Cancer Causes & Control

, Volume 27, Issue 2, pp 249–258 | Cite as

Use of exogenous hormones and the risk of breast cancer: results from self-reported survey data with validity assessment

  • Sanna HeikkinenEmail author
  • Markku Koskenvuo
  • Nea Malila
  • Tytti Sarkeala
  • Eero Pukkala
  • Janne Pitkäniemi
Original paper



Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data.


The survey ‘Women’s Health and Use of Hormones’ was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys.


We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10–1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (≥2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12–1.68) for premenopausal and 1.11 (95 % CI 1.03–1.20) for postmenopausal women, when compared to never-users of other HC.


Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant.


Hormonal contraceptives Intrauterine device Case–control study Breast cancer Epidemiology 



The original research and data collection for WHH were funded by the German FED Berlin, Center for Epidemiology and Health Research, and it produced a study ‘Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer’ by Dinger, Bardenheuer, and Do Minh, published in 2010. Sanna Heikkinen was supported by the Cancer Society of Finland for the present study (Epidemiological Researcher-grant,

Contribution statement

SH and JP made data analysis and wrote the manuscript. MK and EP designed the WHH study and related data collection. NM, TS, EP, and MK critically commented the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10552_2015_702_MOESM1_ESM.docx (36 kb)
Supplementary material 1 (DOCX 37 kb)


