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David Katz, M.D.

David Katz, M.D.

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Hormone-Replacement Follies: A Brief History

Posted: 04/13/11 08:23 AM ET

Once upon a time, the first human woman outlived the biological limits of her ovarian hormone production, and menopause was born. None can give the date for this event, but we can be confident it was a very, very, very long time ago.

Medical menopause, however, was born much more recently. For this, we can give a date -- situated in the early 1940s when the FDA approved estrogen replacement for the treatment of menopause and its related symptoms.

We like to believe that necessity is the mother of invention, and indeed it may often be so. But Jared Diamond shrewdly pointed out that as often at least, invention is the mother of necessity. When we invented medical menopause, the necessity of treatments that ensued grew into a multi-billion-dollar industry. The invention of that industry propagated more necessity. For a span of decades, science fostered this trend with observational studies suggesting the many benefits of hormone replacement.

The practice that came to prevail, even though many true authorities on the topic were dubious all the while, was the use of Prem/Pro, a combination of Premarin (conjugated equine estrogen, or, to spell it right out: estrogen derived from the urine of pregnant female horses), and Provera (medroxyprogesterone acetate, a synthetic progesterone many times more potent in its action than the native human variety).

The popular view for those recent decades, propagated in all the ways we might imagine by both our limited knowledge, and large sums of money changing hands, was that hormone replacement was good, and that Prem/Pro was good hormone replacement.

I hasten to add that the alternative to "good" need not be bad. A good alternative to good is "good on occasion," or "good for some." I am by no means suggesting that hormone replacement therapy is a bad idea, or wrong for all women. It can clearly be very important at times. I am simply pointing out that we tended, over the last half century, to be entirely in love, or entirely out of love with the concept as a society, and as a medical community.

One of the dominant themes in modern medicine is "evidence-based" practice. As attention, over the past 30 years or so, focused more on standards of evidence, misgivings began to arise -- at least as far back as the 1980s -- about the observational data on which enthusiasm for HRT was mostly based. Seeing X and Y happen together in a large group of people does not reliably mean that X is causing Y. It may be that everyone who does X happens to have Z, and Z causes Y. This is a salient limitation of observational research. As an example, people who don't have televisions are more prone to tuberculosis -- but not because TVs prevent TB! Rather, not having a television is proxy for poverty, and poverty in turn is associated with a number of the factors that truly do increase TB risk.

For a while longer, early misgivings about the evidence base for HRT were just small waves on the placid sea of prevailing conviction. Our boat wasn't severely rocked until the HERS trial results were published in 1998. HERS was the first significant randomized, placebo-controlled trial of hormone replacement therapy, and it suggested an overall lack of benefit for cardiovascular disease prevention. Nearly 3,000 were enrolled.

Then, with publication of the Women's Health Initiative (WHI) results in 2002, the boat of consensus opinion was capsized outright. This randomized trial in nearly 20,000 women showed net harm from hormone replacement therapy, and advised directly against the practice.

The latest news is again courtesy of the WHI. In a paper just published in JAMA, the long-term experience of women in the WHI who had undergone a hysterectomy and received only estrogen is reported, and reveals a clear reduction in breast cancer risk. The study is evoking widespread media attention, and some rekindling of that love we had all lost for hormone replacement therapy.

Looking at all this in hindsight, we never had as much cause to love or hate HRT as our behavior during any interval suggested. Our enthusiasm for hormone replacement got well ahead of the data demonstrating net benefit for most women. Then, our renunciation of the practice was far more expansive than the data warranted. Both the HERS and WHI trials used the same kind of hormones, and both enrolled women a long time after menopause.

Studies since suggest that the benefits of hormone replacement appear to be most robust when the practice is applied as soon after menopause as possible. The benefits are greater when women are carefully selected; those with increased risk for blood clots should not participate, for instance. And there are many options -- and most would say many far better options- than Prem/Pro, including other estrogen/progesterone combinations, estrogen alone, bio-identical hormones, and the synthetic estrogen-like drugs such as raloxifene.

