Researchers in the UK recently published the results of a worldwide analysis on menopausal hormone therapy and breast cancer risk in the Lancet.[1] The analysis included 58 studies, published between 1992 and 2018, of over 100 000 postmenopausal women with breast cancer. They found that women who had ever taken hormone therapy had a higher incidence of breast cancer than those who had not.

Now, these findings are significant and published in a reputable journal, but they are nowhere near as astonishing as the news media portrayed them to be.

Immediately after the results, sensational and fear-provoking interpretations appeared in the headlines. The Telegraph reported, “HRT raises breast cancer risks by a third, major Oxford study finds,” and the Guardian read, “Breast cancer risk from using HRT is ‘twice what was thought.’” The Independent conveyed, “Menopausal hormone therapy linked to greater breast cancer risk for more than a decade after use.”[2-4]

These headlines might entice readers, but they certainly do not help women.

As doctors, we are continually challenged to interpret scientific research and then distill the relevant parts into language that our patients understand. Sometimes, however, we are merely a second opinion to the media. Like it or not, Dr Google has become the most accessible medical resource in the world. So when our patients get bad information online before they see us, it makes our job that much harder and, more importantly, it compromises their health care.

A brief history of menopause and hormone therapy is required to understand the impact of these recent titles. Menopause is a normal stage of life for women. A girl is born with a finite number of eggs that decrease over her lifetime until there are none left, and she enters menopause. On average this happens around 51 years old, but anywhere from 45 to 55 is normal.

While some women navigate this major life event without issue, 60% to 80% of women will encounter symptoms that worsen their quality of life.[5,6] Hot flushes, night sweats, trouble sleeping, memory problems, and depressed mood are some of the most common concerns. These symptoms stem from the abrupt loss of estrogen, normally produced by the ovaries, and the body’s struggle to re-equilibrate. Although they are not life threatening, these complaints should not be dismissed as trivial.

For example, menopause in one of our patients, a lawyer, led to unpredictable sweats that caused her to appear distracted and nervous in the courtroom. She chose to take hormone therapy to help ease her body through the transition and credited it with keeping her fast-paced career on track. Another professional, a surgeon, could not practise because sweat from her face would drip into patients’ open incisions. She also chose hormone therapy to allow her career to continue.

Hormone therapy mitigates menopausal symptoms by giving back a small dose of estrogen. Contemporary regimens most commonly involve an estrogen patch, gel, or tablet. Doctors individualize the amount to find the lowest effective dose for each woman. Unless the woman has had a hysterectomy, she would also be prescribed progesterone to limit the growth of the uterine lining, which could otherwise cause bleeding.

In the 1990s hormone therapy was common. After the results of the Women’s Health Initiative (WHI) study in 2002 and 2004, however, the number of women starting hormone therapy dropped from 1 in 12 to 1 in 20.[7-9] Furthermore, of the women already taking hormones when the WHI study was released, one in five stopped them. Among the main reasons they did so was media reporting.[9]

It is imperative that we step back and examine how we explain medical research to the public. Framing the results of a study with the appropriate context and magnitude can drastically change how people read them.

When we teach medical students about research, one of the most important principles of critical appraisal is interpreting the real-life risk. In statistical terms this is referred to as the absolute risk versus the relative risk. Relative risk is usually the less useful but more dramatic statistic—the one often cited in headlines. To illustrate with a simple example, a headline that reads, “double the risk of dying” (a relative risk of 2.0) might actually be referring to an absolute risk of 1% going up to 2%.

In this UK study, the relative risk conveys how often the event (i.e., breast cancer) happened in the hormone therapy group versus the group that did not take hormones. Women 50 to 54 years old currently using hormones had a relative risk of 2.1, which can be interpreted as being twice as likely to get breast cancer. That sounds pretty scary to most people. Fortunately, doctors are trained to rely on the absolute risk. It is much more meaningful as it refers to the probability of breast cancer in a population of women exposed to hormone therapy.

