Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older

Acta Oncol. 2014 Jun;53(6):752-8. doi: 10.3109/0284186X.2013.878471. Epub 2014 Jan 24.


Background: Findings on potential interactive effects of oral contraceptives (OCs) and hormone replacement therapy (HRT) on breast cancer risk have been inconsistent. We aimed to use population-based cohort data to determine whether former use of OCs affects breast cancer risk among HRT users, taking into account regimens of HRT, duration and currency of use.

Methods: The cohort consisted of 16 928 Icelandic women who visited the Icelandic Cancer Detection Clinic in 1979-2006 and provided information on use of OCs and HRT when they were 48 years or older. By record linkage to the Icelandic Cancer Registry, all breast cancer diagnosed during follow-up was identified. Using Cox regression, hazard ratios (HRs) for breast cancer according to hormone use were estimated, adjusting for menstrual and reproductive risk factors. Also, interaction analyses were carried out.

Results: Breast cancer risk was significantly increased among ever users of combined estrogen and progestin (EP-HRT) preparations (HR=2.61; 95% CI 2.00-3.41) and not among users of estrogen-only regimens (E-only HRT) (HR=1.13; 95% CI 0.85-1.49). Ever users of both OCs and HRT had higher breast cancer risk than users of only one of the two (HR=2.19; 95% CI 1.67-2.87). After restricting the analysis to EP-HRT and focusing on long-term and current use, there was an indication of a negative interaction with ever OC use (p=0.06); HR=2.87; 95% CI 1.79-4.60 for never OC users and HR=2.24; 95% CI 1.51-3.34 for former OC users.

Conclusion: After taking HRT regimen, duration and currency of use into account, the results of our population-based cohort study do not support the notion that former OC use increases breast cancer risk among HRT users, on the contrary there was an indication of a slightly lower risk in former OC users, restricted to current, long-term EP-HRT users.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / epidemiology*
  • Cohort Studies
  • Contraceptives, Oral, Hormonal / therapeutic use*
  • Estrogen Replacement Therapy / methods
  • Estrogen Replacement Therapy / statistics & numerical data*
  • Estrogens / therapeutic use*
  • Female
  • Humans
  • Iceland / epidemiology
  • Middle Aged
  • Progesterone / therapeutic use*
  • Proportional Hazards Models
  • Reproductive History*
  • Risk Factors
  • Time Factors


  • Contraceptives, Oral, Hormonal
  • Estrogens
  • Progesterone