FDA NEWS
FOR IMMEDIATE RELEASE PO3-01 January 8, 2003 
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FDA Approves New Labels for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Following Review of Women's Health Initiative Data
 

The Food and Drug Administration (FDA) today is advising women and health care professionals about important new safety changes to labeling of all estrogen and estrogen with progestin products for use by postmenopausal women.  These changes reflect FDA's analysis of data from the Women's Health Initiative study (WHI), a landmark study sponsored by the National Institutes of Health that raised concern about risks of using these products.

FDA's labeling revisions are part of a series of actions to provide risk management information to women and advice to health care providers who prescribe these estrogen and estrogen with progestin-containing drug products for postmenopausal women.  FDA will also be issuing updated guidances for manufacturers of estrogen and estrogen with progestin products regarding labeling of those products and development of new products for use in postmenopausal women.  FDA's new labeling changes include a new boxed warning that reflects new risk information and changes to the approved indications to emphasize individualized decisions that appropriately balance the benefits and the potential risks of these products.
 

Dec 1, 2002

This page, as well as several other hormone-oriented ones on this site, is virtually outdated, attitudes to Menopausal Hormone Therapy (in itself a significant change of name - note the abandonment of the term "Replacement") having undergone a major shift over the last few months. However, the page remains here as a record of earlier attitudes, as well as evidence against repeated claims that the WHI (E and P arm) results were a  "bombshell" and "unexpected." For more detail see the WHI page

By now, most major medical organizations have reviewed their recommendations about combination menopausal hormonal therapy and there is little to differentiate them. In general they say:

While treatment for hot flashes and other perimenopausal symptoms remains an option, a woman should be carefully counselled about the risks involved and an individual assessment made of her personal situation. Caution should be exercised about prolonged use.

Routine use of such therapy for the prevention of chronic postmenopausal conditions is not recommended;

Its use for both primary and secondary prevention of cardivascular disease is contraindicated i.e. it should definitely not be used either before or after the development of such conditions.

Its use only for the prevention of osteoporosis should be carefully weighed against its risks, and alternative therapies such as bisphosphonates considered.

 

Until (if ever) there is evidence to the contrary, the assumption must be made that other formulations and dosages of estrogen and progestin carry the same risks as the specific ones in the study.

There is insufficient evidence as yet to decide for or against the use of unopposed estrogen as a preventive measure.

There is insufficient evidence as to whether or not phytoestrogens are protective against osteoporosis or cardiovascular disease. Many of them also list the  various herbs and supplements which are used for perimenopausal symptoms, while failing to point out that there is little or no evidence that they 'work'.

April 16, 2002: Evidence of a sea change in attitude to HRT finally approaching the US can be read in an article in the Journal of the American Medical Association at http://jama.ama-assn.org/issues/v287n15/ffull/jmn0417-1.html
Hormone Replacement Therapy Falls Out of Favor With Expert Committee
Brian Vastag
[Introduction only]
Bethesda, Md

Falling in line with the evidence-based medicine trend, an international team of women's health experts is discouraging the use of hormone replacement therapy (HRT) for many postmenopausal conditions.  Coronary heart disease, fractures, depression, urinary incontinenceall cited in the past as prime reasons to initiate HRTare losing favor as valid indications for it, as evidence from high-quality clinical trials accumulates.

In 1992, three major organizations threw their collective weight behind guidelines that pushed physicians to prescribe HRT for women with or at risk of heart disease and osteoporosis.  Endorsed by the American College of Physicians, the American College of Family Medicine, and the US Preventive Services Task Force, the guidelines relied almost exclusively on soft data from observational studies and clinical experience.

---

......Unfortunately, many of these beneficial effects of estrogen were accepted without the hard evidence that is now required from other medications.....

If you are reading this, it's likely you are considering the use of hormonal drugs (and make no mistake - they are drugs) either in the short term to combat symptoms or in the long term for their promised preventative properties. 