The authors of the Lancet study actually did an excellent job of stating the absolute risks on the front page. Unfortunately, media headlines did not focus on that paragraph. The conclusion was that taking estrogen and progesterone for 5 years was associated with one additional breast cancer in every 50 women.[1] To put things in perspective, that is actually a smaller risk increase than drinking alcohol, not breastfeeding, or being overweight.[5] Furthermore, as the North American Menopause Society emphasized, these results are observational associations rather than cause-and-effect conclusions, which are normally restricted to randomized controlled trial.[4,10]

The problem, as with our periodic “pill scares” related to birth control pills, is that bad news grabs a reader’s attention but good news does not. In emphasizing an arguably small (and previously known) risk of breast cancer when framing a story about hormone therapy, we are missing the big picture. Menopausal women take hormone therapy because it makes their lives tolerable and their careers manageable, not because they really want to take it.

The commentaries that have appeared in response to this recent report all stress the importance of individualized decisions for women considering hormone therapy, and that’s as it should be.[10,11] No menopausal woman should take hormone therapy without a careful assessment of her individual risk and the potential benefit, conducted with a knowledgeable care provider. Women and health care professionals should not be alarmed by the latest news. To quote a recent statistician’s words in the New Yorker, “How impressed should we be by very strong evidence for a very weak effect?”[12]  
—Caitlin Dunne, MD
—Timothy Rowe, MBBS, FRCSC, FRCOG

References

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

2.    Bodkin H. HRT raises breast cancer risk by third, major Oxford study finds. Telegraph. Accessed 8 October 2019. www.telegraph.co.uk/science/2019/08/29/hrt-raises-breast-cancer-risk-third-major-oxford-study-finds [10].

3.    Boseley S. Breast cancer risk from using HRT is ‘twice what was thought.’ Guardian. Accessed 8 October 2019. www.theguardian.com/science/2019/aug/29/breast-cancer-risk-from-using-hrt-is-twice-what-was-thought [11].

4.    Massey N, Crew J. Menopausal hormone therapy linked to greater breast cancer risk for more than a decade after use. Independent. Accessed 8 October 2019. www.independent.co.uk/news/health/menopausal-hormone-therapy-breast-cancer-risk-decade-after-use-a9084661.html [12].

5.    Gallagher J. Breast cancer: Menopausal hormone therapy risks ‘bigger than thought.’ BBC News. Accessed 8 October 2019. www.bbc.com/news/health-49508671 [13].

6.    Reid R, Abramson BL, Blake J, et al. Managing menopause. J Obstet Gynaecol Can 2014;36:830-833.

7.    Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-333.

8.    Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.

9.    Crawford SL, Crandall CJ, Derby CA, et al. Menopausal hormone therapy trends before versus after 2002: Impact of the Women’s Health Initiative Study Results. Menopause 2018;26:588-597.

10.    Faubion SS. NAMS Responds - Lancet article on timing of HT and breast cancer risk. Accessed 8 October 2019. www.menopause.org/docs/default-source/default-document-library/2019-08-30-lancet-article-on-timing-of-ht-and-breast-cancer.pdf [14].

11.    Kauntiz AM. Menopausal hormone therapy: Let the women decide. Medscape. Accessed 8 October 2019. www.medscape.com/viewarticle/919243?nlid=131942_904&src=WNL_mdplsfeat_191008_mscpedit_obgy&uac=212025CG&spon=16&impID=2123360&faf=1 [15].

12.    Fry H. What statistics can and can’t tell us about ourselves. New Yorker. Accessed 8 October 2019. www.newyorker.com/magazine/2019/09/09/what-statistics-can-and-cant-tell-us-about-ourselves [16].

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Dr Dunne is a co-director at the Pacific Centre for Reproductive Medicine in Vancouver and a clinical assistant professor at the University of British Columbia. She serves on the BCMJ Editorial Board. Dr Rowe is an associate professor at the University of British Columbia, former Editor-in-Chief of the Journal of Obstetrics and Gynaecology Canada, and a former BCMJ Editorial Board member. He is a recognized expert in menopause and hormone therapy.