There are two take-away messages. The first is that hormone replacement therapy at menopause is not good for all, nor bad for all. It clearly can confer benefit, but it depends how it is done, and for whom. When the right hormone preparations are thoughtfully applied in the right women for the right reasons, I am convinced considerable benefit can come of it. I am equally convinced of the potential for harm when the wrong preparations are thoughtlessly used for the wrong reasons in the wrong women. You and a doctor you can really talk to should sort this out together.

The other message is that science is as it ever was: incremental and evolutionary, rarely revolutionary. Evidence accumulates over time, and the weight of evidence tips toward the truth. When science becomes a teeter-totter of sequentially opposed truths, we have lost our way.

That has been the history to date of hormone replacement therapy: rather half-witted over-reactions to the half-truths that any given trial provided. Those who do not learn from the follies of this history are destined to repeat them. Again.

Dr. David L. Katz; www.davidkatzmd.com

www.turnthetidefoundation.org


PS- for a good source of professional information about hormone replacement options and menopause in general, visit http://www.menopause.org/. I also recommend http://www.menopausemakeover.com/ for a hefty dose of menopause mastery and empowerment.

 

Follow David Katz, M.D. on Twitter: www.twitter.com/DrDavidKatz

Once upon a time, the first human woman outlived the biological limits of her ovarian hormone production, and menopause was born. None can give the date for this event, but we can be confident it was ...
Once upon a time, the first human woman outlived the biological limits of her ovarian hormone production, and menopause was born. None can give the date for this event, but we can be confident it was ...
 
 
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11:06 AM on 04/20/2011
Thank you for your valuable post. We have decided to share it with our global physician audience at PhysicianNexus.com: http://physiciannexus.com/forum/topics/hormonereplacement-follies-a

Jaerou Kim
Team Member
www.PhysicianNexus.com
Physicians Comparing Treatments Worldwide
12:17 AM on 04/14/2011
Nowhere in this article is there any mention of how women feel on hormone replacement.

I am not sure about the last study done, but the others were based on horse urine replacement and the participants were not screened for lifestyle risks.

Now about logic: A woman is considered healthy when she is producing her full and balanced complement of hormones. When she no longer produces the full and balanced complement, it suddenly becomes unhealthy to top them up and balance them out to former healthy levels. That, my friends, is twisted logic; logic gone mad.

There are a few doctors in the US who believe in bio-identical hormone replacement. They have been treating patients for years with no adverse effects. The results are life changing for women.

Before ERT, I was lethargic with a continuous background malaise. My fingers were stiff in the morning, and it was difficult to get out of bed in the morning and get motivated, let alone the embarrassing and awful inner body heat and outer body sweats. The change after ERT (not horse urine) was dramatic and swift: new motivation, regular exercise, responsible job, personal ventures, on and on....

I will be on ERT to my dying days, "risks" and all. I am not about to pay much attention to men who point out the adverse results of studies based on premarin and a bunch of women not screened for lifestyle habits.
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blondebeblonde
Blondes also prefer gentlemen
05:29 PM on 06/03/2011
Though this post of yours is two months old, I was following other articles by Dr. Katz, clicked on this article then saw your post. As I was reading his article, I was thinking much of what you articulated. I was also thinking, "Great, another man, albeit a doctor, has an opinion about this."

I hit menopause in my late 30s. I am on HRT and I find that in addition to all the wonderful properties of HRT that you mentioned, my skin is more supple and I maintain shape and muscle more easily. I went off of HRT for two years upon the recommendation of my then ob/gyn, and I felt terrible. Going back on HRT, I was more aware of all the pluses.

I especially love your last sentence: "I am not about to pay much attention to men who point out the adverse results of studies based on premarin and a bunch of women not screened for lifestyle habits."