If you are like most of the women posting to such internet forums as alt.support.menopause, you have read the ubiquitous ads, talked to other women and/or been told by your doctor that s/he is going to "put you on" HRT, but are not entirely convinced by what you've read or been told. Those who were, are already taking them without question.

Before you make the decision about hormone use for any of the following typical reasons, read the links provided so that you may have a fuller picture of the situation - untainted by commercial interests.

• You are "that age." As the sole reason, this is totally unacceptable from a doctor and the mark of an assembly line attitude. It is probably influenced by the premises that
• "Women never used to live beyond menopause" and
• "You have lived longer than Mother Nature intended."
• "Menopause is an estrogen deficiency disease", and maybe also
• Your FSH test shows you are "in menopause" or "menopausal"
• You have "menopausal symptoms", such as hot flashes or vaginal dryness which are the only FDA approved uses for symptoms. While relief is usually presented as a sure thing, it isn't always and not infrequently causes worse problems.
• You have heavy bleeding. N.B. Typically, hormone use for this is progestin only. Estrogen can make matters worse.
• "For your bones"
• "For your heart" This is an off label use which has been in operation for so long that it appears to be an established fact, despite being specifically disclaimed in the FDA patient leaflet. In August 2001, the American Heart Association recommended against estrogen use for secondary prevention of heart disease. On July 9, 2002 this recommendation was widened to exclude combination HRT (estrogen+ progestin) from any use for heart disease prevention.
• For your brain
• For your skin and general "youthfulness" - the FDA patient info leaflet specifically disclaims this too. It is a reason which is usually unspoken and an expectation driven primarily by skillful marketing, especially by "super models" such as Lauren Hutton who enthuses about "her" estrogen, while never mentioning that she is paid to promote it. As a private individual she cannot be sued for malpractice or false advertising as she is only telling us what she thinks...

Next, examine the risks
On the whole, the risks of hormone therapy are downplayed with the theory going that the claimed benefits outweigh them but with the benefits looking ever more doubtful, the risk benefit ratio is worsening. It is important to differentiate between time limited OHT use to mitigate intractable perimenopausal symptoms and its ongoing lifelong use for a hoped for risk reduction (*not* prevention) of heart disease and osteoporosis. In the first case, it is quickly apparent whether it "works" and if it doesn't then it is abandoned - as it is if the short term side effects are worse than the original complaint. On the other hand any benefits to be expected from long term use must be taken on faith and benefits can never be proven - maybe the woman hadn't been at risk in the first place! Yet for these putative benefits, women are being asked to *add* a known risk of cancer - which however slight is avoidable.

Short term "minor risks" which women know about, but officialdom disregards.

• It not only doesn't work but causes worse symptoms.
• It doesn't work and you're out a lot of money.
• It does work but causes other symptoms, so you either quit or have to go on more drugs to counteract the effect of the first....and so on....;-)
• Even though you quit, the symptoms it caused don't go away for a long time.
• Quitting is itself a problem.

• A "slight" increased risk of breast cancer
• Increased risk of endometrial cancer in women with a uterus - mitigated by the addition of progestin, which is now being suspected to further increase the risk of breast cancer.
• Increased risk of gall bladder disease.
• Increased risk of deep vein thrombosis (clotting).
• A whole slew of other side effects, many of which are symptoms that the drugs are being prescribed for! The link provided is for Prempro, but the warnings are essentially the same for all formulations, including "natural" hormones.
• and now, new in Feb 2002, the risk of worsened quality of life for those postmenopausal women without hot flashes.

Recently (May 2001) a woman claiming to be doing market research precipitated a number of responses from alt.support.menopause which indicated personal doubt about universal need for HRT, including a poem in the style of Dr Seuss entitled Do You Like the HRT?

