|“While it appears from the headlines that ‘new’ studies are being released, many people do not realize that these ‘new’ publications are actually more data from the same Women’s Health Initiative study that was first reported in 2002.”
Making Sense of the Hormone Hysteria
By Elizabeth Lee Vliet, MD
We have all seen or heard the ongoing negative headlines regarding “hormones” from the Women’s Health Initiative study. The first releases came out in the summer of 2002, and there have been several subsequent publications from this group.
While it appears from the headlines that “new” studies are being released, many people do not realize that these “new” publications are actually more data from the same Women’s Health Initiative study of women using Prempro (combination therapy with estrogen and progestin) that was first reported in 2002.
The Prempro group was stopped last year because of increased risks found with this product, similar to the concerns I have raised in my books for many years. The Premarin (conjugated equine estrogen alone) group of women did not have these risks, and the women in that group who had had a hysterectomy and could take estrogen alone, are continuing the study.
Since the Prempro part of the study was stopped, researchers are publishing only the data analysis from this group, not data from the women taking estrogen alone. Consumers do not realize is that it is common in academic medicine for the same study population data to be “mined” (or analyzed) for multiple publications on different topics. Rather than put all of the data analyses into one publication, a series of publications based on the same study group may be published over several years as the researchers consider different variables.
For women consumers, it is confusing, because it seems another revelation hits the news every other week. Unfortunately for consumers, the media headlines make it sound like this is yet another, different, study adding more fuel to the fire. In fact, it is simply more data from the same study, and the same combination of horse-derived estrogen and synthetic progestin being given to elderly women.
Most people are not aware that the average age of the women in the WHI was about 64, with 66% of the group over 60 and 21% over 70. This is 15-20 years later than hormone therapy is usually started to relieve menopausal symptoms or to prevent such problems as bone loss. In addition, 69% of the women were overweight or obese, with BMI above normal of 25 kg/m2. 36% of the women had high blood pressure, 4% were diabetic, and about 16% had a family history of breast cancer. Significant percentages of these women had other medical problems such as diabetes, high cholesterol (needing treatment with statin medicines), as well as histories of cardiovascular problems such as heart attacks, strokes, TIAs, and other evidence of vascular disease. The women are referred to in the title of the medical publications and in the press as “healthy”; yet most physicians –and most women who think about it – would not consider women with these health problems as being “healthy.”
And certainly, based on the International Menopause Society discussions, women with all of these medical problems would not be good candidates to use Prempro. I have described in my books some of the medical problems that can be aggravated by this dose of daily progestin with equine estrogens. Most of you have already heard me talk about the research that has shown the transdermal patch for estradiol and a form of natural progesterone are better options when these medical problems exist. Obesity is known to be an independent risk factor for breast cancer, and hypertension is known to increase risk for stroke and heart attack, so the presence of these medical problems, along with older age in the study group, can bias the study results more negatively.
As I have said in my books for many years, Premarin and Prempro used in the WHI are not the same hormones made by our body, and the WHI study is not looking at the difference in the types and routes of delivery for the many other forms of hormone replacement therapy available. News articles are also glossing over the fact that the risk increases reported from the WHI were seen only with the Prempro group (combined daily progestin and horse-derived estrogen), but not those taking Premarin (estrogen) alone. This is an important difference.
The women who had already had a hysterectomy and were taking only estrogen have not shown the increases in breast cancer or stroke seen in those taking progestin with estrogen (Prempro). Many physicians and researchers think these adverse outcomes are more likely due to the particular progestin being used (Provera or medroxyproges-terone acetate, MPA), since earlier studies have shown that MPA negates the beneficial effects of estrogen. I think these new results make it even more important that women who have had a hysterectomy avoid taking progestin or progesterone unless there is a clear medical reason to do so.
Another study presented at the World Menopause Congress in Berlin in 2002 found that when 1 mg 17-beta estradiol plus 0.5 mg norethisterone (progestin) was prescribed for high risk women with vascular disease, there was no increase in adverse cardiovascular risk, and in fact, a trend toward reduced CHD was seen. In Europe this product is called Activelle, in the U.S. it is Activella (17-beta estradiol + norethindrone).