I, too, will take HRT until my dying day. I want to go through every day of my life--however long that may be--feeling great, not miserable.

I checked out some of your other posts and find I agree with you on many things you have to say...so, FANNED!
07:16 PM on 04/13/2011
The sad thing is that even this well-intentioned physician's discussion is driven by Big Pharma ... a reasonable, logical, superior alternative to PremPro or Estrace are Bio-identical hormones. NOT patent-worthy approximations of female hormones, but the female hormones themselves. Not patentable (not sufficiently lucrative) but identical to the hormones women enjoy before menopause and can benefit from after menopause. The smaller studies done to date and documented in Holtorf's Postgraduate Medicine article in January 2009 indicate that bio-identical hormones reduce the risks of all the disease of post-menopausal women. WHy isn't that more widely known? Not supported by Big Pharma... :(
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RMankovitz
Researcher, inventor, entrepreneur, author
04:47 PM on 04/13/2011
Regarding menopause issues, in addition to women that may benefit from HRT, and those who may not, there is a third group – those who don’t need it in the first place.

Could there be women that go through menopause, including hormone changes, without any adverse symptoms? You bet. If you ask a doc why you have symptoms and your friend does not, they are likely to say something like genetics, which is bumperspeak for “I don’t have a clue.” Did you know that there is no word in the Japanese language for “hot flashes.”

My point is that formal studies should be conducted on this issue to see if there is an environmental component to the adverse symptoms. Who would fund these studies? Nobody, because there is no money in primary prevention.

There were a few informal studies in the past on Mayan populations that seemed to indicate environmental influences, including diet. A discussion and references can be found in “The Wellness Project,” along with an experimental eating plan designed by nature to promote wellness.

Roy Mankovitz, Director
http://www.MontecitoWellness.com
A research organization
12:20 AM on 04/14/2011
There you go again.

These posts are not for spamming one's own ventures -- with, in my view, questionable credentials for the particular topics.
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RMankovitz
Researcher, inventor, entrepreneur, author
02:19 AM on 04/14/2011
Thanks for sharing your personal opinion, and for being such an avid reader of my comments.

Since you have offered no personal credentials on any topic, apparently have no ventures that contribute to the human condition, criticize research you have never read, and prefer to comment on the messenger rather than on the message, I will give your opinion the weight it deserves.

If you do not like my comments, do not read them. In the future, I will endeavor to do the same for yours.
03:50 PM on 04/13/2011
Most women can't go to their doctors to sort out HRT decisions, because most doctors do not know, or were never taught, even basic hormone biochemistry. They know how to diagnose and prescribe drugs, and their info comes from the drug companies. I recently received a letter from a woman whose doctor eventually had her on 4 mg of estradiol because the lower doses made her symptoms worse. It is ignorant, irrational and potentially deadly to prescribe that much estrogen to any woman for any reason, but I get letters of that ilk daily. Unless doctors like yourself fight for medical education grounded in knowledge and understanding rather than drug company interests, woman will continue to suffer the consequences. Further, you point out the lack of evidence behind the popularity of PremPro, but then give readers a link to the NAMS website. NAMS is essentially the editorial arm of the maker of PremPro. Is that really a good source of reliable, evidence-based information?
03:42 PM on 04/13/2011
My Grandmother was just diagnosed with ductile carcinoma in her mid 70's. No other health problems before and absolutely no trace of cancer in our family. She did receive hormone replacement therapy after menopause. Thank God she got treated early and all the cancer was removed. I think that link needs to be studied as much as possible.
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thinkingwomanmillstone
I'm nervous. My life is under a Micro-bioscope.
03:24 PM on 04/13/2011
so basically it's a cr@pshoot? There is no way to decide with any degree of certainty. So I have erred on the side of doing nothing because it is far easier to guess that the body knows what's it doing and to undo what it lacks than it is to undo an artificial addition. But, I am not at all sure of that. To me the advice on HRT is almost based on the doctor's philosophy or religion not on any science. It changes on a yearly(if not more frequently) basis. Men would not put up with this nonsense. It once again illustrates the lack of importance women's health has in medical research. I would like my mind back though...tell me how to do that and I'm on board.
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msmanatee
“A hundred years from now? All new people.” AL
05:28 PM on 04/13/2011
I agree. My last nurse practitioner in training wanted to wait for the blood work to see if my symptoms were thyroid related. The nurse practitioner who read the blood work ,results wasn't quite sure what to do. I decided to wait and see as well. And, it is my mind that I miss the most:) (what was I doing again.....)