Responses to a further query as to what people didn't like about HRT included: 

My main objection is that when we reach "a certain age" we're none-too-gently pushed toward taking it in some form or another whether we have any severe symptoms or not, not because it's good for us (because it certainly isn't) but because you want to make another dollar or two and you've convinced a whole bunch of doctors to agree with you.  I object to the fact that, while it's been listed as a carcinogen the pharmaceutical companies try to minimize (or hide) that fact, and urge women to get on it and stay on it for years - in spite of the fact that long term use iss not recommended by some of the more knowledgeable persons in the medical profession. Add to that the fact that simple weight-bearing exercise and a good diet are far more effective in fighting osteoporosis.   I don't believe we necessarily need to be medicated/drugged through a perfectly normal phase of life.  And I -certainly- wouldn't take the word of a paid spokesperson (Lauren Hutton) who makes it sound as if she's done tons of research in the matter, and probably hasn't read one single reliable study about the ill effects of HRT.  As I have said here before, I could bitch slap the gap right out of her teeth whenever I see her (which seems to be more and more often, lately, telling us we're all living in *denial*).

If HRT were that good, you wouldn't need to advertise, you wouldn't need a spokesperson, you wouldn't need to come up with asinine ideas for making a patch more attractive.

How old are you, A?  Have you read the studies?  Or were you just hired to look into this?  I challenge you to peruse the web sites mentioned frequently here, read the studies--not the news stories that "spin" the message-- and figure out for yourself why so many of us here (though not all) are not exactly jumping for joy over HRT.
Marilee

Then again, I have actually come close to trying HRT a couple of times, when I've felt *really* crummy hormone-wise, to see if it would work as a short-term help (*not* lifetime use).  But then I feel better again & any thoughts I had of trying HRT go away, rather abruptly. ;-)
Cathy

I can't speak for anyone else, but I'm in the middle group, leaning toward the latter, as more and more research emerges indicating that these drugs have been "hard-sold" to American women through campaigns of overstatement and, in some instances, downright misstatement about their effects (and side effects). 

I personally object to the treatment of menopause - a normal stage of life every woman will go through if she lives long enough - as a deficiency disease that requires us to take hormones our bodies aren't designed to need in such high quantities once we are no longer of reproductive age. And I object even more to the corporate efforts to sell us on these drugs as magic fountains of youth that will supposedly keep us dewy-skinned, firm-bosomed, and "feminine" forever. I object to the part of our culture that equates my femininity with the few body parts that were meant for reproduction, and implies that if I'm no longer fertile, I'm no longer a woman. I object to the soft-pedaling of the very real risks these drugs pose for women with propensities toward certain types of cancer. I object to these corporations hiring wealthy models and movie stars to try to con us into thinking that if we just take a little estrogen, we'll be just as rich and famous and "beautiful" as they think they are.

The production and sale of hormone drugs to women is a *huge* profit center for the pharmas. I understand why they don't want to lose it, but I loathe their attitude, their politics and their use of deception to make money for their stock-holders.

I appreciate your willingness to carry our comments to the people who employ you, but I don't think for a minute that mine will have the slightest effect on the way they do business.
Pat K

Later, when you are in the mood for an anthropological look at menopause which includes the question of HRT, try the long thesis entitled Rejecting Disease and Constructing Experience: Menopausal Women's Resistance to Medical Hegemony. Despite the academic title, the content is readable and interesting.

The soapbox archives contain numerous opinion pieces on the topic.

A good question, for a variety of reasons. First, the medical model suggests that 80% of women experience so called menopausal complaints. But, in North America, fewer than 15% of women actually participate in any form of HRT. This suggests that a very large majority of women do quite well without the hormonal intervention, and draws into question the relevance of a figure like 80%. Having said this, there is no question that the experience for some is very difficult indeed. Medicine is going to have something of a biased view here for the simple reason that they are going to see the women with the worst experience. 

It really is amazing that so little information exists on this issue, particularly when the medical model is approaching a recommendation that HRT be offered to all menopausal women based on putative benefits in cardiovascular and skeletal risk. 

