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Study: Estrogen without progesterone for hormone replacement may lower breast cancer risk


Women with average breast cancer risk who took estrogen without progesterone after menopause had lower rates of breast cancer than those who did not take any hormone replacement. This finding comes from studies looking at the safety of the use of estrogen alone as hormone replacement therapy. (Posted 2/13/24)

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Estrogen without progesterone for hormone replacement may lower breast cancer risk
Glossary on


Most relevant for: Postmenopausal people on hormone replacement therapy.
It may also be relevant for:

  • healthy people with average cancer risk

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

This study combines data from one large and nine small studies to determine how estrogen-only hormone replacement therapy after menopause affects the risk of developing breast cancer.

Why is this study important?

Prior research has shown that plus progesterone hormone therapy after menopause increases the risk of breast cancer.  However, while some studies have shown that taking without progesterone increased the risk of breast cancer, others reported that it decreased breast cancer risk.

This new study looks at the results of multiple past studies; it included only high-quality research known as controlled trials. These types of trials help researchers compare multiple groups of people who received different types of medical care to determine whether their outcomes differed.

The large Women’s Health Initiative (WHI) study compared the outcomes of women who took without progesterone to those who did not did not take any hormone replacement. Participants who took alone were less likely to develop breast cancer and less likely to die of breast cancer than those who did not take any hormone replacement. In contrast, two other large studies found that alone increased a woman’s risk of developing breast cancer.

Study findings

Women who took estrogen-only hormone therapy after menopause have lower rates of breast cancer than those who did not take hormone therapy. These results come from an analysis of 10 control trials. The largest—the Women’s Health Initiative—had the most (10,739) participants. Together, the nine smaller studies included 3,500 participants.

Researchers found that:

  • In the combined 10 studies, women who took were 33% less likely to develop breast cancer than those who did not take hormone therapy.
    • At 10-year follow-up; results from the WHI study showed that alone compared to no hormone therapy decreased breast cancer risk by 37%.
    • Results for the 9 smaller studies were similar to the early results from the Women’s Health Initiative data. Together, the results from these studies showed that participants who took alone had a 35% lower risk of developing breast cancer.
  • Women who started earlier saw a stronger protective effect, according to the data from the WHI.
  • The type of taken (conjugated equine , Estradiol or estrone sulfate) did not affect the study results.

At the time of enrollment, all participants in the Women’s Health Initiative study:

  • were postmenopausal
  • had a hysterectomy
  • had never been previously diagnosed with breast cancer
  • had a normal

The other studies had similar criteria. However, some studies included women with a history of breast cancer, although no conclusions were made about this group.

Participants took for varying amounts of time, ranging from an average of two years in some studies to over seven years in the WHI study. WHI participants were followed for more than 20 years.

What does this mean for me?

If you are postmenopausal, have an average risk for breast cancer and are taking, or thinking of taking estrogen-only hormone replacement, you do not need to worry about it increasing your risk of breast cancer. These results do not recommend to prevent breast cancer. Dr. Pamela Goodwin of the University of Toronto, who commented on these results at the 2023 San Antonio Breast Cancer Symposium, made these points:

  • This study included women who had hysterectomies. Other approved drugs are available for them to prevent breast cancer, some of which may be more effective than estrogen-only hormone replacement.
  • Doctors still do not understand why appears to protect against breast cancer, since blocking can prevent a recurrence.

This study is unlikely to change clinical practice, although it may be reassuring to women who choose to take hormone replacement with alone. Importantly, other risks are associated with estrogen-only hormone replacement therapy, including an increased risk of stroke and blood clots.

For women with a uterus, must be prescribed along with to protect against uterine cancer.

This study did not specifically look at women with inherited mutations linked to breast cancer or women who had early-onset menopause due to risk-reducing surgery. A study by Joanne Kotosopolous and colleagues in 2018 suggest that women with mutations may safely take alone as hormone therapy. However, data is lacking for women with mutations – more research is needed to understand how taking as hormone therapy would impact women with a mutation.

If you are struggling with symptoms of menopause, experts trained in menopause management, such as members of the North American Menopause Society, can help you understand your options.


Chlebowski R, Aragaki A, Pan K, Mortimer J, et al. trials of estrogen-alone and breast cancer incidence: A . Poster Spotlight Session 7: Panel Discussion 1 Moderated by P. Goodwin. 2023 San Antonio Breast Cancer Symposium. Presented by J. Mortimer.

Chlebowski RT, Anderson GL, Aragaki AK, Manson JE, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women's Health Initiative clinical trials. JAMA. 2020 Jul 28;324(4):369-380.

Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant of the worldwide epidemiological evidence. Lancet. 2019 Sep 28;394(10204):1159-1168.

Kotosopolous J, Gronwald J, Karlan BY, et al. Hormone replacement therapy after and breast cancer risk among mutation carriers. JAMA Oncology. 2018;4(8):1059–1065.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 2/13/24

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • What are the risks and benefits of taking ?
  • If I decide to take hormone replacement, is alone an option for me?
  • What do you recommend to help me feel better as I go through menopause?
  • What can I do to decrease my risk of breast cancer?
  • Can you refer me to a menopause expert?

Open clinical trials
Open clinical trials

The following are studies on menopause and menopause management for survivors and previvors:

Updated: 02/03/2024

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Finding experts

The following resources can help you locate an expert near you or via telehealth. 

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Some symptoms of menopause may be managed by other experts. People experiencing menopause symptoms may benefit from a consultation with the following experts.

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  • The National Certification Commission for Acupuncture and Oriental Medicine has a searchable directory of licensed acupuncturists. 

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Updated: 08/18/2023

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