How is it possible that half of all gynecologists are still prescribing hormone replacement therapy to their patients for uses that are clearly unsupported by evidence – despite the alarming warnings of the largest randomized, placebo-controlled trial of HRT ever performed?
This reality is “curious”, according to Dr. Adriane Fugh-Berman at Georgetown University Medical Center, in a new study* examining 340 medical journal articles about HRT. Her research was published yesterday in the journal, Public Library of Science Medicine.
But even more curious are her findings that the majority of the doctors who have written pro-HRT papers for medical journals have been funded by the very drug companies that manufacture hormone replacement drugs.
These companies were financially hurt by 2002 results of the massive Women’s Health Initiative study, which meant an almost immediate catastrophic loss of sales revenue for manufacturers of all HRT drugs. Prescriptions dropped by 80% – a major blow to companies like Wyeth Pharmaceuticals, whose HRT drugs Prempro and Premarin had earned the company over $2 billion just one year earlier. (That still puts the net gain well ahead for the company, who has now settled a third of the pending lawsuits from women who developed breast cancer while on Prempro, after the company set aside over $772 million to resolve legal claims, according to Bloomberg).
Dr. Fugh-Berman now explains how pharmaceutical companies may have successfully begun to address and even reverse this loss of income by attempting to influence what doctors are learning about HRT since the WHI findings went public:
“The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. For example, of the 10 journal authors we studied who had written 4-6 articles each:
- eight were found to have declared payment for speaking or consulting on behalf of menopausal hormone manufacturers or for research support
- seven of these eight were speakers or consultants for the drug company
- 30 of 32 medical journal articles (90%) evaluated as promoting HRT were authored by those with financial conflicts of interest
- journal articles promoting the use of HRT were almost two and a half times more likely to have been authored by authors with financial conflicts of interest as by authors without conflicts of interest
- in articles from three authors with financial conflicts of interest, some of the same text was repeated word-for-word in different medical journal articles
We know that physicians read medical journals, and Dr. Berman reminds us that about half of gynecologists still continue to distrust the results of WHI while prescribing HRT for uses that are not supported by evidence.
She reported that common themes in journal articles, editorials and letters that were identified as “promotional” included:
- attacks on the methodology of the WHI
- arguments that clinical trial results should not guide treatment for individuals
- arguments that observational studies are as good as or better than randomized clinical trials for guiding clinical decisions.
- arguments implying that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or will be proven.
WHI, a major independent 15-year research program begun in 1991, reported that the demonstrated risks of HRT outweighed benefits in asymptomatic women. Risks were so clearly demonstrated, in fact, that the HRT study was stopped early. These findings on the use of estrogen-progestin and estrogen-only HRT drugs were alarming, according to Dr. Fugh-Berman’s team:
“Both therapies increased the risk of stroke, deep vein thrombosis, dementia, and incontinence; estrogen-progestin therapy also increased rates of breast cancer.
“Neither therapy reduced cardiovascular risk, and neither markedly benefited health-related quality of life measures.”
A follow-up study by the Canadian Cancer Society found there was a significant decrease of 10% in the rate of new breast cancers among post-menopausal women between 2002 and 2004 — coinciding with the drop in the use of HRT after the WHI study was published.
The Women’s Health Initiative found that women who take combined hormone therapy (estrogen and progestin together) have a higher risk of breast cancer. The data from this study also revealed that the longer women use combined hormones, the more their cancer risk appears to increase.
And follow-up results shared this past April have shown that taking:
- Progestin-alone HT does increase breast cancer risk, but
- Estrogen-alone HT for a short term does not increase risk of breast cancer (unless you are a cancer survivor taking estrogen-alone hormones shortly after completing your cancer treatment)
What about these “bio-identical hormones” that we’ve been hearing are safer and more effective than traditional HRT for menopause symptoms? Dr. Mary Gallenberg, who has been teaching at the Mayo Clinic College of Medicine and working as a consultant with Mayo’s Department of Obstetrics & Gynecology for over 20 years, answers uncategorically:
“No, they aren’t. Bio-identical hormones may in fact be riskier than standard hormone therapy, and there’s no evidence they’re any more effective. These hormones have become popular in recent years, partly because of celebrity endorsements and partly in reaction to reports of increased health risks with standard hormone therapy.
“The term ‘bio-identical’ means the hormones in the product are chemically identical to those your body produces. In fact, they are – but so are the hormones used in many FDA-approved hormone replacement products.”
Results of the massive WHI study were no surprise to many women’s health organizations, according to Kathleen O’Grady of the Canadian Women’s Health Network:
“We have been following the questionable methods used to promote the prescription of HRT to healthy midlife women.
“Short-term use of HRT has been documented in a variety of studies as a useful treatment for alleviating the temporary symptoms associated with the onset of menopause, such as hot flashes, night sweats and vaginal dryness.
“However, longterm use of HRT (more than 5 years), and the practice of prescribing HRT to healthy women – those not experiencing severe menopausal symptoms – is another matter.
“The WHI results are only the latest in a long series of studies demonstrating that longterm use of HRT should be considered only with extreme caution.”
