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HRT And The “Window Hypothesis”: Hope Or Hype?

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.

Photo credit: Picasso’s Portrait of Dora Maar, from Musee National Picasso, Paris.

*This blog post was originally published at The Blog that Ate Manhattan*

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