- Utian Speaks Out
- October 21, 2010
What is it about the WHI writing team that they can take data that they agree is not statistically significant, then reach the unjustified conclusion that with hormones as used in the WHI study, “breast cancer mortality also appears to be increased with combined use of estrogen plus progestin,” and finally through their lead author and others advise women that HT is really dangerous?
So what are the facts?
As with the initial publications, this longer follow up approximately 7 years after the original WHI EPT trial termination in July 2002, confirms a slight increase in incidence of breast cancer in women on combined continuous estrogen plus progestin therapy compared to placebo. Again, as in the first reports, there was a greater incidence of node positive cancers. The original reports confirmed no increase in overall all-cause mortality, but did not report separately on breast cancer deaths. At first blush, this paper would seem to be one leading to more banner headlines against use of postmenopausal hormone therapy, reporting that “breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.” However, one needs to read the paper carefully. There were 25 deaths in the HT group and 12 deaths with the placebo. The HR (hazard ratio) was 1.96 which is almost a doubling of the relative risk (I can just see the headlines – HT doubles risk of dying in postmenopausal women). But the CI (confidence interval) was 1.00-4.04. This wide spread includes 1.00 which makes the difference NOT statistically significant. Hence their statement in their conclusions that mortality “APPEARS to be increased.” For this reason it is totally appropriate to look at the absolute risk. This turns out to be 2.6 vs. 1.3 deaths per 10,000 women per year. By the WHO CIOMS classification, even if this was statistically significant, the increased risk would be classified as extremely rare.
So what do I take away from this? Firstly, the combined continuous use of estrogen plus progestin (at least the products used in the WHI) have an adverse effect on the breast, slightly increasing both the incidence of BC and possibly the chance of dying from it. While this increased risk is rare, it is mandatory on health providers to try “to do no harm” (Hippocratic oath). Fortunately, the good news is that the same WHI investigators just reported at the Asia-Pacific Menopause Society meeting in Sydney that estrogen when administered alone appears to have the opposite effect. That is, they apparently reported that the E alone group had a lower incidence of BC and mortality from BC compared to placebo. I await that publication with interest (but where and when will WHI publish good news?).
Secondly, the NIH and their WHI Writing Group should finally come out with a revised “Global Health Index” targeted specifically at the 50-59 year old group of women because they are the most likely to suffer from severe hot flashes and be prescribed hormones. If benefit on heart, bone, colon, diabetes, and possibly brain is taken into account, the balance of benefit to risk is likely to be quite different from all their previous looks at that score.
The conclusion is therefore that at least the progestin (MPA – medroxyprogesterone acetate) used in the WHI study is not beneficial to the breast and may cause harm. Other studies appear to indicate that alternate progestins or progesterone used in lower doses and intermittently may be safer, but there are no other studies of the size of the WHI and never likely to be.
Bottom line is that after all the hullabaloo over the past 9 years since the initial termination of the HT arm of the WHI, estrogen turns out to be quite safe, the MPA has a cloud of suspicion, and the future recommendation is for careful assessment on an individual basis for every women transiting menopause to determine health status, future risk for disease, and a decision based on a clear indication whether hormones are truly needed and recommended in her situation. If the affirmative, then current knowledge should be used to determine what dose, type, and route of administration should be used.
The WHI has succeeded finally in showing that postmenopausal hormone therapy has clear risks and rewards. The risks are rare, and it is up to every women for herself to decide based on a transparent explanation to her about the facts.
May I conclude that there is no better source for her to get these facts in a clear and unbiased way than from the NAMS website at www.menopause.org <www.menopause.org>
5 Comments
Every time another WHI knock-off article comes out and I’m assailed by patients, I begin to doubt my convictions and even my sanity. Then along comes Utian Wolf, my Hormone Hero, to save the day. Thanks again to Utian for his inimitable way of analyzing information and restating in a cogent manner what should be obvious.
Thank you so much for this post, Wulf. Estrogen does not “cause” breast cancer. I’ll continue in earnest to educate the larger public, as well as my patients, on the concepts of absolute risk as compared to relative risk. Also the magnitude of numbers matters, with these tiny differences of no meaning individually but important when placed in a larger context. Hopefully the upcoming trial results will help us further reassure the public that supportive small doses of estrogen are not only safe but critically important for optimal biologic balance and healthy aging for women.
Yours sincerely,
Ricki Pollycove
As usual, thanks for giving an informed perspective on HT. Two questions:
1) if the WHI women were 66ish when the study started then they should be 77ish now. They report 2.6 deaths per 10,000 women per year but the published rates put that age group more like 10 per 10,000. What’s up with that difference?
2) What does it mean that the current nleader of NAMS is the third author?
In the paper, the WHI does not report the mean or mean age of the group. As the original mean age was 63, at most the mean age here would be 70. However, they do state that “those re-consenting (To get into the follow up) were slightly younger and more likely to be white than those not re-consenting.” So you are technically correct that the incidence of mortality from BC is low in both the study and placebo group, the possible difference exists. Indeed they did not get statistical significance nor did they claim it in the paper. The chief WHI spokesman to the media nonetheless, warned of serious public health consequences etc. I believe it is time someone held his feet to the fire for shouting fire in a crowded theater!
Your second question you should address directly to NAMS.
Thanks for the comments
Wulf Utuan
Thank you, Dr. Utian for saying plainly what the WHI Estrogen only arm study revealed! Estrogen proved to be safe, it was the MEDROXYPROGESTERONE ACETATE, that seemed to be the problem. This was evident from the data but not directly discussed in the press.
I see daily, as a practicing Family Nurse Practitioner, that women are having complete TAH/BSO and are not being treated postoperatively with estrogen because their GYN MD feels estrogen causes breast cancer. The women are suffering from a myraid of menopausal symptoms and yet are afraid to do anything about it.
Your voice, as an expert in Menopausal Medicine, needs to be heard. I am so glad you are speaking out about this vital menopausal misconception.
Collinka