In any risk management strategy the quality of life of the participants is crucial. If you feel worse you are less likely to stay with the intervention. And, keep in mind, the benefits will accrue to only a few. 

There is a common perception that HRT has salutary effects on the quality of life. This perception is misplaced. In fact, very little Q.O.L. data is available for the intervention. What is available is generally positive. However, it applies only to those women who have sought treatment - in other words, those who are having the worst experience. 

And of those 15% who are treated, 80% have discontinued the intervention by the end of year three. This is open to interpretation. The medical model will say that they did not fully understand the benefit. On the other hand, it does question what the nature of the benefit was. If the intervention was so wonderful, or offered ongoing benefit in terms of Q.O.L., surely those who break from therapy would quickly get themselves back on. This tends not to happen. 

Back to the original question. To what extent does hormonal status determine Quality of Life? 

In one of the few reports I have seen to address this issue, Maturitas 8 (1986) p.217-228 "Relationships between psychological symptoms, somatic complaints and menopausal status", Hunter et.al. found that somatic (physical) and psychological symptoms were best predicted by social class and a "state of being employed", while vasomotor symptoms and sexual difficulty were better predicted by menopausal status.

Risk issues aside, this is a pretty limited spectrum of benefit. 

Far as I know, hormones won't get you a job. But having a job may allow you to get the hormones. 

In this report, vasomotor symptoms were reported by 55% of women. This is substantially less than the 80% figure so often tossed about. 

So, HRT hardly seems to be the ready remedy for all that ails ya. And women, judged by their participation, seem to understand this. 

As for the future, I would argue that before the menopause is transformed into an "obligate endocrinopathy" to be treated, we ought to better try and understand who will benefit (stratification of risk), when they will benefit (timing and duration of the intervention), and how they will benefit (end points including Quality of Life). After all, it aint candy. 

Mark ([email protected])

        Perimenopause is self-limiting. It does not last forever and will go away on its own as it is only a transitional stage from being hormonally reproductive to being hormonally non-reproductive. 

        The transition of menopause is often described as puberty in reverse and puberty did not last forever. Pre-puberty, girls were not estrogen or progesterone "deficient." Their bones were not crumbling and they were not at risk for heart disease due to their lack of progesterone and estrogen. Nor was it recommended they intervene with the puberty process with powerful hormone drugs to subvert the bodies normal, albeit disruptive, puberty programming. 

        These two hormones (estrogen and progesterone) are produced in excessive amounts during the reproductive years to sustain the highly specialized task of reproduction.  When this biological reproductive demand has ceased at menopause, these hormones adjust back to their normal levels.  Unless a woman has been abruptly castrated, there is no reason to universally "replace" these hormones at their former reproductive levels.  They served their specialized purpose and are now quiescent at much lower levels again. 

        (Peri)Menopause does not last forever. Typically the peri-menopause zone can last 7-10 years in varying degrees of intensity. But it does end at some fuzzy point in time, much as it begins at some fuzzy point in time, with its fairly predictable cluster of signs.  Again, just like puberty - with all of its individual variations and variable beginning and ending points.

        So eight years is not an unusual time to be dealing with transitional menopause signs and it may well have ended for A after this period of time regardless of her choice of drug regimen. Menopause  is an ancient and biologically adaptive process that has a million year old evolutionary history. 

        No one can really say what will happen in the long run from chemically interfering with this process. So far there has only been a  40 year history of doing this so the whole attempt to intervene in this area is still in the realm of mass experimentation. 

        The precautions A. and her doctor recommend need to be set forth in more detail if one chooses to take hormone drugs during this transition time. These drugs can have a deleterious effect on the breast, uterus, blood lipids and gall bladder, as well as creating diabetic instability, risk of stroke and melanoma. (Read the FDA product insert  warnings.) 

