The Controversy Over Post-Menopausal Estrogen Use

[Time for change]

Background on the controversy

When I went to medical school and Public Health school in the 1970s, the belief among large numbers of public health professionals was that most post-menopausal women should receive hormone replacement therapy (HRT) for the remainder of their life. There were several reasons for this belief. Not only did HRT relieve troublesome and sometimes life-altering post-menopausal symptoms, but it also substantially reduced the risk of osteoporosis with subsequent hip fracture (often a life altering terminal event in older women) and apparently lowered the risk of coronary artery disease, the number one killer of women (as well as men). On the negative side was a slight and inconsistently demonstrated increased risk of breast cancer and a large increase in endometrial cancer. Since the increased risk of breast cancer was small at most, and not well demonstrated, and since endometrial cancer is rare with or without ERT, the overall benefits were considered by many public health professionals to outweigh the risks for most post-menopausal women, though the issue was controversial. Here is a 1999 review of the subject, which summarizes the epidemiological evidence. And here is an article that showed an overall 21% reduction in mortality in women who took ERT, compared to women who did not take it – though the difference was not quite statistically significant at the 95% confidence level.

Then, in 2002 findings were released from the Women’s Health Initiative (WHI), a large randomized clinical trial on the use of ERT in post-menopausal women, sponsored by the National Institutes of Health (NIH). The most surprising finding of this study was that not only did it now appear that HRT did not lower the risk of coronary artery disease, but HRT may actually increase that risk. Consequently, the study was stopped, and the recommendations for the use of HRT in post-menopausal women were radically altered.


Considerations on the use of epidemiological research vs. controlled clinical trials

One reason for the vast turnaround in the recommendations for HRT was the fact that the new WHI study was based on a randomized clinical trial, in contrast to the older evidence which was based on epidemiological research. Randomized clinic trials pose a significant advantage over epidemiological research because, by virtue of the fact that they randomize the treatment, it is generally assured that pre-existing risks will be fairly equal in the treatment group as compared with the control group. With pre-existing risks equalized, the scene is set for a more valid assessment of the treatment. Epidemiological studies, on the other hand, are observational, meaning that treatment is determined by the needs and wishes of the individual subjects, rather than the experimenter. Consequently, there is always the possibility that the two groups may have different pre-existing risks, which may influence their relative outcomes (though efforts are made to statistically control for differences in pre-existing risk).

Though these advantages of randomized clinical trials over epidemiological research are well recognized, there are also advantages that epidemiological studies have over clinical trials, and those advantages are less well recognized. One of the biggest advantages of epidemiological studies is that they mimic real life circumstances, as opposed to the often artificial environment of a randomized clinical trial.

With respect to hormone replacement research, probably the most artificial aspect of the Women’s Health Initiative trial was that there was no distinction made between women who needed the HRT to relieve their symptoms and those who had no symptoms. If a woman was randomly assigned to the HRT arm of the study she was put on a continuing dose of HRT, whereas if she was randomly assigned to the control arm of the study she was provided with a placebo, which meant that it was highly unlikely that she would take HRT even if symptoms required it. Symptomatic need for HRT was not part of the study design.

To give you an oversimplified parallel to this situation, suppose that a randomized clinical trial was used to ascertain whether or not water was good for a person’s health, and the treatment group was told to drink an extra gallon of water every night before they went to bed. Suppose then that the study found no health benefit from the water and concluded that water was not important to one’s health. That example of course is extreme and somewhat ridiculous, but I believe that it makes a point. And that point can be imagined by the realization that if the water treatment was limited to people who were thirsty and dehydrated it would be found that water makes a great deal of difference to a person’s health.


Specific overall study results from the Women’s Health Initiative (WHI)

Here is a very good review article from the Mayo Clinic about the WHI findings, and here is a scientific presentation on the same study. The treatment group was divided into women who took a combination of estrogen and progestin (Prempro) and women who took estrogen only (Premarin). The results for the group that took combination therapy (estrogen plus progestin) were worse than for the group that took estrogen alone, so I’ll summarize the results for the group that took estrogen alone.

In the estrogen only group, compared with the placebo group, the downside was a slight increased risk of stroke and a slight increased risk of abnormal mammogram (but without an increased risk of breast cancer). The advantages for the estrogen only group (over the placebo group), other than the relief of symptoms, were a decrease in the risk of osteoporosis related hip fractures and a decrease in the incidence of colorectal cancer. There was no difference between the estrogen only group and the placebo group with regard to breast cancer, heart disease, or overall death.


Some important caveats about the overall findings of the WHI study

The average age of women in the WHI study was 63 years, whereas women typically begin HRT much earlier than that. Furthermore, as I alluded to above, the presence or absence of symptoms had no influence on whether or not women were assigned HRT.

