The Estrogen Dilemma – Hope, Hype or Just One Woman’s Story?

It’s only Wednesday, and so far three patients have come to their visit carrying Cynthia Gorney’s article from Sunday’s NY Times called the “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 cardio protective, in contrast to beginning its use 10 or more years after menopause, where it can trigger heart disease, strokes 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”.

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 Gorneys 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…
Picasso’s Portrait of Dora Maar. From Musee national Picasso, Paris

Related posts

More from around the web on the Estrogen Dilemma

  • Patricia Allen, MD reminds us that this article is a personal essay, and that HRT is not the holy grail
  • Dr Mintz advises to read the article with caution

11 Responses to The Estrogen Dilemma – Hope, Hype or Just One Woman’s Story?

  1. I would like to add an interesting observation by T. Colin Campbell, author of "The China Study." In societies that are not accustomed to eating processed food, sugar, and meats like us in the West, women (mostly vegetarian in these societies) go through menopause for the most part without any symptoms. It is a graceful transition. Many of our Western diseases are due to our highly processed, acidic diets. The same is true for osteoporosis, which was found to barely exist in the parts of rural China that were studied. Maybe menopause with hot flashes is not a disease/diagnosis, but merely a symptom of our Western lifestyle.

  2. Hmm. My diet is pretty low in processed everything and not much meat or sugar, more from choice than anything else. However, if I don't take my HRT I don't sleep, which leads to crankiness, sleep deprivation (possibly a patient safetey issue) and achy joints. I did switch to topical which may or may not be less problematic depending on who you read. No intention of giving it up until someone pries it out of my hot sweaty little hands.

  3. The fact that the Gorney article sparked such interest shows us that menopause and symptoms are of huge concern to midlife women.

    I disagree with you that the issue is depression and should be treated with antidepressants. If a woman suffers from depression and needs medication..yes..use an SSRI. But menopausal symptoms are different than depression. The foggy brain, aching joints,mood swings and sleep deprivation from hot flashes are easily treated with estrogen. Certainly the risks from estrogen must be weighed and discussed but substituting an SSRI instead is going after the wrong physiologic cause.

    I know you didn't say that but the SSRIs are being promoted to be used instead of HRT.

    I think there is too much fear about HRT. It takes a long time to individualize treatment for the woman and dose changes are needed but the instant relief of symptoms is rewarding.

  4. Toni –

    Thanks for your thoughtful comments. Don't get me wrong – I presribe HRT for many reasons,including all those you listed. But when someone is suicidal, as the author of the aricle described herself, I would never use HRT alone. I also have a number of patients having both hot flashes and mood issues, with mood predominating, and when given a choice between hrt and SSRI's choose the latter because they do not wish to take any risks of breast cancer. SSRI's can temper hot flashes, although not as well as estrogen does.

    I think the important thing is to let women know the treatment options available to them, as well as encouraging lifestyle changes when needed, and let them decide what treatment they want (or don;t want). For some women, especially those with a family history, the breast cancer concerns trump all else. For others, such as the woman quoted in the article, breast cancer is not a concern. It's all about individualizing care.

    Anon – sounds like you're happy with what you are doing. Good for you!

    Pedro, MD – Interesting. I have read, however, that Chinese women complain of a different set of symptoms – more upper back and shoulder pain that hot flashes. But I am all for a lifestyle that avoids process foods and includes exercise. Thanks for your comments.

  5. I enjoyed the Gorney article in The Times magazine, and your blog. It prompted me to read through the recent North American Menopause Society's position statement (2010), which I think reviewed the recent data in a sensible manner:
    I think there is some validity to the "window hypothesis." In addition, I find it interesting that transdermal HRT may be a safer approach, and has biochemical effects that distinguish it from the oral therapy looked at in the Women's Health Initiative. Obviously more study is needed. Less is more, but it could be that a little, for a short period of time beginning at menopause, is better than none.

  6. I was part of the WHI group meeting in Newark, NJ, starting a bit after I was 50. I chose not to take Premarin for several reasons. Two of my mother's sisters had breast cancer, although my mother did not; I have several benign lumps removed; Then there was the case of how Premarin is manufactured, was too obscene to me… mares impregnated and then hobbled for months…ugh. That said, I hated all the daytime sweats, sleepless nights (still have those years and years after) crazy leg movements, etc., so I tried everything else and in reality nothing much worked. Still the over-riding threat was breast cancer. So I just plowed through.

  7. my comment the other day got lost — darn you, blogger! — but i was also very interested in the NYT article, being peri-menopausal. dr.dialog, i'll go back and look at your link. as a lay person, i just do not see a whole lot about menopause in daily life and accessible reading material.

    i have never favored hormonal interventions, even BC pills, but my doc would not prescribe them anyway, with my sister's aggressive breast cancer diagnosis. it was never an issue at all until my hot flashes pumped into complete overdrive a year or so ago — holy mother of dog, i was waking up on fire up to 10 times a night. my trusted friends and colleagues all said, "you have to get the patch!" this has apparently worked for a lot of them.

    and i didn't, and in fact couldn't. i'm so relieved that my body's back to a few occasional flashes, nothing dire, because at the time it was hard to imagine getting through the next day and night, much less months or years. no, i wasn't suicidal, but it's a little weird to try sleeping with a blue ice pack, no? and 2-4 hours patched together between fanning myself doesn't really cut it for serious work. not at my age, anyway.

