The follow up report on the Women’s Health Initiative’s (WHI)—Estrogen Alone Study was published this week in the Journal of the American Medical Association, and once again the media is having a field day! You didn’t have to look far to find confusing and contradictory headlines such as: “Hormone therapy for menopause symptoms: safer for some?” or “Estrogen Lowers Breast Cancer and Heart Risk in Some”

The first WHI study results, published in 2004, reported on the effect that estrogen had on women who had had a hysterectomy. At this point, the researchers were looking at what took place after the women had taken the drug an average of 3.5 years. They found that the women on estrogen had a decrease in fractures and an increase in stroke and blood clots compared with those on the placebo. They also found that estrogen did not reduce or increase a woman’s risk of having a heart attack. In addition, the findings suggested that estrogen might also decrease breast cancer risk.

The current report looked at the same women 10 years after entering the study and five years after they stopped taking estrogen. It showed that most of the benefits and risks associated with estrogen stopped when women discontinued taking it. However, a small decrease in breast cancer risk persisted.

This decease is interesting, but it’s hard to interpret. Did it occur because some of the women had their ovaries removed when they had their hysterectomy, which would also have significantly lowered their breast cancer risk? Unfortunately, the study report doesn’t differentiate between women who had their ovaries removed and women who did not—so there is no way to know the answer.

Even so, this report is still good news. It means that women who have had a hysterectomy can safely take estrogen alone for a short time (about 3.5 years) and they might also experience a potential decrease in breast cancer risk. It does not mean that long-term use is safe and indeed studies have suggested that long-term use still increases breast cancer risk albeit less than that of combined hormones. And it doesn’t address young women who have to have a hysterectomy.

Some reporters have suggested that studies like the WHI just confuse women. I beg to differ. First of all, the WHI’s Estrogen Plus Progestin Study clearly showed the danger of taking this combination after menopause. The year after the report came out the incidence of breast cancer decreased 8% in the United States and in all of the other countries where combination hormone replacement therapy had been widely used. Lives were saved because of this study!

Secondly, the purpose of research is not to confirm what we think we know but rather to find out whether it is true. We originally assumed that the ovaries stopped functioning at menopause. This was based on the fact that hormone levels were hard to detect in the blood with the techniques available at the time. But that assumption was wrong! The ovaries continue to produce small amounts of estrogen as well as the precursors of estrogen, which are made into the hormone in the organs themselves. When estrogen replacement caused uterine cancer we assumed that the progestin we added would only affect the uterus and not any other organs. But this assumption was also wrong! We now know that the combination is worse for the breast. Without research, we would still have those additional breast cancer cases.

Our understanding of what estrogen does in the breast has been challenged by this research because these findings suggest that short-term estrogen use results in some breast cancer protection. And this is the type of unexpected finding we need, because it forces us to relinquish our assumptions, which is what moves science forward. We fought in the nineties to have more research on women, so let’s not complain when the data doesn’t always come out the way we think they should!
As scientists go back to the drawing board to try and figure out what this research means, we should give thanks to all the women who participated in these studies. If we all take advantage of every opportunity to be part of research, the answers we need will come more quickly. I started the Love/Avon Army of Women to give women an easy way to find out about these studies. Now it is time for you to do you part and join me!

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7 Responses to Postmenopausal Hormones and the Benefits of Research

  1. Jonathan Raymond says:

    To piggyback off of Dr. Love’s take, I think what I find most bothersome about the reporting and interpretation of the new research in JAMA is how certain positive subgroup analyses took precedence over other negative ones.

    Despite the overall neutral effect observed in the study after women discontinued estrogen therapy (with the exception of the 23% lower risk of breast cancer), Dr. LaCroix, the study’s lead author, extolls the “benefits” of estrogen for women in their 50s and pay no attention to the opposite finding of increased cardiovascular risk seen in those over 70. I guess the reasoning is that it doesn’t really matter because it’s only women in their 50s who would even be started on estrogen in this day and age. But the implication, though not explicit, is that these drugs are safe to take from middle-age onward. What the headlines do not mention is that the JAMA paper pointed to other data that totally call into question as to whether or not the age effect even exists.

