Wednesday Bubble: HRT and the “Window Hypothesis:” Hope or Hype. Guest post c/o The Better Health Blog
HRT and the Window Hypothesis. Sounds a bit daunting, doesn’t it?
I was awed and inspired by this post on HRT, which was written by Dr. Peggy Polaneczky and appeared on the Better Health Blog on April 21. As the author states, Pfizer (formerly Wyeth), the maker of Premarin, is working furiously to frame the HRT argument around the Window Hypothesis, which refers to the time period in which a woman must start HRT in order to fully gain its benefits. Is the Window real? Or another mother of all inventions to convince women that HRT is as necessary as a daily vitamin?
So, dear readers, I’ll leave it to you to decide. Despite the length of the post, I am including it in its entirety because the issue is so important. I’d also like to state that I am grateful to Dr. Val Jones, the founder and CEO of Better Health, LLC, who has graciously granted me permission to repost the piece on Flashfree.
It’s only Wednesday, and so far three patients have come to their office visits carrying Cynthia Gorney’s article from Sunday’s New York Times entitled “The Estrogen Dilemma.”
The article explores the stories of three women who found relief from perimenopausal symptoms by using hormone replacement, framing the discussion in the larger context of what is being called the “window hypothesis” — the idea that starting estrogen replacement in the perimenopause and continuing it into later life may be neuroprotective and even cardioprotective, in contrast to beginning its use 10 or more years after menopause, where it can trigger heart disease, stroke and dementia.
The window hypothesis is one way of explaining away the findings of the Women’s Health Initiative, and goes something like this: “The WHI enrolled women who were too late into menopause to benefit from estrogen. If we had instead studied women starting estrogen at the right time, namely the perimenopause, we would have found that it protects against heart disease and Alzheimers.” Or as I explain it to my patients: “Think of it like exercise. If you work out vigorously and regularly from a young age, you can prevent heart disease. But take an overweight, out of shape 65 year old and have him/her run full out and you could trigger an MI.” (It’s a crude analogy, but it works.)
The Times article does a good job framing both the hope and the hype around the window hypothesis, and the dilemma it appears to pose for women entering menopause today, which is this: If you wait for data that proves the window hypothesis is right, by the time the results are in, you’re outside the window and it’s too late to start HRT. If you start HRT now and the hypothesis is proven wrong, then you’ve been taking medication with potential risks for years without any benefit. Or as author Cynthia Gorney so succinctly put it:
“If I make the wrong decision about this, I am so screwed.”
The pharmaceutical industry, particularly Wyeth, the maker of Premarin, is, not surprisingly, working hard to get the word out about the window hypothesis. Indeed, several of the researchers working on the hypothesis who are quoted in Gorney’s article have ties to Wyeth. At the risk of further hyping a hypothesis that may prove to be unfounded, I encourage you to read the Times article, and then take the time to peruse the intelligent discussion in the comments section. If anything it is testimony to just how well-informed the American public has become about HRT.
I myself have been hearing about the hypothesis for years now, but have yet to see definitive data to prove it. Fortunately, there are studies in progress that may settle the question within the next few years. But even if the window hypothesis proves to be correct, it will not mitigate the risks of breast cancer that accompany long term estrogen use in the menopause. That risk remains, in my opinion, the biggest concern for my patients when it comes to HRT, and it is surprisingly downplayed in the Times article.
The biggest problem I have with the article is that Gorney’s experience with both menopause and HRT is anything but typical. Most women get through the transition without major mood issues, although crankiness and irritability are common, especially in women who are not sleeping because of night sweats. When true depression hits, as it did for Gorney, antidepressants are needed, with or without HRT (Gorney takes both). I have seen the occasional woman who declares “I am back!” after starting HRT, and one particularly memorable patient whose depression was cured, but this is the exception, not the rule. Most perimenopausal women who take HRT are just relieved to be able to sleep through the night or get through a meeting without hot flashes.
But most importantly, what does Gorney’s individual experience with HRT and mood have to do with the window hypothesis? She is not taking HRT to prevent Alzheimer’s or heart disease, she is using it to augment the effects of her antidepressants. The whole window discussion thing is distracting from the real question at hand for her, which is sinply this: How long should she take HRT? That depends, not on whether the window hypothesis is true, but on how she feels when she tries to stop taking HRT.