  8. Dr Dialogue –

    There indeed may be validity in the window hypothesis. The key word there is "may" . Until we have more data, it is just a hypothesis. As for a little HRT around perimenopause being better than none, that varies from woman to woman. The data on transdermal are compelling to me in that clotting factors seem to be less impacted – although if that will translate to lower clot and stroke risks of course remains to be seen, I think we have a firmer leg to stand on in this regard than the alzheimers hope. Thanks for your comments.

    msdworks –
    As much as folks hate the pregnant mare scenario, I've yet to see any proof that premarin is any worse or better than other estrogens in terms of risks. That said, there are so many other options available that I rarely prescribe it these days. There are a few women for whom it has seemed to work best, probably becuause many of its metabolites are also active estrogens, and they were hyper-metabolizers of bioidentical estrogen (just my own theory…)

    Just goes to show how every woman has her own approach to life and to menopause. Unless major health advantages are proven for hrt, I see no reason to push it at every woman. Nor would i deny it to a woman with a family history of breast cancer if she had good reasons for wnting to take it.

    See my 10 commandments of prescribing HRT if you want to know my overall take on hrt, which has not changes much since the WHI.

    Thanks all for reading and for your thoughtful comments!

  9. As a 50 year old with POF who is starting to try to get off HRT, it's important to me as well. Most of my friends still have their natural periods and just starting to get delays.

    For those of us with POF the whole thing is complicated by our much higher risk of osteoporosis even with HRT that we got for many years already. Our heart disease risk is higher as well. Our breast cancer risk would've been lower but supposedly our years on HRT made it approximately the same. The years we were on HRT makes our hormone exposure similar to that of "normal" women, but is it really similar? Most of us got lower-than-full-replacement doses; I got usual HRT does (which is about half of full replacement) since I was 38; and probably had insufficient natural hormones since the first appearance of symptoms at 32.

    As I am trying to get off HRT (I now reduced it to 1/2 of .375 patch), I keep wondering. Shall I stop? Shall I stay on it longer? I've read every research there is, but it's just so inconclusive, and there is next-to-nothing for women like me. Nobody seems to care about POF when studying HRT. On the one hand the breast cancer fear makes me want to get off of it soon, on the other hand, there is always fear of osteoporosis. Everything has risks including other drugs. Oh well, I guess any decision in life has its risks.

  10. bleep estrogen. had enough fun with THAT over my long life. what i miss is androgen. but what do i know? i just decided to take menopause cold turkey and see what happened. my blessed PA prescribed high-dosage vitamin D this past year, and i feel like a kid again, sort of–to feel really kidlike i'd have to quit my glass of vodka every night. no way.

  11. Dear Cynthia:

    I just read your 2010 article The Estrogen Dilemma. Thank God for you I do. I just started the bio identical hormone patch two weeks ago. I’m a 13 year breast cancer survivor, a famous one here in Vegas. I ran with the patch! Risks and all.

    I was getting so sick a year ago. My husband and I thought I either had breast cancer again (I lost both of them in a double mastectomy on January 17, 2001) or developing a mental illness. We were both scared.

    Finally this March 2014 I ended up I the hospital with the doctors thinking I had a TIA mini stroke. It was not. It was a horrible hormone imbalance. It has been hell. But I am happy that I ended up in emergency babbling gibberish like a stroke victim. All the MRIs, CT scan, ultrasound on my chest and EEG to my brain and every other test they could think of for stroke and cancer came back clean. Thank God!

    I ran to my own primary care doctor a week later and ordered her to test me for my hormones. I passed with flying colors. My FSH was high and my estrogen was low. I had been body-snatched by the menomonster. It was horror moan time for me. It was hell. Until I ran to my OBGYN the same one who had done my hysterectomy (but left my ovaries) just a month before my chest was whacked off. I had lost track with him due to insurance change and now once again found myself in his office because my insurance included him. He was thrilled to see me. Even letting me cry on him in his arms to release the monster within. I was not crazy or cancer cell consumed. I cried and laughed through my tears of relief.

    And yes I begged for the Bio patch. After all he left my ovaries in for 13 some years and they were making more estrogen than the highest patch dose offered. I got the mid-grade 89 octane dose after one week of being on the 87 regular which wasn’t enough.

    I’m only two weeks on the patch but OMG do I feel like me again until the end of the 3rd day before I change the patch out. The roller coaster ride is a bitch I just can’t say it nice but I’m not scared of breast cancer being on it.

    We discussed the risk of BC and will worry about if it ever arrives again. I doubt it. I eat healthy. He put me on for only 2 years. You can study me if you like. I also take Schizandra (I’ve been on it for 13 years for chemo fatigue which it removed and I never went off it then found out last week in Asia that this adaptogen is giving to menopause women all over Asia), Ashawagandha, Maca Root and a few others. They help tremendously alongside the Bios.

    Please feel free to contact me. My full story is at www(dot)AREALLIVEPINKBAT(dot)COM it’s about my breast cancer and baseball career with the men. You’ll love it.

    My cell is 702.234.1581



    I’m also in culinary school and my mantra right now is NOT THROWING KNIVES and maybe I should write a book that title about this menomonster journey. I have a blog www(dot)AuntWeeniesKitchenKoup(dot)WordPress(dot)com I am working on my professional certification so I can help other cancer survivors to make healthy food choices. We don’t learn about good nutrition after cancer. I’ve lost five dragon boat racing breast cancer teammates to BC again three whom ate horrible junk.

    Big hugs from Norine V. aka A Real Live Pink Bat

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.