When women in the age group 50-59 were analyzed, those who took estrogen only were found to have less heart attacks and coronary artery disease related deaths than those who took the placebo instead. This very important advantage of HRT (estrogen only) may be considered as an added advantage to the other benefits noted above, and would seem to shift the overall balance significantly in favor of HRT for that age group.

We don’t know why the 50-59 age group experienced a reduced risk for coronary artery disease and related death when they took estrogen, as compared to the placebo controls. But I think that it would be logical to assume that the reason may be related to the fact that many women in that group had post-menopausal symptoms that were relieved by estrogen – which has always been the primary reason for post-menopausal women take HRT in the first place.


Recommendations

Given the above facts, it is not surprising that the Mayo Clinic article goes on to recommend HRT (estrogen only) for women who have post-menopausal symptoms that are relieved by HRT and for women who have or are at high risk for osteoporosis. Thus, there are two major advantages to taking HRT: to relieve symptoms which often seriously interfere with one’s quality of life, and to reduce the risk of bone fracture, which is often a terminal event in older women (By causing people to become immobile, hip fractures associated with osteoporosis often lead to a large number of serious health conditions, which often lead to a downward spiral.)

And the article goes on to couch its recommendations in cautious language, involving advice that women talk to their doctor about what to do about this, and listing several other ways to reduce the likelihood of bone disease and heart disease. Also, it notes that women with breast cancer or a history of blood clots should avoid HRT.

Lastly, I have to say that there is one short paragraph in the Mayo Clinic article that I feel is overly cautious, to the extent that it is not even consistent with the rest of the article or with the known facts about HRT, and therefore it is also unnecessarily confusing. That is the part that reads, “One of the previously believed benefits of HRT was that it promoted long term health of post-menopausal women, from reducing the risks of heart disease to making bones stronger. But since that’s no longer the case, here are some alternatives…” As I hope was made clear by the above discussion, we don’t know that “that is no longer the case”. HRT does promote stronger bones, according to all studies that have looked at that issue. And it does apparently reduce the risks of heart disease in relatively younger women, and possibly in all women who take it for symptomatic relief. And finally, there is no question that, by virtue of the symptomatic relief that it provides, it improves quality of life for millions of women.

[GrumpyGreg]

1. I took it for years and ended up with cancer that,luckily for me,

I caught on time.

I have told my daughters to avoid it and "tough it out" the way my mother and grandmother did.

[saged52]

2. completely agree

My mother was on HRT for 17 years and found she had breast cancer last year; it was not necessarily heredity. I am 54 years old and I 'tough it out' as you say; as do all my other same-aged friends. There is no freakin' way we would go any other route! Good advice, Grumpy Greg!

[a kennedy]

5. Nooooooooo, I can't tough it out any more........

:cry: :cry: :cry: I know I should though......have a friend that got breast cancer from HRT too, and she'll kill me if I go on it. Actually I was on it for 5 years, but my doctor took me off for a "rest" because I have since retired. I was on HRT when working because I just could not face the public (I was a receptionist), when having hot flashes 15 - 20 times a day. I can handle them now, well, I can't, but I'm going to just because I'm retired and don't face anyone at that job anymore, but it's still the hardest thing, outside of quitting smoking that I've ever had to live through. :cry:

[azurnoir]

9. Alot depends on family history

If there is a history of breast cancer on your moms side of the family sisters aunts grandmother then you are more at risk, if not then possibly estrogen only is the to go, an RN I work with who has both the family history and went through early menopause before 40 told me she takes Evista which has been shown to have less risk.

[zanne]

14. There's the question of post-menopausal depression...

I'm in the peri-menopausal stage right now and the only symptom I'm having is irritability, but I have a history of depression and I'm worried about that. When I've had it, it was severe depression; the kind that incapacitates. But none of the doctors I've seen about it will even recognize that depression can occur post-menopause. I'm trying to prepare ahead of time because I have heart disease and cannot take HRT. I don't fear the physical symptoms of menopause; to me, they're only physical, after all. Has anybody out there experienced depression with menopause and if so, how did you deal with it?

[Time for change]

18. Here is a pretty good article on postmenopausal depression

http://www.postgradmed.com/issues/2000/09_00/dell.htm

And here is the summary:

For most women, the perimenopause is not associated with depression. In those who do become depressed, mood symptoms tend to decrease at the end of menopause, regardless of previous history of depression. Many of the changes in brain function that affect mood are secondary to changing estrogen levels in the brain. Treatment with estrogen alone may improve mood in women with mild depressive symptoms, but those unresponsive to estrogen and women who have moderate to severe depression need antidepressant therapy.