If I were Gorney’s doctor, I’d be focusing her off the window hypothesis and onto why she is taking HRT in the first place — for emotional well-being. Now that it’s been a few years on the stuff, I’d say, let’s lower your dose and see how you do. If you do well, then stay on that dose for 6 months to a year, then go off and see if you still need it. Based on Gorney’s experience with occasional missed patches, I’ll predict she’ll still need HRT, but will be able to get away with a lower dose. But if she feels just as well off HRT, then I would advise her to stay off. Do everything else she can do to prevent heart disease – diet, exercise, low salt, get enough sleep (you know the drill.)
As for using estrogen to prevent Alzheimers, well, that’s a big leap of faith that I for one am not yet ready to take. Which does not mean that I don’t have an occasional patient (usually a scientist) taking HRT because she hopes it will prevent Alzheimers. Such women, in my experience, are much less worried about breast cancer than about cognitive decline, in an attitude similar to that of Julia Berry, one of the women profiled in the Times article, who had this to say:
“I could have my breasts removed. I like them. But they’re not my life.”
Recent data suggests that Berry may not need to make this Sophie’s choice between her brain and her breasts. The mental confusion so many women experience in perimenopause may in fact resolve itself once we come out the other side, irrespective of hormone use. This suggests that it is the widely swinging hormones of perimenopause that pose the most trouble for women, but that once things settle down, so do we.
Now that’s a window hypothesis you won’t hear Big Pharma talking about.
Read MoreWednesday Bubble: the soy controversy
Do they or don’t they?
Soy isoflavones have been touted as beneficial in everything from improving body composition and lowering breast and colorectal cancer, to addressing menopausal hot flashes and moods. You can read about some of these findings on Flashfree. This week, Reuters Health reported that eating foods rich in soy protein (i.e. 25 grams of soy protein and 60 mg isoflavones) daily did not provide favorable responses from blood fats, implying that soy has little benefit in terms of lowering cholesterol levels and in turn, promoting heart health.
Are you confused yet?
Increasingly, women are turning to soy and other compounds as alternatives to estrogen and hormone replacement therapy, which mounting evidence shows can be associated with a broad range of risks including increased breast, lung and ovarian cancer to heart disease. And yet, findings from clinical trials examining soy are often contradictory, making it difficult to come to any firm conclusion about its benefits.
What’s the problem? Well, researchers say that part of the problem is poorly designed studies, small number of study participants, wide range of ages and years from menopause, studies that don’t examine the pros and cons of an agent or strategy for a long enough period of time (i.e. longer than a year). In other cases (as I’ve argued previously), the study design does not account for certain factors that are critical to a therapeutic strategy, for example, the opportunity to clearly focus an intervention so that individual factors are accounted for (this was borne out by findings from a trial that examined and provided evidence for the role of acupuncture in easing hot flashes).
There’s good news though! Researchers finally appear to be getting their act together on the soy fron. They’ve announced that they are conducting a well-designed, large trial of soy phytoestrogens. Called SPARE (Soy Phytoestrogens as Replacement Estrogen), this new study will be looking at the effects of 200 mg soy versus sugar tablet daily — namely on bone health and symptoms — in 248 menopausal women over a two- year period. They will also be taking daily calcium carbonate plus vitamin D (in ranges of 500 mg to 1000 mg calcium and 200 to 400 IU vitamin D, depending on previous intake).
The study is specifically geared towards looking at spine bone density, but will also be looking at hip density, thyroid levels, menopausal symptoms, mood changes, depression, and quality of life, as well as any changes in blood fats. Study participants are between the ages of 45 and 60 and are within five years from menopause. What’s more, the researchers have also included a large percentage of hispanic women, which allows them to focus on how soy affects this minority group (Notably, the large multiethnic population of women in this study includes Asians, Blacks and Caucasians.)
The researchers say that they hope that the results of SPARE will provide a range of information that is especially relevant to Boomers reaching menopause. They also note that the dose of soy isoflavones being studied is much larger than what’s been studied in previously and are roughly twice that typically consumed in the Asian diet.
I realize that this post is pretty scientific. But what makes it most relevant is that it appears that researchers are finally starting to design studies that might actually show benefit of some of the alternative strategies we have available to us on the market. For those of you who insist on calling these alternatives “snake oil,” all I can say is ‘stay tuned.’