A friend shared that fish oil worked for her and suggested talking to a good health food store for more options.

As for women's health, I see danger ahead...
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defortier
Editor of Brain Today Blog.
01:44 PM on 04/13/2011
While the topic of this story, "hormone replacement therapy", is quite specific, the theme about public perception of medical science is broad and deeply relevant. As Dr. Katz, notes, a strong commercial incentive can often shape stories in the media. As such, "experts" with impressive credentials can build entire careers advocating for (or against) particular medical approaches.

We are seeing this play out now in the Alzheimer's field. Existing treatments are over-hyped by some while unfairly bashed by others, new diagnostic approaches are hailed as either "major advances" or "ethical nightmares", and the role of an educated public is cast by some in a beneficial light while portrayed as a major source of unrequited angst by others.

Overall, we don't have enough solid science in hand to definitively resolve each of these debates. However, the picture is much more clear than that presented by dueling sources in the popular press. We clarify the daily headlines about brain health at the Brain Today blog: www.BrainToday.com.
12:19 PM on 04/13/2011
Why can't women make up their minds?
12:13 PM on 04/13/2011
I will be 76 Friday. I have been taking Premarin for over 20 years. Once menopause ended, I was still having debilitating hot flashes. Still am to this day without the Premarin. My gyn knows my health history and me very well after 16 years. I am happy to say I am probably one of the healthiest 76 year olds you will ever meet. No health problems, whatsoever. (I walk an hour 4 or 5 days a week. Premarin is the only prescription medication I take or need. I do take one 81 mg asprin and 2 fish oil capsules daily.) BUT, someone will have to wrench it from my cold, dead hands because if I had to endure the hot flashes I get without it, I would rather be under the daisies. All my living friends had taken Premarin to offset the hot flashes and they too are still having hot flashes in their 70s. So, I wonder if the Premarin is the cause as well as the cure for the hot flashes, after menopause has ended. Over the years, my gyn has lowered the dosage to .3mg.
12:02 PM on 04/13/2011
After so much contradictory information, women make their own choices but feel ambivalent.
Real women discuss it at www.ZestNow for women 55 and Forward http://zestnow.com/view/health/9/Worth-the-Risk.html
11:13 AM on 04/13/2011
Since the beginning of time women have had to go through menopause, hot flashes, feeling terrible, etc. All of a sudden it like hundreds of other natural body changes menopause became a disease that needed a pill. Are women so frail they can't handle things like this anymore ?
Or is everyone just so gullible they will buy into anything and everything letting common sense go by the wayside.
Trying to change and alter mother nature will never work out in the long run. She'll always have the upper hand.
Now kids are taking hormones to stop periods. Great only 3 periods / year. Lets see how well that works out.
03:23 PM on 04/13/2011
I had chronic insomnia from the time I became post-menopausal a few years ago until recently when it became so debilitating that I started HRT. I am finally able to sleep at night and function during the day. I am neither frail nor gullible. Nor am I judgmental.
09:02 AM on 04/13/2011
Agreed - but will women (whose doctors seldom have the time to read the chart, if any, before appointments) remember to report that they smoke, or have family members with estrogen-fueled breast cancer, or any of the other risk factors for harm with HRT? Will their doctors, within the confines of the 10 to 15 minute appointment, have the time to ask them?