Should women be taking estrogen to treat the effects of menopause? New research says yes.

Until about 20 years ago, physicians routinely prescribed the hormones estrogen and progestin for women after menopause, when levels of both of these hormones decline. This seemed like a logical treatment, and the hope was that it would slow down bone loss (osteoporosis), reduce the risk of heart disease, and treat other age-related problems. Estrogen also has the benefit of increasing sexual desire for women.

This all came to a screeching halt in 2002, when the Women’s Health Initiative published its first findings about the effect of estrogen and progestin. Although the initial results did show benefits for osteoporosis, the main finding, trumpeted loudly at the time by NIH and in various press releases, was that the combination therapy (both hormones) increased the risk of breast cancer. As the US Office on Women’s Health says today on their website, the 2002 study found that “women taking combination (estrogen and progestin) hormone therapy for menopause symptoms had an increased risk for breast cancer, heart disease, stroke, blood clots, and urinary incontinence. Although women using combined hormone therapy had a lower risk of fractures and colorectal cancer, these benefits did not outweigh the risks.”

It turns out that this was not the full story.

As detailed in a stinging rebuke by one of the principal investigators of the Women’s Health Initiative, Robert Langer, the announcement in 2002 was deeply flawed, and many of the clinical investigators were “shocked” and “aghast” when they saw the paper announcing the results, which they had no opportunity to comment on before it appeared. Despite many objections, NIH proceeded with a “highly publicized press conference, centered around the inflammatory press release... that pandered to women’s greatest fear–the fear of breast cancer.”

Not surprisingly, the use of hormone replacement therapy plummeted after that, and has remained low since.

Perhaps even more striking, as Dr. Langer wrote in 2017, was that results from the Women’s Health Initiative (WHI) trial of estrogen alone (not in combination with progestin), reported 2 years later, suggested that estrogen alone led to a reduction in breast cancer, and a reduction in coronary heart disease as well.

So it appeared that, despite all its flaws and its premature termination, the WHI study showed that estrogen therapy alone seemed to have major benefits. The problems (if there were any–the termination of the study makes this conclusion somewhat uncertain) arose with a combination of estrogen+progestin.

Another large study of hormone therapy, the Danish Osteoporosis Prevention Study (DOPS), also halted its efforts after the 2002 report from the WHI. However, those women had already been in the study for 11 years at that point, and the Danish scientists continued to follow them for up to 16 years. They reported their findings in 2012, and the results were quite the opposite of what the WHI had found. I’ll just quote them because their findings are so stark:

“After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke.”

These benefits were confirmed in 2020, when a long-term followup of the women from the original WHI study found that women who took estrogen (CEE, or conjugated equine estrogen) only had lower rates of breast cancer than women who did not.

Even more recently, in a yet-unpublished preprint, NIH scientists Seo Baik and Clement McDonald examined the records of 1.5 million women collected from the Medicare database, looking for the effects of estrogen-only therapy on the risk of cancer, heart disease, and death. They found that the use of estrogen-only led to a 21% reduction in the risk of death, and a similar reduction in the risk of breast cancer, endometrial cancer, and ovarian cancer. Combination therapy using both estrogen and progestin, in contrast, led to an increased risk of breast cancer.

The message now seems pretty clear: despite the hasty, scary announcements made by the Women’s Health Initiative back in 2002, the accumulation of evidence suggests that estrogen-only hormone therapy for post-menopausal women is likely to convey a range of highly significant health benefits, not only for breast cancer, but also for osteoporosis and heart disease. The benefits vary by age, and by whether or not women have had hysterectomies, but the overly simplistic idea that hormone therapy causes breast cancer is simply wrong.

The NIH Office on Women’s Health still has this wrong, but the Women’s Health Initiative website is much more up-to-date, featuring an announcement from 2020 that describes the “enduring protective benefit of estrogen-alone therapy.”

As with most medical treatments, the true picture is complicated, but millions of women today might benefit from estrogen. If you think you might be one of them, talk to your physician.

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