Nevertheless, this was written in 2000, before the controversy with the possible heart disease connection - so this would be more controversial now.

[Time for change]

3. I'm sorry to hear that - what kind of cancer did you get

According to the latest research, as I note in my OP, and as is described in the articles that I link to, estrogen only HRT is associated with an increased risk of endometrial cancer but a lowered risk of colorectal cancer, and no elevated risk of other kinds of cancer. And it also may have health benefits other than relief of symptoms, especially for women in their 50s or for women who have postmenopausal symptoms.

[GrumpyGreg]

23. Endometrial adenocarcinoma! I had a full hysterectomy

and was cleared.

The first thing my doctor said to me was "Thank God you called when you did!"

[SPKrazy]

25. My Mother Had A Hysterectomy

She was not on HRT because she had a pulmonary embolism in her 30's while on birth control and she was considered to be at risk for that from hormone supplementation (on edit)

a year later she was diagnosed with primary peritoneal adenocarcinoma- basically ovarian cancer cells growing on her peritoneum, all over

the hysterectomy had found "abnormal cells" but no cancer

of course they (doctors) said there was "no connection"

but my guess is that there was fluid and abnormal cells that splashed into her peritoneal cavity and over the next year made the transition to cancer cells

She fought it for 5.5 years and died last October

[DawgHouse]

29. Same thing with my mom

no family history but she did get breast cancer after years of HRT. She tells me all the time that she wishes she'd never taken HRT and she advises me not to.

Glad you are doing well.

[Bjornsdotter]

4. Your name

certainly fits the subject matter.

I will never take any estrogen replacement, I can live with hot flashes, insomnia, and night sweats. I can't live with the problems estrogen replacement can cause.

In college I worked in a pharmacy, every woman complained about the meds, too many problems.

Ironically, I don't personally know one woman in my age group using replacement meds....some have used natural alternatives, but none of us want to go down that other path.

Cheers

[a kennedy]

6. What's your age group???

:grouphug:

[Bjornsdotter]

24. I'm 45

but my friends range from 59 to 38.

Cheers

[OnionPatch]

7. I took them for almost a year

the combo type. :scared: But after the studies came out, I stopped. It was hard. I was having hot flashes about every half hour and waking up in puddles of sweat several times a night. But after trying all sorts of natural things, I found soy. I started taking soy (I use Estroven) every day with vitamin E and magnesium. I was skeptical at first. I didn't think anything "natural" could put a dent in my hot flashes, but amazingly, it has been working very well for me for almost a year now. I have a few hot "spells" a day. I can't even call them "flashes" anymore because they're very mild. I sleep through the nights, now too with only occasion problems. The one thing about taking the soy, is that you have to take it every single day. I had lapses where I would forget and there would be a delayed reaction of about a week where the flashes would return with a fury. Oh and soy is supposed to be great for helping stave off osteoporosis.

Anyway, thanks for the link and post. This is an important topic for all women.

[azurnoir]

8. To be honest

I've never been sure just what the purpose of progesterone was for post menopausal women, progesterone affects the uterus, my mother in law took it for many years and had problems such as heavy bleeding ect, she realized she 65 years old and still having periods, her doctor changed her over to estrogen only and she has not had any problem since.

[Time for change]

12. The purpose of progesterone

Originally, progesterone was often used in combination with estrogen because it was believed that it counteracted the risk that estrogen posed with regard to endometrial cancer.

However, now we see from the study noted above, that the overall health status is probably better with estrogen alone than with estrogen combined with progesterone.

Note that estrogen alone HRT is associated with a lowered risk of hip fracture and colorectal cancer, compared with women who use no HRT at all, in addition to controlling postmenopausal symptoms. And for women in their 50s it is also associated with a protective effect against coronary artery disease.

[REP]

10. Anecdotally, HRT = Death in My Experience

I've never known a woman on HRT who didn't die of breast, uterine or ovarian cancer. My grandmother and mother refused HRT, and when the blessed event of menopause finally arrives, I'll run a mile in tight shoes to avoid HRT. I've had years of night sweats and hot flashes from a chronic condition; if they come back, I know how to cope. I've had cancer, too ... night sweats and day sweats are a hell of a lot easier to deal with.

Incidentally, I worked on a medical journal in the '80s. The risks of HRT were beginning to be recognized then, too.

[Mojorabbit]

11. I went off them for a good while when the study came out

but was miserable. I then went to a nurse specialist in the field for an evaluation on advise from my doc and now have it made up for me in a compounding pharmacy. Low dose Estrogen, progesterone, and a small amt of testosterone cream. I feel like a new woman. It really affected my mood for the better. I had not realized how bad I had been feeling till I went back on the hormones.