  1. 1.
    Mean annual numbers of new cancer cases in 1966–2012, by primary site and period, FEMALES. Finnish Cancer Registry, Cancer Statistics 2014. Accessed 15 Dec 2014
  2. 2.
    Engholm G, Ferlay J, Christensen N, Johannesen TB, Khan S, Køtlum JE et al (2013) NORDCAN: cancer incidence, mortality, prevalence and survival in the nordic countries, version 6.0 (4 Dec 2013). Accessed 4 Dec 2014
  3. 3.
    Health Care Act (2010) Sect 339/2011 Government decree on screenings, 1326/2010. Accessed 10 Dec 2014
  4. 4.
    Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 358(9291):1389–1399CrossRefGoogle Scholar
  5. 5.
    Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K et al (2005) Benign breast disease and the risk of breast cancer. N Engl J Med 353(3):229–237PubMedCrossRefGoogle Scholar
  6. 6.
    McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 15(6):1159–1169CrossRefGoogle Scholar
  7. 7.
    Folkerd E, Dowsett M (2013) Sex hormones and breast cancer risk and prognosis. Breast 22:S38–S43PubMedCrossRefGoogle Scholar
  8. 8.
    Collaborative Group on Hormonal Factors in Breast Cancer (2012) Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 13(11):1141–1151PubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kobayashi S, Sugiura H, Ando Y, Shiraki N, Yanagi T, Yamashita H et al (2012) Reproductive history and breast cancer risk. Breast Cancer 19(4):302–308PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Anderson KN, Schwab RB, Martinez ME (2014) Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast Cancer Res Treat 144(1):1–10PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    National Cancer Institute: PDQ® Breast Cancer Prevention. Bethesda, MD: National Cancer Institute. 2014. Date last modified: 5 Dec 2014. Accessed 16 Dec 2014
  12. 12.
    Hunter DJ, Colditz GA, Hankinson SE, Malspeis S, Spiegelman D, Chen W et al (2010) Oral contraceptive use and breast cancer: a prospective study of young women. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 19(10):2496–2502CrossRefGoogle Scholar
  13. 13.
    Rosenberg L, Zhang Y, Coogan PF, Strom BL, Palmer JR (2009) A case–control study of oral contraceptive use and incident breast cancer. Am J Epidemiol 169(4):473–479PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Marchbanks PA, Curtis KM, Mandel MG, Wilson HG, Jeng G, Folger SG et al (2012) Oral contraceptive formulation and risk of breast cancer. Contraception 85(4):342–350PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Lyytinen HK, Dyba T, Ylikorkala O, Pukkala EI (2010) A case–control study on hormone therapy as a risk factor for breast cancer in Finland: intrauterine system carries a risk as well. Int J Cancer J Int Cancer 126(2):483–489CrossRefGoogle Scholar
  16. 16.
    Soini T, Hurskainen R, Grénman S, Mäenpää J, Paavonen J, Pukkala E (2014) Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland. Obstet Gynecol 124(2 Pt 1):292–299PubMedCrossRefGoogle Scholar
  17. 17.
    Dinger J, Bardenheuer K, Minh TD (2011) Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer. Contraception 83(3):211–217PubMedCrossRefGoogle Scholar
  18. 18.
    Backman T, Rauramo I, Jaakkola K, Inki P, Vaahtera K, Launonen A et al (2005) Use of the levonorgestrel-releasing intrauterine system and breast cancer. Obstet Gynecol 106(4):813–817PubMedCrossRefGoogle Scholar
  19. 19.
    Beral V, Million Women Study Collaborators (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet Lond Engl 362(9382):419–427CrossRefGoogle Scholar
  20. 20.
    Hou N, Hong S, Wang W, Olopade OI, Dignam JJ, Huo D (2013) Hormone replacement therapy and breast cancer: heterogeneous risks by race, weight, and breast density. J Natl Cancer Inst 105(18):1365–1372PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Lee SA, Ross RK, Pike MC (2005) An overview of menopausal oestrogen-progestin hormone therapy and breast cancer risk. Br J Cancer 92(11):2049–2058PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Collins JA, Blake JM, Crosignani PG (2005) Breast cancer risk with postmenopausal hormonal treatment. Hum Reprod Update 11(6):545–560PubMedCrossRefGoogle Scholar
  23. 23.
    Rothman KJ, Greenland S, Lash TR (2008) Modern epidemiology, 3rd edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  24. 24.
    Peytcheva E, Groves RM (2009) Using variation in response rates of demographic subgroups as evidence of nonresponse bias in survey estimates. J Off Stat 25(2):193–201Google Scholar
  25. 25.
    Etter JF, Perneger TV (1997) Analysis of non-response bias in a mailed health survey. J Clin Epidemiol 50(10):1123–1128PubMedCrossRefGoogle Scholar
  26. 26.
    Groves RM, Peytcheva E (2008) The impact of nonresponse rates on nonresponse bias: a meta-analysis. Public Opin Q 72:167–189CrossRefGoogle Scholar
  27. 27.
    Teppo L, Pukkala E, Lehtonen M (1994) Data quality and quality control of a population-based cancer registry. Experience in Finland. Acta Oncol Stockh Swed 33(4):365–369CrossRefGoogle Scholar
  28. 28.
    Health Behaviour and Health among the Finnish Adult Population, Spring 2010 (AVTK). Report 15/2011. National Institute for Health and Welfare (THL). Accessed 21 Nov 2014
  29. 29.
    National FINRISK Study 2007. KTL-National Public Health Institute, Finland. 2008. Accessed 21 Oct 2014
  30. 30.
    Official Statistics of Finland (OSF): Educational structure of population. Statistics Finland. Report no.: ISSN = 1799-4586. Accessed 21 Oct 2014
  31. 31.
    Nelson HD, Zakher B, Cantor A, Fu R, Griffin J, O’Meara ES et al (2012) Risk factors for breast cancer for women aged 40 to 49 years: a systematic review and meta-analysis. Ann Intern Med 156(9):635–648PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Hamajima N, Hirose K, Tajima K, Rohan T, Calle EE, Heath CW Jr et al (2002) Alcohol, tobacco and breast cancer–collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87(11):1234–1245PubMedCrossRefGoogle Scholar
  33. 33.
    Reeves Gk, Pirie K, Green J, Bull D, Beral V, Million Women Study Collaborators (2012) Comparison of the effects of genetic and environmental risk factors on in situ and invasive ductal breast cancer. Int J Cancer J Int Cancer 131(4):930–937CrossRefGoogle Scholar
  34. 34.
    Li H, Beeghly-Fadiel A, Wen W, Lu W, Gao YT, Xiang YB et al (2013) Gene-environment interactions for breast cancer risk among Chinese women: a report from the Shanghai Breast Cancer Genetics Study. Am J Epidemiol 177(2):161–170PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Ghiasvand R, Maram ES, Tahmasebi S, Tabatabaee SHR (2011) Risk factors for breast cancer among young women in southern Iran. Int J Cancer 129(6):1443–1449PubMedCrossRefGoogle Scholar
  36. 36.
    Kotsopoulos J, Chen WY, Gates MA, Tworoger SS, Hankinson SE, Rosner BA (2010) Risk factors for ductal and lobular breast cancer: results from the nurses’ health study. Breast Cancer Res 12(6):R106PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Lyytinen HK, Dyba T, Ylikorkala O, Pukkala EI (2010) A case–control study on hormone therapy as a risk factor for breast cancer in Finland: intrauterine system carries a risk as well. Int J Cancer J Int Cancer 126(2):483–489CrossRefGoogle Scholar
  38. 38.
    Gierisch JM, Coeytaux RR, Urrutia RP, Havrilesky LJ, Moorman PG, Lowery WJ et al (2013) Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 22(11):1931–1943CrossRefGoogle Scholar
  39. 39.
    Beaber EF, Buist DSM, Barlow WE, Malone KE, Reed SD, Li CI (2014) Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age. Cancer Res 74(15):4078–4089PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Vessey M, Yeates D (2013) Oral contraceptive use and cancer: final report from the Oxford-Family Planning Association contraceptive study. Contraception 88(6):678–683PubMedCrossRefGoogle Scholar
  41. 41.
    Braaten T, Weiderpass E, Kumle M, Adami H-O, Lund E (2004) Education and risk of breast cancer in the Norwegian-Swedish women’s lifestyle and health cohort study. Int J Cancer 110(4):579–583PubMedCrossRefGoogle Scholar
  42. 42.
    Soini T, Hurskainen R, Grénman S, Mäenpää J, Paavonen J, Joensuu H et al (2015) Levonorgestrel-releasing intrauterine system and the risk of breast cancer: a nationwide cohort study. Acta Oncol Stockh Swed 4:1–5Google Scholar
  43. 43.
    Marchbanks PA, McDonald JA, Wilson HG, Folger SG, Mandel MG, Daling JR et al (2002) Oral contraceptives and the risk of breast cancer. N Engl J Med 346(26):2025–2032PubMedCrossRefGoogle Scholar
  44. 44.
    Official Statistics Finland (OSF): Population structure 2009. Statistics Finland. 2009. Accessed 12 Dec 2014
  45. 45.
    European Health Risk Monitoring Project (2002) Recommendation for indicators, international collaboration, protocol and manual of operations for chronic disease risk factor surveys. [Internet]. [cited 2015 Mar 25].
  46. 46.
    Strandhagen E, Berg C, Lissner L, Nunez L, Rosengren A, Torén K et al (2010) Selection bias in a population survey with registry linkage: potential effect on socioeconomic gradient in cardiovascular risk. Eur J Epidemiol 25(3):163–172PubMedCrossRefGoogle Scholar
  47. 47.
    Groves RM, Presser S, Dipko S (2004) The role of topic interest in survey participation decisions. Public Opin Q 68(1):2–31CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Finnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer ResearchHelsinkiFinland
  2. 2.Department of Public Health, Hjelt InstituteUniversity of HelsinkiHelsinkiFinland
  3. 3.School of Health SciencesUniversity of TampereTampereFinland

Personalised recommendations