Estrogen Alone vs. Estrogen Plus Progestin: What 20 Years of WHI Data Show About Breast Cancer
Menopause & HormonesArticleThe headlines from the Women's Health Initiative linked hormone therapy to breast cancer, but the two trials pointed in opposite directions. After 20 years of follow-up, estrogen alone in women without a uterus was linked to fewer breast cancers and fewer breast cancer deaths, while estrogen plus a progestin was linked to more breast cancers.
In this article
The Women’s Health Initiative (WHI) ran two hormone therapy trials in women aged 50 to 79.1 They’re often lumped together, but on breast cancer they found opposite results.
The two trials
- Estrogen plus progestin (conjugated equine estrogen with medroxyprogesterone acetate) in about 16,600 women with a uterus. Stopped in 2002 after a median of 5.6 years.1
- Estrogen alone (conjugated equine estrogen) in about 10,700 women who’d had a hysterectomy. Stopped in 2004 after a median of 7.2 years.1
What 20 years of follow-up showed
| Estrogen alone | Estrogen + progestin | |
|---|---|---|
| Breast cancer diagnoses vs. placebo | 22% lower | 28% higher |
| Yearly rate, hormone vs. placebo | 0.30% vs. 0.37% | 0.45% vs. 0.36% |
| Breast cancer deaths vs. placebo | 40% lower | No significant difference |
In absolute terms, the yearly differences are small: under one-tenth of a percentage point either way.1
What the WHI says about using hormones today
A 2024 review of all the WHI trials concluded that hormone therapy shouldn’t be used to prevent heart disease, dementia or other chronic diseases, but is effective for moderate to severe hot flashes and other menopause symptoms.2 It supports starting before age 60 for women with bothersome symptoms and no reasons to avoid hormones.2
What this means for you
- The type of hormone matters. Women without a uterus usually take estrogen alone; women with a uterus need a progestogen to protect the uterine lining.
- These trials tested specific pills. Ask whether results apply to patches, gels or other progestogens. Our guide to pill vs. patch clot risk covers one difference.
- Keep up with breast screening. See our hormone therapy and breast screening checklist and dense breast guide.
Our article on whether hormone therapy is safe covers the broader picture, including recent label changes.
Try: “I had a hysterectomy and my hot flashes are severe. Given the WHI estrogen-alone results, is estrogen a reasonable option for me?”
My Body Changed. Now What? includes a Visit Brief. Use it to note whether you have a uterus, your family history and your symptoms before discussing hormone options. See the book.
This article is for general educational purposes only and is not medical advice. It isn't a substitute for diagnosis or treatment from a qualified healthcare professional who knows your health history. Please don't start, stop or switch hormone therapy without talking to your prescriber. If you have a uterus, taking estrogen without a progestogen raises the risk of uterine cancer unless your clinician advises otherwise. A breast lump, nipple changes or bleeding after menopause should be checked promptly. If you think you may be having a medical emergency, call 911 or your local emergency number right away. This article discusses published research. Girl Playbook does not endorse any specific product, test, or provider.
Girl Playbook sells this book. It provides education and worksheets, not individualized medical care.
Sources
The research behind this article, in the order it’s cited. How we source our articles.
- JAMA (full text via PubMed Central), 2020Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women's Health Initiative Randomized Clinical Trials (opens in a new tab)abcde
- JAMA (abstract via PubMed), 2024The Women's Health Initiative Randomized Trials and Clinical Practice: A Review (opens in a new tab)ab
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