        Annual medical concerns when taking these drugs need at a minimum to include the following: 

        1. Mammogram 
        2. Uterine biopsy (not just a Pap exam) if estrogen alone is taken
        3. Blood chemistry for circulating hormone levels 
        4. Blood lipids analysis 
        5. Pap exam 
        6. Blood pressure check

        The annual costs of hormone drugs themselves run from $20-$40 US a  month along with the several hundred dollars of necessary extra annual  tests. The efficacy of these tests as routine annual exams for the  well-woman who is not taking these drugs has not been established so  these are not necessarily typical annual expenses for a non-drug taking well-woman. 

        Many of the alleged over-age-50 risk factors for women have been  established by examining the risk factors found in the generation of women who were 60% castrated and who made Premarin (estrogen) America's leading selling drug. Consequently, it is presently unknown what the true risk  factors are for women who avoid these drugs and are not surgically at risk. 

        Additional hormone drug risk factors include being over weight,  smoking and alcohol consumption. Over 3 alcoholic drinks a week increases one's health risks when combined with use of hormone drugs.

1. Lack of specificity as to meno drugs or meno status
2. Multiple threats if one does not take hormone drugs
3. Failure to state known risks and side effects of hormone drugs
4. Name calling and illusions of drug induced eternal youth and beauty

 No problem. Many women make this choice for themselves. After all Premarin (estrogen drug) has been a leading selling drug in America for many years. But let's look beyond this poster's personal testimony for the facts she attempts to present to this support group of partners' looking for menopause information. 

 Number one: we do not know the meno status of this woman. Has she finished menopause, has she just started menopause, what were her symptoms, did she have a surgical menopause, how long has she been taking these drugs and which specific drugs is she taking. 

Women who have had a surgical castration throwing them immediately into menopause get a very different type of drug relief from estrogen drugs than do those who have not been castrated and who need to prevent the uterine cancers caused by the estrogen drugs. These are totally different experiences. 

 So to educate yourself when you see these general drug "enthusiasm" posts, be sure to ask what hormone drug and for what type of menopause? You will get very different answers as there are well over 20 different combinations of drugs and surgical statuses. Be sure to know what exactly the poster is referring to when drugs are recommended. 

 Number two: This type of pro-drug post typically includes multiple threats if you do not take these unspecified drugs. In this case we have threats of heart disease, osteoporosis, Alzheimers, marital discord and adultery. Put these threats through the common sense test. Can one drug or a combination of drugs give this much benefit to one's life? This poster is claiming that in fact one family of drugs can. Yet she fails to be specific about which particular drug(s) and only uses the term "hormones" generically as if it were some sort of "majik" pill. 

 These threats are out dated and apply more typically to the castrated woman who is surgically placed at risk for more problems than a woman who goes through the menopause transition naturally and without needing to distort her body chemistry with drugs. 

 Number three: Risks and side effects are minimized or ignored. Again since this poster has failed to state what exact drugs she is taking, it is hard to evaluate the potential risks and side effects. But clearly she is stating there are few to none. This is not true as the evidence is building about breast cancer according to the recent Scientific American risk analysis for estrogen. Nothing is really known about the effects of the addition of progestins to this hormone formula. [2000 - now some evidence it adds to the risk] And the very -first- adequate, long term, double blind studies on these products are just now getting underway with results not being due until the year 2005. 

 It is entirely misleading and dangerous, when the largest drug taking population of American woman are dying now at unenviable rates according to WHO statistics compared to just 10 years ago, to say that these drugs have no risk and are proving every day to be better than expected. Just the opposite is true. They are showing everyday to have been over-sold, ineffective for putative "benefits" and seriously implicated in the growth of serious female health problems, breast cancer in particular. 

 Number four: These pro-drug posters never seem to finish a post without name calling. Here we have anyone who present countering information being labeled as an "old fashioned granny" old before her time, unable to please a man, dried up, haggard, undesirable, betrayed." This does not sound like any drug free woman that I know. 

 So there you have it. Standard pro-drug format. 

