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Bottom Line Summary

Risk of Breast Cancer after Stopping Combination Hormonal Therapy

The Risk of Invasive Breast Cancer Persists after Stopping Combination Hormonal Therapy

Results from the extension phase of the Women's Health Initiative Trials

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The Bottom Line:

  • Women receiving combination hormone therapy with conjugated equine estrogen plus medroxyprogesterone acetate may have increased risk of invasive breast cancer which persists after stopping therapy, but have no increased risk of coronary heart disease.
  • Women without a uterus receiving conjugated equine estrogen alone have a lower risk of invasive breast cancer and no change in their risk for coronary heart disease during or after the intervention.
  • The increased risk of stroke seen in women in both the combination and estrogen alone groups during the intervention phase does not persist at the end of the cumulative follow-up period.

Tips for Discussion with Patients:

  • This is an extension study, results may have been affected by unmeasured variables.
  • Risk of invasive breast cancer persists over time for combination therapy with estrogen and progesterone.
  • Participants in this study received conjugated equine estrogen 0.625 mg/day and medroxyprogesterone acetate 2.5 mg/day. Therefore, the results are applicable to these specific products at these specific doses. This study did not consider lower dose hormone therapy options or estrogen products other than conjugated equine estrogen.


1. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the women’s health initiative randomized trials. JAMA. 2013; 310(13):1353-1368

Written by the Evidence-Based Medicine Task Force

  1. M.E. Beth Smith, DO
  2. KoKo Aung, MD, MPH
  3. Zackary Berger, MD, PhD
  4. Rebecca Beyth, MD, MSc
  5. Daniel Elliott, MD, MSCE
  6. Scott Kaatz, DO, MSc
  7. Deborah Korenstein, MD
  8. Jeremy Sussman, MD, MSc
  9. Daniella Zipkin, MD