Hormone Replacement Therapy

At a Glance

Hormone replacement therapy (HRT) often includes a combination of estrogen and progestin, prescribed to treat menopausal symptoms in women. HRT is a known carcinogen recognized by the International Agency for Research on Cancer (IARC) that has been associated with an increased risk of breast cancer, heart disease, stroke and blood clots.

What is hormone replacement therapy?

HRT is generally prescribed for menopause symptoms. Most formulations include both estrogen and progestin. Estrogen-only HRT can be prescribed, but only for women who have previously undergone surgical hysterectomies.

Where is hormone replacement therapy found?

HRT is a pharmaceutical.

What evidence links hormone replacement therapy to breast cancer?

Several studies have found an increased risk of breast cancer in people using HRT.

  • The Women’s Health Initiative (WHI) was a clinical trial and observational study designed to explore the benefits and risks of combined estrogen-progestin HRT in post-menopausal women. In 2002, the project was halted prior to the end of the study, because researchers observed a significant increase in the relative risk of breast cancer. [1],[2]
  • Analyses of a second arm of the WHI study clarified that the increased risk of breast cancer detected in the study occurred in women taking the combined estrogen-progestin formula, while a decreased risk for breast cancer was found among women taking estrogen-only HRT supplements.[3],[4] It is critical to note that the estrogen-only option can only be offered to women who have previously undergone surgical hysterectomies, because estrogen alone increases the risk of uterine cancer.
  • Swedish researchers halted a five-year study in 2003 after only two years because women with a history of breast cancer taking the combined estrogen-progestin HRT had a significant increase in new tumors compared to women who received other treatments for menopausal symptoms.[5]
  • In 2003, researchers in the Million Women Study (MWS) in the United Kingdom reported the then-current use of all types of post-menopausal HRT significantly increased the risk of breast cancer.[6],[7] Again, the risk was greatest among users of estrogen-progestin combination therapy.
  • Through a California statewide registry and California Health Interview Survey of almost 3 million women, researchers confirmed that combined HRT increases the risk of breast cancer in post-menopausal women, and that stopping use of the combination pill leads to decreased risk of developing breast cancer. Decreased incidence in breast cancer was highest (22.6%) in groups with the greatest decline in using HRT, reducing to 13.9% in moderate HRT use, and smallest (8.8%) with least decline in HRT use.[8]

Who is most likely to be exposed to hormone replacement therapy?

Women who are experiencing menopausal symptoms and have been prescribed HRT by their physician.

Who is most vulnerable to health effects of hormone replacement therapy?

A study examining the possible interactions between use of HRT and race, weight and breast density found that HRT use increased risk for breast cancer in White, Asian and Hispanic women, but not Black women. It is important to note there was no interaction between HRT use and either body mass index or breast density.[9]

What are the top tips to avoid exposure?

Limit use. The IARC advises that, if possible, you should avoid or limit the use of hormone replacement therapy. If HRT is started, the treatment should be taken for the shortest time and at the lowest dose possible to control the symptoms of menopause. The precise therapy should be discussed with the physician before starting treatment.[10]

[1] Writing Group for the Women’s Health Initiative Investigators (2002). Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial. J Am Med Assoc, 288(3):321-333. doi:10.1001/jama.288.3.321.

[2] Rossouw, J., Anderson, G., Prentice, R., LaCroix, A., Kooperberg, C., Stefanick, M., … Ockene, J. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women. J Am Med Assoc, 288, 321–333.

[3] Anderson, G., Limacher, M., Assaf, A., Bassford, T., Beresford, S., Black, H., … Wasserthell-Smoller, S. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled study. J Am Med Assoc, 291, 1701–1712.

[4] Anderson, G.L., Chlebowski, R. T., Aragaki, A.K., Kuller, L.H., Manson, J.E., Gass, M., … Wactawski-Wende, J. (2012). Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol, 13(5), 476–486.

[5] Holmberg, L., & Anderson, H. (2004). HABITS (hormonal replacement therapy after breast cancer—is it safe?) trial stopped. Lancet, 363, 453–455.

[6] Beral, V. (2003). Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet, 362(9382), 419–427.

[7] Anderson, G.L., Chlebowski, R.T., Aragaki, A.K., Kuller, L.H., Manson, J.E., Gass, M., … Wactawski-Wende, J. (2012). Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol, 13(5), 476–486.

[8] Robbins, A., & Clarke, C. (2007). Regional changes in hormone therapy use and breast cancer incidence in California from 2001 to 2004. J Clin Oncol, 25, 3437–3439.

[9] Hou, N. (2013). Hormone Replacement Therapy and Breast Cancer: Hererogeneous Risks by Race, Weight, and Breast Density. Oxford Journals, 105 (18).

[10] IARC: International Agency for Research on Cancer (2016). European Code Against Cancer: 12 Ways to Reduce Your Cancer Risk. http://cancer-code-europe.iarc.fr/index.php/en/ecac-12-ways/pharmaceutical-drugs/questions/68-hormone-replacement-therapy. (Retrieved August 31, 2016.

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