1. Lack of specificity of meno drugs or meno status
2. Multiple threats if one does not take hormone drugs
3. Failure to state known hormone drug taking risks and side effects
4. Name calling and illusions of drug induced eternal youth and beauty.

        Within this 2 year period she said she started getting headaches, achy joints, started bleeding all the time, gained weight, felt tired and depressed and had breasts that hurt so bad she could not run the shower water across her front. The only benefit she noticed was less wispy facial hair. 

        She and her doctor kept trying to adjust her dose until she finally decided to quit entirely. The irony being that she felt fine and then only -after- taking the HRT, did she get many of the very same symptoms that many women report getting -before- taking HRT.  Odd. 

Joan L. 

There are women who, when faced with a family history of Alzheimer's, say "even if all the research isn't in,  if there's a chance it will keep me from getting this horrible disease, I'm taking estrogen". That's their right. 

There are women who opt for estrogen but who are made absolutely sick and miserable by provera. They do not have to take provera. Yep, they up their risk for endometrial cancer by not taking it -- but it is their RIGHT, their decision.  I just want it to be informed. I want them to know that there are ways to make that decision as safe as it can be (getting regular endometrial biopsies, for example, or trying natural micronized progesterone). 

In thirty years, maybe medical science will have come up with some clear cut answers for risks and benefits of HRT and ERT; many are well hinted at but not defined.....  but women should not be bullied into taking HRT , and they should not be bullied into not taking HRT. 

Women are individuals. They need to feel their power, make their own decisions. 

Much as some would like to say they have all the answers, no one has all the answers. The only one that can decide for a woman is the individual woman herself 
Sher

Kathryn:
 I would also be interested in what Shelly has to say to this. I have my own ideas of course, this is one of those issues we do have to decide for ourselves, there is no right or wrong answer known as yet.

Terri
Snyderman is firmly in the pro-hormone camp. She also promulgates the falsehood that in previous generation women didn't survive menopause so didn't "need" hormones. I have heard her say exactly that on many NBC "Today" segments. I don't know if it's in her book or not. 

There is clearly a split in the medical community about the overall benefits of hormones for the prevention of heart disease. In the Dr Suzuki television show ( The Nature of Things) I saw last week, Dr. Graham Colditz from Harvard Medical School, (who is involved in the Nurses studies), made the point that there are many other options that you can take to prevent heart disease other than taking hormones. He also mentioned that in the process of marketing hormone replacement, the [drug industry ? my notes are not clear] may be under representing the risks of taking hormones.

Your reference to Colditz is a very interesting one. He is the lead author of the most authoritative studies (the various papers on the Nurse's Study) on the cardiac benefits of hormones. If he is now questioning the validity of the risk/benefit conclusions of those studies and the role of "marketing" in promoting those alleged benefits, I think everyone should sit up and take notice. 
Terri

Dr. Issac Schiff from Massachusetts General Hospital and also on the Harvard Women's Health Watch Advisory Board for Gynecology says he has an open mind at the moment about the benefits of hormones for preventing heart disease. He stated that the biological relationship of estrogen to heart disease in not yet understood or researched. "We have to be very careful" he said, "how we interpret studies". He went on to say that women have a lower mortality for virtually everything over men, (except breast and uterine cancer), and that though after menopause women begin to gain on men on mortality from heart disease they do not even approach men until advanced age and never pass the rate of disease for men at any age..

 As I stated, my gut feeling, after extensively reading about the pros/cons, has kept me from going on HRT. I probably will not go on HRT, unless my symptoms worsen.  I will exercise, eat healthy and take supplements /herbs instead. But I do worry about HD and Alzheimer's. It's going to be a long wait for the year 2005 - hopefully I won't have a heart attack before then! Thanks for your response. 

The way time seems to be flying I think it will be 2005 pretty darn fast <grin> The odds of heart disease or Alzheimers before then are quite slim G. Besides the way scientists are flip flopping about eating things like eggs and butter, who knows what we will be worrying about by then.

 Kathryn