Menopause and the ongoing hormone therapy debate

By Sonia Nagda, MD, MPH


Hormone therapy: safe or not?

Hormone therapy is in the news again. Ten years ago, many experts decided that for most women entering menopause, the risks of hormone therapy outweighed the benefits. But some doctors and women’s health advocates continue to enthusiastically defend hormones.  So, who should we believe?

Why the continued debate?

In 2011 and 2012, articles came out questioning research that found hormones risky, and emphasizing the benefits of estrogen-only therapy. To understand the debate, it is important to understand the history of hormone therapy.

The first hormone therapy was estrogen (Premarin), and it was prescribed starting in the 1940s to cope with hot flashes, osteoporosis, and sexual dysfunction during “the change of life.” It was thought to not have any negative side effects for menopausal women. However, when uterine cancer rates started to increase, experts decided estrogen alone was only safe for women who had previously had a hysterectomy, and therefore had no uterus where cancer could develop.

Meanwhile, drug companies introduced a hormone treatment that combined estrogen and progestin, which did not cause uterine cancer.  This became popular and by the 1990s, most women were encouraged to start hormone therapy even before reaching menopause and then to take it indefinitely.  The goal was to “replace” the hormones that naturally decrease with age and thus prevent many of the symptoms of aging, including osteoporosis, memory loss, and heart disease.

However, when the U.S. Women’s Health Initiative (WHI) study results came out in 2002, they clearly showed that hormone therapy can increase a woman’s risk of developing breast cancer and stroke, and possibly heart disease and Alzheimer’s disease. In fact, the trial was stopped early because the risks of taking combined hormone therapy, including the risk of invasive breast cancer, were determined to be greater than the benefit of taking these drugs. The Million Women Study, conducted on women over the age of 50 in the UK, confirmed the U.S. findings, showing an increase in the risk of breast cancer in women taking combined hormone therapy, as well as among women taking estrogen alone. As a result, new guidelines told doctors to prescribe hormones to fewer women at “the lowest dose for the shortest time.”

The companies that sell hormone therapy quickly responded, offering support to doctors and women’s health advocates who were willing to defend hormone therapy despite the negative research findings.  These efforts have continued for the past decade and were documented in a 2010 article published in Plos Medicine. Wyeth, the maker of the combined hormone therapy, Prempro®, allegedly paid clinical researchers to put their names on medical journal articles that downplayed hormone therapy’s role in breast cancer and talked up unproven benefits, including improved memory, cardiovascular health, vision, and a reduction in osteoporosis and even wrinkles. Wyeth-funded studies also criticized established treatments, such as raloxifene for osteoporosis, suggesting that hormone therapy would be a safer and more effective treatment.

In 2011, an article criticizing the WHI study speculated about why the study might have found hormones to be harmful.  For example, the authors speculated that it was possible that women who guessed that they were taking hormones would be more vigilant about getting mammography, thereby detecting more breast cancer. All five authors reported consulting work with hormone therapy manufacturers.  This same group of authors also targeted the results of the Million Women Study, saying women with suspicious lumps or suspected breast cancer were more likely to join the study and get regular mammograms.

Estrogen-only therapy

Another recent study, funded in part by Wyeth, found that women with hysterectomies who took estrogen-only hormone therapy for about 5 years after menopause had a lower risk of breast cancer than women with hysterectomies who didn’t take estrogen. However, women with a family history of breast cancer and women who had one or more breast biopsies in the past due to benign breast conditions were more likely to develop breast cancer while taking estrogen than the placebo.

The authors, who include Wyeth consultants, believe that estrogen changes its ability to cause cancer into an ability to reduce cancer only if taken after a woman’s own estrogen production has stopped.  However, by that time many women will no longer be suffering from menopausal symptoms, so why would they take hormone therapy, which has other risks as well?  The authors conclude that women looking to reduce their risk of breast cancer should not take estrogen therapy, but rather take tamoxifen or raloxifene, which are hormonal drugs approved to prevent breast cancer.

Fewer women on hormone therapy led to declines in breast cancer rates

Breast cancer rates fell almost 7% in the U.S. during the years after physicians stopped prescribing hormone therapy so often. Were lives saved because fewer women were on hormones?  Most experts believe so, especially because the reduction in breast cancer was among women over 50 with estrogen receptor-positive cancer-the kind of breast cancer that hormone therapy “feeds.”

What are the alternatives to hormone therapy?

Menopausal symptoms can harm a woman’s quality of life, but there are ways to reduce those symptoms. For example, vaginal dryness and/or pain with sexual activity can be treated with a lubricant gel or moisturizer, or a vaginal cream with estrogen (which is safer than estrogen pills). Lifestyle changes (e.g. sleep, exercise, and diet) or alternative therapies, such as massage and acupuncture, can help reduce the symptoms of menopause. To treat osteoporosis, cardiovascular disease, and depression, select medications specifically targeted to these conditions, rather than relying on treatment with estrogen.

If you have debilitating menopausal symptoms, and you have no family or personal history of cancer, heart disease or stroke, hormone therapy may still be an option.  Choose the lowest dose and take it for the shortest time possible to lower your risk of breast cancer and other diseases.

For more information about menopause, click here.

For more information about hormone therapy and breast cancer, click here.

For more information about how drug companies pay authors to promote their products, click here.

Fugh-Berman AJ. “The Haunting of Medical Journals: How Ghostwriting Sold ‘HRT.'” PLoS Med 2010; 7(9): e1000335. doi:10.1371/journal.pmed.1000335.

Chlebowski RT, Hendrix SL, Langer RD, et. al. “Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women’s Health Initiative Randomized Trial.” JAMA. 2003; 289(24):3243-3253.

Million Women Study Collaborators. Breast Cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003; 362:419-27.

National Cancer Institute. .Menopausal Hormone Therapy and Cancer.

Shapiro S, Farmer RDT, Mueck AO, Seaman H, Stevenson JC. “Does Hormone Replacement Therapy Cause Breast Cancer? An Application of Causal Principles to Three Studies: Part 2. The Women’s Health Initiative: Estrogen Plus Progesterone.” J Fam Plann Reprod Health Care. 2011; 37(3):165-172.

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Anderson GL, Chlebowski RT, Aragaki AK. “Conjugated Equine Oestrogen and Breast Cancer Incidence and Mortality in Postmenopausal Women with Hyseterectomy: Extended Follow-up of the Women’s Health Initiative Randomised Placebo-controlled Trial.” The Lancet Oncology 2012; doi: 10:1016/S1470-2045(12)70110-9.

Ravdin PM, Cronin KA, Howlader N, et. al. “The Decrease in Breast-Cancer Incidence in 2003 in the United States.” New England Journal of Medicine. 2007; 356(16):1670-1674.