    At the very end of the paper right before the discussion section, some attention is given the COMPLIANCE/ADHERENCE model used after participants began stopping their study pills. As Dr. Colditz’s editorial made clear, nearly 60% of the women had stopped taking their pills before the study was prematurely terminated and this factor brought the average duration of use down to 3.5 years, not the 7.1 years of the entire trial. Added to that, when the researchers stratified the participants based on which women were still taking their pills and/or which ones were taking >80% of their pills, a different picture emerged – 1. no age difference was seen for any cardiovascular or cancer outcome, both during and after treatment 2. the breast cancer risk, during and after treatment, was indeed 32% lower BUT the risk of stroke was still 50% higher, both during and after treatment.

    Funny thing how this subgroup analysis seems to invalidate the positive one that has been reported is completely glossed over. And, more importantly, it makes it a definite possibility that age-splicing, which the WHI was not designed to test for, is not scientifically valid, or at least, questions the absolute certainty of any subgroup analysis. Does seem you really can get the orientation you want based on personal b

    Data on breast cancer mortality have also not been analyzed, but a worrisome finding back in 2004 showed that, despite the 23% lower risk of breast cancer seen with estrogen alone, there was a much higher incidence of larger tumors, node+ tumors, and problematic mammograms, findings mirrored in the Prempro arm of the WHI.

    I just hope women remain cautious and are not swayed by thinly-veiled attempts to reinstate the drug as some all-purpose, magical preventative. (Several of the study authors reported conflicts of interest.) They’ve already been down that road, one that lasted 40 years!

  2. Marjorie Pastalaniec says:

    Thank you for giving a deeper analysis of this study.

  3. Pink Kitchen says:

    Jonathan:
    I am so glad for your comments. Data from empirical studies can become so watered-down or misinterpreted by the time they reach the media, particularly in a country that has such a heavy focus on pharmaceutical solutions.

  4. When you are presented with a study you learn a lot of things. Health research is very important in today’s world where we are faced with a lot of uncertainty. Thank you for dedicating a spot in your blog to talk about this topic.

  5. Angela Garrett says:

    Isn’t the bottom line that we still don’t know enough about options for women with hormone changes that come with aging? And shame on us for that. The loss of hormones creates real health threats that are every bit as potentially debilitating and ultimately fatal as the ones associated with use of hormone substitutes. Enough with analyzing what doesn’t work! Please give that energy to exploring solutions.

  6. My question for Dr. Love or anyone who may know, I am a breast cancer survivor for 12 yrs. I am 60 yrs old and had a hysterectomy 5 yrs ago due to the Tamoxifen I took for 5 years after my lumpectomy. I had a estrogen/progesterone, positive type breast cancer. It was detected early and radiation was all that was needed after surgery. Now, I am so dry, everywhere, my GYN told me after my pap test my insides were like a 80 yr old woman! I am fit, 5’8″ 150 pds (trying to lose some)and have the famous “muffin Top” thanks to no Estrogen. I would love to be able to take it, just to see if it helps my syptoms (hot flashes, dryness etc) I am on Vitorin for high Cholesterol and have very low blood pressure.
    In the study I read, it mentioned Estrogen suppments lowered the risk of breast cancer. I was told not to take any supplements due to my positive breast cancer. Does this study mean I can take it? If only for 3 or 4 yrs it would be a great help. Please answer as my drs in Nebraska are very slow with anything new.
    Thank you, Janice Schlein

  7. Dana Isherwood says:

    Janice: Has your doctor suggested Vagifem for vaginal dryness or atrophy? This is a low dose estrogen tablet placed in the vagina. My oncologist is comfortable with my using them and I have had breast cancer twice. The Vagifem worked well for me.

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