If you’re like me, and you question even the term “hormone replacement therapy” – which somehow implies that, when diagnosed with the medicalized “disease” of menopause, our hormones need “replacing” in the first place – you’ll be interested in reading Dr. Fugh-Berman’s paper in the Public Library of Science Medicine. Or learn more on the Women’s Health Initiative FAQs page.
NEWS UPDATE: June 19, 2012
Pfizer Paid $896 Million in Prempro Settlements
Pfizer, the world’s largest drugmaker, has now settled about 6,000 lawsuits alleging Prempro and other hormone-replacement drugs caused breast cancer, and has set aside an additional $330 million to resolve the remaining 4,000 suits, according to a May 10, 2012 filing with the U.S. Securities and Exchange Commission. The reserve means New York-based Pfizer has now committed more than $1.2 billion to resolving claims that it failed to properly warn women about the menopause drugs’ health risk.
More than 6 million women took Prempro and related menopause drugs to treat symptoms including hot flashes and mood swings before a 2002 study highlighted their links to cancer. These hormone medications are still on the market.
* Fugh-Berman A, McDonald CP, Bell AM, Bethards EC, Scialli AR (2011) “Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women’s Health Initiative: An Analysis of Published Articles”. PLoS Med 8(3): e1000425. doi:10.1371/journal.pmed.1000425
Outstanding website, and this timely info is a must-read for all women. Doctors and their industry pals have successfully “medicalized” birth, death, pregnancy, menopause and other natural human functions that are now treated like diseases requiring medical intervention.
I agree 100% when you say: “even the term “hormone replacement therapy” – which somehow implies that, when diagnosed with the medicalized “disease” of menopause, our hormones need “replacing” in the first place…”
Except for short-lived severe unrelenting symptoms, menopausal women generally don’t need their hormones “replaced”. My doctor has been actively pushing HRT on me since I was in my 40s – – – implying that it’s some kind of universal wonder drug that all middle-aged women should take. I’m going to ask him if he’s read this PLOS Medicine journal article yet. Thanks for this.
Thanks for your thoughtful comments on my blog.
The reason why so many gynecologists (including myself) are still prescribing HRT is that it is a highly effective treatment for the vasomotor symptoms of menopause. Like all medication, it has risks as well as benefits, and some women make the informed choice to use it. Some of these women use it short term, others longer term, depending on their individual menopausal experience and symptoms.
I’ve posted my rules for prescribing HRT on my blog.
IMO, the problem is (1) those selling bioidenticals who misinform women that their products do not carry the same risks as Prempro, and prescribe it willy-nilly to women as an anti-aging fountain of youth (the very thing they accused Wyeth of doing for years…) and (2) Wyeth and other pharma continuing to feed the window hypothesis on HRT’s cardiac benefits into the medical literature – each article essentially repeating the one before – and discounting the breast cancer risks, which for most women are the most important concern when it comes to making a decision about treating menopausal symptoms.
Thanks again for posing me to the PLoS article.
One more thought –
The problem I have with the PLoS article is this –
“Dr. Fugh-Berman is also a paid expert witness on behalf of women who developed breast cancer while taking menopausal hormone therapy.”
A bit of the pot calling the kettle black if you ask me, when it comes to feeding the literature in support of your financial gains…
Thanks for your comments, Dr. Peggy. If I were one of the 8,400+ women who had sued Wyeth Pharmaceuticals after developing breast cancer while on Premarin or Prempro, I would hope I’d be able to get an expert witness like Dr. Fugh-Berman to testify on my behalf.
The “financial gains” of acting in this necessary role for such women seem hardly in the same league as the “financial gains” of Wyeth in their ruthless goal of achieving $2 billion annual sales targets. And as Dr. Fugh-Berman explained, the PLoS article “does not critique the appropriate prescription of hormones for hot flashes, but addresses the perplexing question of why physicians resist the conclusions of the Women’s Health Initiative, the definitive study of HT in asymptomatic women.”
I too have had my ob/gyn actively try to push Premarin on me after surgical menopause (I was 48) though I had no symptoms to merit it. This was especially puzzling as there is a history of breast cancer in my family.
Even if I had symptoms, and even if Premarin were safe, I would not take it because of the methods used to gather the horse urine used in its manufacture. I can’t see abusing any animal like that to create a med for a non-life threatening condition. Ethics aside, I question how well the human body can utilize estrogen from another species. The episode left me questioning my doctor’s knowledge, judgement, and ethics.
My unscientific observations of friends and relatives who’ve tried HRT leave me very unimpressed with it.
The side effects, the struggles to find the right product and the right balance, resembled alchemy more than medicine. Putting off the inevitable and dragging out the estrogen dependence makes HRT seem like a hormone methadone program.
Thanks Andrea for your unique perspective here. As I wrote, even calling this “hormone replacement therapy” somehow implies that, when diagnosed with the medicalized “disease” of menopause, our hormones need “replacing” in the first place.
Is the gynecologist who comments above aware that Premarin is being advertised in many women’s magazines such as “Women’s World”, “Taste of Home” as well as on many websites that women are likely to access? I haven’t seen them on TV but this level of advertising can make women think this is an everyday product. Pfizer is advertising this to likely consumers much more frequently than Wyeth ever did prior to their merger.