Wednesday Bubble: HRT and the “Window Hypothesis:” Hope or Hype. Guest post c/o The Better Health Blog

Posted by on Apr 28, 2010 in HRT | 4 comments

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.


  1. 7-31-2010

    I read the Estrogen Dilemma and had the same experience at menopause as Cynthia Gorney had. Two gyns and one endrocrinologist said my estrogen was normal. I was so sick I thought I probably had leukemia. It was getting worse and worse over a period of about three months until my GP sent me to a rheumatologist. I had a pain in my left leg that was debilitating. None of these guys could connect my symptoms with menopause! I was just 51 years old, the classic age for menopause. The rheumatologist checked out my bones (OK) and asked, have you ever taken estrogen? No, but I’ll take anything. I took it and in TWO DAYS the pain in my leg stopped. I continued taking ERT and gradually over the next few weeks recovered. I was also having drenching night sweats. How truly bizarre that the gyns and other doctors had no clue. Your estrogen is Normal lady! I am now 80 years old and have taken HRT for 30 years, WITHOUT INTERRUPTION.
    This gets to be a long story. My mother died at 80 after 10 years of Alzeimers. The hypothesis of timing is an important breakthrough in thinking about AD. My idea is that the receptors for estrogen in the brain DIE OFF when they are deprived of estrogen at the time of either natural menopause or surgical menopause. When the receptors die or atrophy due to estrogen depletion, they cannot be reactivated or restored to life. Thus taking estrogen when AD has begin is of no use. Think about male pattern balding. The hair follicles die off (due to depletion of MALE hormones) and cannot be brought back to life EVER. Hence hair transplants!
    The researcher at USC is onto something, I think. I answer is under our noses. Needless to say, I don’t have AD. I teach English as a Foreign Language and have been doing so for the last 12 years as volunteer. I go to Italy almost every year, take Italian lessons (for 20 years) read the NYT and Wash Post every day and I can do the Sunday crossword in the NYT. I cook like Martha Stewart! I just had a “neck lift.” Everyone says it was a success! I also do not have osteoporosis. I’m a devout Liberal Democrat, which knowledge will tell you that I am quite sane. I’d like to know about studies of women who have taken estrogen for 30 years without interruption. How can I find out?

    • 7-31-2010

      Adele – the Women’s Health Initiative has been examining various health issues in women since 1991, and follow up continues, hence that’s 19 years of data. (Note however, that several of these trials have been halted due to serious adverse side effects.) The Nurses Health Study was stared in 1976 and continues to examine health issues in women, although the focus of both of these has not been solely on HRT. These are good places to start.


      It sounds as though you are in amazing health and I wish you continued good health. If you read Flashfree, you will learn that I am not a huge advocate of hormone replacement therapy. While replacing hormones may help with cognition (the verdict is still out on that), it can also significantly boost the risk of breast, ovarian and lung cancer, and lead to a host of other problems. I’ve completely shut down the night sweats through a variety of herbs, regular exercise and good diet. I love your story however.

      All the best to you and hope you will continue to comment!

  2. 7-31-2010

    Forgot to hit “Notify me of follow-up comments via email”!

    Please do that. Thanks

  3. 7-26-2011

    Window hypothesis was not clear to me before. I am glad to stumble upon this blog. Thanks for the post! All women must know about this.


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