A recently released (August 2003) study found that women using 17-beta estradiol transdermal patches had no increase in blood clots, while those using oral estrogens, such as Premarin, did have an increase. Leading menopause researchers have pointed out for many years that the type of estrogen and progestin used can make a big difference in outcomes, as I have seen in my own practice, and have been writing about in my books for many years.
And what about the “Million Women Study” from the U.K. – just published in August 2003? The headlines once again screamed that “hormones” cause breast cancer. But there are some crucial limitations of this study that the press did not report. First, it was a survey/questionnaire study of women’s responses, not a controlled clinical trial of medications. As one experienced researcher said to me after the Million Women Study came out: “People believe it (a study) by the sheer numbers, whether or not it is a good study! The more you measure, the less accurate the measurements tend to be!”
Second, when you have such a large number of participants, even very small differences will be statistically significant, but that does not always translate into clinical significance for you as an individual woman unless the amount of the difference is very great. As an example, the Million Women Study found that in the estrogen alone group, over ten years, there were 32 breast cancers in 1000 women who did not use hormones. Over the same ten year interval, there were 37 breast cancers in 1000 women if they used estrogen alone. So that’s 5 additional cancers in 1000 women over ten years. This is a very small increase in breast cancer. We have a far greater risk of dying in a car accident every day…yet how many of you have given up driving your car?
Third, a relative risk (RR) greater than 2 is usually the point at which we begin thinking that a particular medication has a causal connection with an unwanted outcome or side effect. In this study, it was only for the women who used the estrogen-progestin combinations for longer than 5 yrs that the data showed a RR greater than 2. All of the other groups of hormone users had a relative risk (RR) close to 1, which can be due to experimental error.
Fourth, the Million Women Study did not show separate data for 17-beta estradiol, our natural human form. They only broke out data for CEE (Premarin) and for the potent synthetic ethinylestradiol (EE) which is used in birth control pills and not typically for menopause therapy in the U.S.
There are other issues that you should be aware of as you read articles that condemn hormones based on this U.K. study. In the National Health Service in Britain, women only get mammograms every 3 years, not annually as in the U.S. And the British National Health Service only offers mammograms after age 50, not before. The standard in the U.S. is for women to have mammograms beginning at age 35, then annually after age 40. Also what struck me in reading the Million Women Study was that the average time between diagnosis of breast cancer and death in Britain was a very short 1.7 years! This is very unusual in the U.S. for the interval between diagnosis and death to be such a short time, so to me it suggests breast cancers in Britain were being diagnosed quite late, when they are less treatable. The national statistics further support this: in Britain, the average survival rate from breast cancer is 65% vs in the U.S. average survival is 85%.
We have many good studies published over many years showing important beneficial differences and better outcomes when 17-beta estradiol and progesterone or norethindrone are used instead of conjugated equine (horse) estrogens and MPA. I think that more natural hormone products, identical to what our own bodies make, will ultimately be shown to minimize the problems that were seen with Prempro, but there is still much research to be done to “prove” this, so new information will be coming out all the time. I make the effort to regularly attend the international meetings where the cutting edge research is being presented, and make information available to my patients.
In addition to summary points I have included in this letter, there are several excellent articles from Climacteric, the Journal of the International Menopause Society that may be accessed at the IMS website, www.imsociety.org, if you would like to read more detail on these important issues. An outstanding review of the issues was published in the “IMS Position Paper” on the WHI the September 2002 issue of Climacteric. There are also excellent editorials by Prof. A.R.Genazzani in the September 2002 and April 2003 issues of International Society of Gynecological Endocrinology Journal available on line. I have posted some comments about the WHI study on my website and in my new book, It’s My Ovaries, Stupid! (2003). In the book, I have included references for those of you who want to check out the original medical articles.
As I have stated in my books and many speaking engagements, I encourage you to evaluate your individual situation, your needs and quality of life, your risk factors and make an informed decision about what you want to do, rather than feeling scared or pushed into making decisions you are not comfortable with. The bottom line is that you need to decide what YOU want to do for your health and well-being, and decide if the risks (of anything you do!) are worth it, based on your values and needs.