A Provocative Study Shows Taking Estrogen Drops Breast Cancer Mortality

While it has risks, HRT in the form of estrogen alone is associated with lower risk of getting (and dying from) breast cancer.

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The Women’s Health Initiative clinical experiment aimed, among other goals, to better understand the relationship between hormone replacement therapy and breast cancer risk. Now we get news about hormones and mortality. Today, we turn to a surprising new finding.

We begin with a nod to the ever-present and provocative headlines. Hormonal replacement therapy is going to give you breast cancer. Or dementia. On the other side, we hear HRT will make you forever young.

Here is the opinion of physician Robert Wilson, writing in his 1966 bestseller Feminine Forever: “Menopause is an illness, and the cure is hormones, without which women are condemned to witness the death of their own womanhood.”

Continuing, he opined that “I have often been haunted by the thought that except for the tiny stream of estrogen… this woman might have died a violent death at the hands of her own husband.” Perhaps not surprisingly, the author got money from Wyeth, the pharmaceutical maker of the drug he promoted.

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The bad (and some good) of estrogen and progestin in combination

Researchers in the United States created the Women’s Health Initiative in 1991. They aimed to learn more about how to reduce the burdens of diseases such as:

  • heart disease
  • stroke
  • breast cancer
  • colon and rectal cancer
  • significant bone loss (a condition known as osteoporosis, one that can lead to the breaking of bones).

The 15-year study included over 160,000 participants, with an age range of 50 to 79 years. In 2002, the study authors reported several disturbing findings. Post-menopausal women who had taken a combination of estrogen and progestin had a higher risk of heart disease, stroke, breast cancer, blood clots, and urinary control loss.

On the positive side, those who used the combination of the two hormones dropped their chances of breaking bones. They also had a lower risk of getting colorectal cancer. Recognizing the aforementioned increased risk of heart disease, stroke, breast cancer, and more, many women gave up their hormone replacement therapy. There was a steep drop in the use of hormone therapy by 2003. Now, the general rule is this: If you take hormone replacement therapy, aim for the lowest dose that proved helpful, for the shortest time achievable.

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What about estrogen alone (without progestin)?

Women who have had the removal of their uterus are potential candidates for estrogen alone (without the progestin). The scientists provided some answers in 2015 when they reported that estrogen alone led to a lower risk of breast cancer. In contradistinction, the combination of estrogen plus progestin raised breast cancer risk.

Update: Estrogen alone associated with more prolonged survival

The researchers recently provided long-term results, with just over 20 years of follow-up:

Estrogen alone use resulted in fewer breast cancer cases, with a drop by about a fifth (22 percent), compared with placebo. Also, estrogen alone is associated with 40 percent lower breast cancer mortality.

The use of the combination of estrogen and progestin drugs did not affect mortality but did increase breast cancer incidence by about 1.3-times.

I am impressed that estrogen alone (as hormone replacement therapy) dropped breast cancer incidence and mortality long-term. Even when we have used risk-reducing drugs such as tamoxifen, we have not seen a reduction in mortality.

Whether the use of different types (compared with those used in this study) of preparations of the hormones has the same effects is unknown. One criticism of the study is that high numbers of women quit their hormones during the study period. Finally, these women were well past from menopause. Whether the observation that estrogen reduces risk applies to younger women remains unknown.

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Might you benefit from HRT?

Before we go, I want to pivot to who might derive a benefit from hormone replacement therapy. If you are healthy, you might consider weighing the benefits of HRT against the known risks if:

  • Hot flashes. You have hot flashes that are moderate to severe. HRT is the most effective approach for hot flashes and night sweats related to menopause.
  • Other menopausal symptoms. If you have menopause-related itching, dryness, or pain with sexual intercourse, estrogen (such as a vaginal cream) may give you significant relief.
  • You have a high risk of bone loss or breaks. Those with osteoporosis may derive some protection from estrogen-based therapies. Usually, bone-building drugs such as bisphosphonates are preferred.
  • You entered menopause too early (for example, if you had your ovaries taken out before age 45.

Because estrogen can cause uterus cancer (and progestins can counter this risk), those with a uterus need a combination of estrogen and progestin approaches. Today, we focus on estrogen alone.

Reducing the risks of hormone replacement therapy

There are many forms of hormones. Estrogen may be delivered via a pill, patch, gel, vaginal cream, or a ring (or suppository) in your vagina. If your primary concern is vaginal dryness, care providers usually offer low-dose estrogen in a cream, ring, or tablet.

For those who take HRT, the general approach is to use the lowest effective dose. It should be taken for the shortest reasonable time. Regular follow-up with a valued healthcare provider is essential, as is appropriate cancer screening.

Finally, optimize your lifestyle. You know the drill:

  • Get adequate physical activity (aim for a minimum of the equivalent of a brisk walk for 30 minutes, five days per week)
  • Maintain a healthy weight
  • Eat a balanced diet
  • Don’t smoke
  • Limit alcohol consumption
  • Get adequate sleep of 7 to 9 hours duration daily

Those who have not removed their uterus (a hysterectomy) are not candidates for estrogen alone, as it can cause uterus cancer. For those with a uterus, progestin needs to be added to the estrogen to avoid excessive risk.

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Alternatives to hormone therapy

First, watch for triggers. These can include heat, stress, caffeine, alcohol, and spicy foods. Some benefit from mindfulness activities, such as paced relaxed breathing, or yoga. Other women turn to non-hormonal medicines for hot flash relief.

Those with vaginal concerns (such as dryness) may try a vaginal moisturizer or lubricant. Others prefer a prescribed medicine.

Bottom line

Hormone replacement therapy is certainly not appropriate for all women. If you consider it, please have an in-depth dialog with your health care provider regarding the risks and benefits of HRT. Ask about alternatives, too. We know that estrogen alone (as hormone replacement therapy) drops long-term breast cancer incidence and mortality.

I’m Dr. Michael Hunter, and I thank you for joining me today. I hope you have a joy-filled day.


I have degrees from Harvard, Yale, and Penn. I am a radiation oncologist in the Seattle area. You may find me regularly posting at

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