraceptive histories and validity of hormone composition reported in a cohort of US women. Contraception 56:373–378CrossRefPubMed
17.
Dickey RP (1987) Managing contraceptive pill patients, 5th edn. Creative Informatics, Durant
18.
Dickey RP (2002) Managing contraceptive pill patients, 11th edn. EMIS, Inc, Dallas
19.
Dickey RP (2010) Managing contraceptive pill/drug patients, 14th edn. EMIS, Inc, New Orleans
20.
PDR (1974) Physicians’ Desk Reference, 28th edn. Medical Economics Co., Oradell
21.
ADI (1974) American Drug Index. Lippincott, Philadelphia
22.
Althuis MD, Brogan DR, Coates RJ et al (2003) Hormonal content and potency of oral contraceptives and breast cancer risk among young women. Br J Cancer 88:50–57CrossRefPubMedPubMedCentral
23.
Lebovic DI, Gordon JD, Taylor RN (2005) Reproductive endocrinology & infertility: handbook for clinicians, 1st edn. Scrub Hill Press, Inc, Arlington
24.
Opler LA (2005) The complete pill guide: the latest information about generic and brand-name prescription drugs, 2nd edn. Barnes & Noble Publishing, Inc, New York
25.
Davtyan C (2012) Four generations of progestins in oral contraceptives. Proceedings of UCLA Healthcare. UCLA Department of Medicine.
26.
Stampfer MJ, Willett WC, Speizer FE et al (1984) Test of the National Death Index. Am J Epidemiol 119:837–839CrossRefPubMed
27.
Wang M, Spiegelman D, Kuchiba A et al (2016) Statistical methods for studying disease subtype heterogeneity. Stat Med 35:782–800CrossRefPubMed
28.
29.
30.
Rivera R, Yacobson I, Grimes D (1999) The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am J Obstet Gynecol 181:1263–1269CrossRefPubMed
31.
Goldzieher JW (1993) The history of steroidal contraceptive development: the estrogens. Perspect Biol Med 36:363–368CrossRefPubMed
32.
Risch HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 90:1774–1786CrossRefPubMed
33.
Fleming JS, Beaugie CR, Haviv I, Chenevix-Trench G, Tan OL (2006) Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol Cell Endocrinol 247:4–21CrossRefPubMed
34.
Siskind V, Green A, Bain C, Purdie D (2000) Beyond ovulation: oral contraceptives and epithelial ovarian cancer. Epidemiology 11:106–110CrossRefPubMed
35.
Tung KH, Wilkens LR, Wu AH et al (2005) Effect of anovulation factors on pre- and postmenopausal ovarian cancer risk: revisiting the incessant ovulation hypothesis. Am J Epidemiol 161:321–329CrossRefPubMed
36.
Risch HA, Weiss NS, Lyon JL, Daling JR, Liff JM (1983) Events of reproductive life and the incidence of epithelial ovarian cancer. Am J Epidemiol 117:128–139CrossRefPubMed
37.
Braem MG, Onland-Moret NC, van den Brandt PA et al (2010) Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study. Am J Epidemiol 172:1181–1189CrossRefPubMedPubMedCentral
38.
Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE (2007) Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol 166:894–901CrossRefPubMed
39.
Tsilidis KK, Allen NE, Key TJ et al (2011) Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer 105:1436–1442CrossRefPubMedPubMedCentral
40.
Pike MC, Pearce CL, Peters R, Cozen W, Wan P, Wu AH (2004) Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study. Fertil Steril 82:186–195CrossRefPubMed
41.
Cook LS, Pestak CR, Leung ACY et al (2017) Combined oral contraceptive use before the first birth and epithelial ovarian cancer risk. Br J Cancer 116:265–269CrossRefPubMed
42.
Chiaffraino F, Pelucchi C, Parazzini F et al (2001) Reproductive and hormonal factors and ovarian cancer. Ann Oncol 12:337–341CrossRef
43.
44.
Greer JB, Modugno F, Allen GO, Ness RB (2005) Androgenic progestins in oral contraceptives and the risk of epithelial ovarian cancer. Obstet Gynecol 105:731–740CrossRefPubMed
45.
Koushik A, Grundy A, Abrahamowicz M, Arseneau J, Gilbert L, Gotlieb WH, Lacaille J, Mes-Masson AM, Parent MÉ, Provencher DM, Richardson L, Siemiatycki J (2017) Hormonal and reproductive factors and the risk of ovarian cancer. Cancer Causes Control. doi:10.​1007/​s10552-016-0848-9
46.
Bethea TN, Palmer JR, Adams-Campbell LL, Rosenberg L (2016) A prospective study of reproductive factors and exogenous hormone use in relation to ovarian cancer risk among Black women. Cancer Causes Control. doi:10.​1007/​s10552-016-0840-4
47.
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 335:651CrossRefPubMedPubMedCentral
48.
Rosenberg MJ, Waugh MS (1998) Oral contraceptive discontinuation: a prospective evaluation of frequency and reasons. Am J Obstet Gynecol 179:577–582CrossRefPubMed
49.
Rosenberg MJ, Waugh MS, Meehan TE (1995) Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation. Contraception 51:283–288CrossRefPubMed
50.
Bye PGT, Elstein M (1973) Clinical assessment of a low-oestrogen combined oral contraceptive. BMJ 19:389–392CrossRef
51.
Sanders SA, Graham CA, Bass JL, Bancroft J (2001) A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation. Contraception 64:51–58CrossRefPubMed
52.
Goldzieher JW, Moses LE, Averkin E, Scheel C, Taber BZ (1971) A placebo-controlled double-blind crossover investigation of the side effects attributed to oral contraceptives. Fertil Steril 22:609–623CrossRefPubMed
53.
Dionne P, Vickerson F (1974) A double-blind comparison of two oral contraceptives containing 50 mu g. and 30 mu g. ethinyl estradiol. Curr Ther Res Clin Exp 16: 281–288PubMed
54.
Schmider J, Greenblatt DJ, von Moltke LL et al (1997) Biotransformation of mestranol to ethinyl estradiol in vitro: the role of cytochrome P-450 2C9 and metabolic inhibitors. J Clin Pharmacol 37:193–200CrossRefPubMed
55.
Goldzieher JW, Stanczyk FZ (2008) Oral contraceptives and individual variability of circulating levels of ethinyl estradiol and progestins. Contraception 78:4–9CrossRefPubMed
56.
Lukanova A, Lundin E, Akhmedkhanov A et al (2003) Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer 104:636–642CrossRefPubMed
57.
Helzlsouer KJ, Alberg AJ, Gordon GB et al (1995) Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA 274:1926–1930CrossRefPubMed
58.
Schock H, Surcel HM, Zeleniuch-Jacquotte A et al (2014) Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer. Endocr Relat Cancer 21:831–844CrossRefPubMedPubMedCentral
Metadata
Title
A prospective cohort study of oral contraceptive use and ovarian cancer among women in the United States born from 1947 to 1964
Authors
Amy L. Shafrir
Helena Schock
Elizabeth M. Poole
Kathryn L. Terry
Rulla M. Tamimi
Susan E. Hankinson
Bernard A. Rosner
Shelley S. Tworoger
Publication date
01-05-2017
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 5/2017
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-017-0876-0

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