This bubble might finally be shattered; perhaps all that is needed is a better understanding of what it needs to test these substances appropriately.
Read MoreEvery breath you take…lung cancer and HRT
Remember last year’s post on hormone replacement therapy and increased risk of deaths from lung cancer? Researchers now report that HRT that combines estrogen and progestin can increase the risk for developing lung cancer, especially when used for long time periods.
In the latest nail in the HRT coffin, researchers evaluated 36,588 peri- and postmenopausal women between the ages of 50 and 76 over six years. During the study, 344 women developed lung cancer. Overall, the findings showed that the longer women took HRT, the higher their risk for developing lung cancer, with use of 10 years or more associated by as much as a 50% increased risk. Note that while an increased risk for developing lung cancer was also seen in women used HRT for up to 9 years, it was about half as much, or 27%.
While the researchers are quick to point out that this study does not prove that HRT causes lung cancer, it does show that taking HRT for certain periods of time can significantly increase the risk for lung cancer, even when other important factors are removed from the equation. Similar increased risk has not been observed in women taking estrogen alone.
In the latest position statement on hormone replacement therapy from the North American Menopause Association, a panel of experts currently conclude that the evidence shows that both smoking and age played an important role in promoting growth of existing lung cancers in women taking HRT, in particular among older women. On the other hand, they say that other studies suggest that HRT theoretically lends some protection against lung cancer in younger women.
Clearly these data are at odds. However, as a wonderful report in Reuters points out, the latest study ‘sheds light on the question’ because it looks at HRT use over a longer period of time.
Every breath you take…could eventually be your last. It all depends on your decision about HRT. Is the short-term gain worth the long-term risk? Only you and your doctor can evaluate your individual risk and determine if HRT is the right choice.
Read MoreWednesday Bubble: Another nail in the coffin for HRT
Still hearing that HRT can’t hurt your heart? Findings from yet another study, this time published in the February 16 edition of Annals of Internal Medicine, confirm the dangers that HRT poses to your heart, especially in the short-term.
In this latest analysis, researchers evaluated data derived from 16,608 postmenopausal women enrolled in the Women’s Health Initiative trial who still had their uterus. The findings?
Compared to women who had never used hormone replacement therapy, those who had used it continuously over 10 years had more than twice the risk of developing heart disease over the first 2 years, and more than 1.5 times the risk over the subsequent 8 years. For women who started hormone therapy after 10 years of entering menopause, there was also a trend towards developing heart disease over the first 2 years. Of note, researchers did observe a possible protective effect after 6 years in the women who started therapy closer to menopause as risk did start to level off at this time.
The upshot is that the first two years of taking HRT can be a dangerous time for women regardless of whether they start hormones closer to menopause.
Another nail? Yes, I’d say so.
But don’t take my word for it. Knowledge is power. Educate yourselves. And if you’d like to learn more about heart disease and menopause, I’ve written about it numerous times on this blog. I also encourage you to visit the American Heart Association website. Finally, I’d love for you to take a stand. Don’t you think it’s time for the FDA to start paying attention? These drugs are dangerous for women. Yet, they remain on the market and are prescribed daily. Whose nail, whose coffin?
Read MoreUnchain my lungs…estrogen and asthma
As the evidence continues to accrue against the use of combined hormone replacement therapy (HRT), attention must be turned to estrogen-only hormone replacement therapy. However, is it safer?
In the Women’s Health Initiative, which was halted last decade, taking estrogen alone was associated with an increased risk of blood clots, stroke, impaired cognitive function and dementia. In the latest bit of information to hit the news, estrogen-only therapy may also increase the risk for developing asthma.
Results of a 12-year study among almost 58,000 women who were not suffering from asthma at the start of menopause showed that they were 21% more likely to develop asthma symptoms. This risk was significant among women who had been taking estrogen only compared to women who had never used hormones, had a 54% greater risk of developing asthma. The risk was even greater among women who had never smoked, although a small proportion of study participants had allergies prior to developing asthma.
Once again, Reuters has done an excellent job of reporting on this study and has some great quotes from the researchers as well.
Meanwhile, what should you do if you’ve been taking estrogen to combat the symptoms of menopause? As always, you have a choice and only you and your practitioner can determine if you are at risk for developing any of the conditions that are associated with hormonal therapy. The good news? Breathe easy. Yet another reason to lose the hormones…for good.
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