[KoKo]

26. What bothered me about latest study was it was based on Premarin/Prempro

instead of the new synthethic estrogens and progesterins in the "patch form." Premarin and Prempro or made from pregnant mare urine which might have very different effect from patch and pills made synthetically.

I've not seen any studies on the effects of the synthetics because they are pretty new. But, if someone is suffering they might be an alternative because they come in very low doses.

[RebelOne]

13. All I can say is that I am fortunate that I never

had any hot flashes or discomforts of menopause. My periods just started tapering off and it was all over.

[sendero]

15. Once again...

... we get a study based on "conjugated equine estrogens" rather than actual estrogen. This is why I feel like the term "medical science" is so often an oxymoron. To believe this study has any relevance to reality at all, you have to accept the fact that horse estrogen, NOT THE SAME MOLECULE as human estrogen, has the same effects in the body as real human estrogen.

The only reason they keep putzing around around horse estrogen is that big pharma can make money on patented estrogen analogues, they cannot on human estrogen.

Anyone wishing to consider HRT should start with the premise that they are going to use REAL HORMONES, not junk. You will have to get them at a compounding pharmacy. HRT using these other things is not HRT, it is taking drugs that are kind of like the hormones your body used to make.

[Time for change]

17. Nevertheless, it works to relieve the symptoms of millions of women

Honestly I do not remember the stated reason why human estrogen is not used.

Do you have evidence that the reason is to help make money for the drug companies, or is that your guess?

[sendero]

22. You give me ...

.. one possible alternative reason. I doubt very seriously if there IS a "stated reason". Better to not state a reason when the reason best be unstated. Why would you use an artificial manufactured drug when the real thing is available?

Doctors are lobbied continually by the drug companies to use their products. This is only one of many cases where drugs are used that are expensive, of marginal effectiveness or even counterproductive.

This is my assertion (I didn't originate it, my wife read it in a book on the subject), and I have no dog in this hunt. Folks should do what they want. My wife takes real hormones and they work very well, although it did take a lot of trial and error to find the perfect balance of estrogen and progesterone. And when she or I gets a prescription from a doctor, I do the research and then I decide whether or not I want to fill/take it. Sometimes, I don't. Ultimately, we are all responsible for our health decisions, and folks who think that doctors cannot be wrong are naive.

on edit: Upon thinking about it, I have a speculation as to why artificial drugs are "justified". Real hormones cannot pass through the digestive tract, so they cannot be taken in oral form. You have to apply a cream, generally daily. Some women might find this to be too inconvenient, but in the name of one's health I'd have to disagree.

[GreenPartyVoter]

16. My mom went off them and took a low dose of Prozac to

help her ditziness but we did kind of wonder if the HRT contributed at all to whatever condition her heart was in that caused her to die (along with years of overeating and underexercising prior to the last two years of her life when she was thin and fit).

[cally]

19. thanks for an informative post

The research on hrt is still not definitive for most of us. I appreciate the new insights you provided.

[Time for change]

20. Thank you - I agree it's not definitive

There is a lot more we should know about it, and there is a lot of data analysis continuing.

[Time for change]

21. Anecdotal evidence of a link between HRT and cancer

There have been a lot of posters to this thread providing anecdotal evidence of a link between HRT and cancer. Consequently I feel the need for some balance on this issue:

There were 192,000 new cases of breast cancer alone in the United States in 2001. Obviously, many of those cases have occurred in women taking HRT, since HRT has been commonly used. On the other hand, the good majority of those cases occurred in women (and some men) who were not taking HRT.

The bottom line is that anecdotal evidence should be considered as being overshadowed when better evidence is available - as it is in this case. At this time, with numerous studies having looked at this issue, the general weight of the evidence is that there is not an association between HRT and overall cancer rate. The most thorough study performed to date is the Women's Health Initiative study that I referred to in the OP, which showed no evidence of an association of HRT with cancer. In fact, there was a negative association with colorectal cancer. We do know that HRT can cause endometrial cancer, but overall cancer incidence does not appear to be changed by HRT.

[Vinca]

27. I'm immediately suspect of any drug that has to be taken daily

for the rest of your life because it "might" do something. When I hit menopause (pre loss of insurance), the doctor wanted to put me on HRT, but I declined. That was before the 2002 findings. I was lucky and got through it fine. Now I have the same suspicions about statin drugs and wouldn't take them even if I could afford them.

[Time for change]

28. I take daily aspirin in order to prevent a heart attack

And will probably do so for the rest of my life. Heart attacks run in my family.

Who knows, I might have had one by now otherwise.