HRT (hormone replacement)
Steve Harris
>
> A friend of mine had this take on the HRT story from yesterday. Any
>comments?
>
>> This is another one of those things where, even with the investigators'
>> public caveats, people can't really make reasonable use of the results.
>> While the numbers are statistically significant, look at what it says in
>> absolute numbers. Heart disease and breast cancer, two of the foci of
>> the study, showed a difference in 7 and 8 cases per 10,000
>> patient-years, which was an increase from 30 to 37 and from 30 to 38 per
>> 10,000. Sure, that a "23 percent increase", but it's more realistically
>> an increase of from 0.3 percent to 0.37 percent risk per patient-year.
>> So, unless I read it wrong, the risk only goes up 0.07 percent on
>> account of the therapy.
COMMENT:
They stopped the PremPro arm of the WIH study before they could tell if the
total mortality was going to increase or not, but it's a safe bet that it
will, since breast cancer is deadlier than hip fractures. As a drug, PremPro
is dead, and I imagine the biggest class action lawsuit in the history of
medicine is brewing against Wyeth, which has been selling Premarin for 60
years.
To quote from the JAMA:
"The absolute excess risk (or risk reduction) attributable to estrogen plus
progestin was low. Over 1 year, 10 000 women taking estrogen plus progestin
compared with placebo might experience 7 more CHD events, 8 more strokes, 8
more PEs, 8 more invasive breast cancers, 6 fewer colorectal cancers, and 5
fewer hip fractures. Combining all the monitored outcomes, women taking
estrogen plus progestin might expect 19 more events per year per 10 000
women than women taking placebo. Over a longer period, more typical of the
duration of treatment that would be needed to prevent chronic disease, the
absolute
numbers of excess outcomes would increase proportionately."
Here's some Q and A from the LA-GRG reading group; Comments by me.
Q:Do you know whether the hormones they were administering in that HRT study
were of equine origin (or otherwise not molecularly identical to
human estrogen and progesterone)? I've been wondering for a while if that
might be behind the increased incidence of cancer with HRT.
COMMENT:
The recent Women's Health Initiative (WHI) trial reported in JAMA and in the
news yesterday, and stopped because of increased breast cancer incidence,
used equine estrogens (Premarin = pregnant mare's urine) plus a progestin
(=synthetic molecule with progesterone-like action, in this case
medroxyprogesterone = Provera). The product actually used is made by Wyeth
and is called PremPro (for Premarin/Provera). Wyeth's stock took a beating,
needless to say.
Q:
My layman's understanding, from what I've read, is that most "estrogen" on
the market today is of equine origin; that human and equine estrogen
are each composed of several different kinds of estrogens, in different
proportions, and that there are substantial chemical differences between
what humans produce and what horses produce.
COMMENT:
Though the most common estrogen product on the market is Wyeth's Premarin
and Prempro, there are many products which contain simple synthetic
estradiol,
same as in the human body. Alas, few trials have used these because drug
companies will not put up research dollars for the trials, because the
native hormone is unpatentable. This is exactly the problem we have getting
research done on vitamins. We don't KNOW what the long term effects of the
pure
estradiol, much less estriol are, in humans. We've just gotten around to
looking at Premarin, and that's been available since WW II, and is the
number #3 selling drug in the country! So don't hold your breath.
Q.
And isn't Progestin also of equine origin?
COMMENT:
No, but progestins by definition (including Provera) are synthetic molecules
not to be found in nature.
Q:
The progesterone I take is Prometrium: of vegetable origin, and supposedly
made to have identical molecules to human progesterone.
COMMENT
That's correct. Only very recently approved as an ethical pharmaceutical,
because of unpatentability issues (no money to get it though FDA trials).
And for the same reason there are few studies on it, and nobody knows really
if
it's going to be better than the progestins. I will guess so, but can't
prove it.
Q: I do not know if there is an identical-to-human estrogen product out
there -- does anyone else on the list know?
COMMENT
There is: Estrace and others. The estradiol patches and vaginal rings also
all release normal human estrogen (human estrogens are estrone, estradiol,
and
estriol-- the first two are available pharmaceutically, and the third from
compounding pharmacists).
Incidentally, the question of "what now?" is about to hit the fan. Either
progesterone or a progestin must be used if an estrogen is taken by women
with a uterus, because of risk of uterine cancer with estrogen alone. But
it's
beginning to look like Provera at least contributes to breast cancer risk
(since the estrogen-only arm of the WHI has not yet been stopped, and some
earlier studies like PEPI have suggested that estrogen alone has a lower
breast cancer induction risk).
We DON'T know if natural progesterone will cause the same breast cancer risk
when given with an estrogen. We don't know if natural estadiol will do so,
when given with a progestin.
Progestins as a class of drugs are starting to look like nasty things, but
we don't know if natural progesterone is better as an estrogen additive. We
are
fairly certain that progesterone alone is safe.
Clearly, the estrogens of all kinds cause the venous and pulmonary clotting
risk
(and probably including increased stroke and heart attack risk, which arises
from coronary and cerebral clotting).
And probably also all non selective estrogens increase breast cancer risk,
though there may be differences, and there are some "SERM" estrogen blocking
drugs
like Evista which work like Tamoxifen and possibly would decrease breast
cancer risk (while still, alas, increasing clotting).
One thing I can guess from the data: any woman with breasts who is bent on
taking an estrogen to prevent colon cancer and osteoporosis, should also be
taking
Evista (raloxifen) and aspirin. And if she has a uterus, also Prometrium
(natural progesterone). Since PremPro has gone down in a big way, it's
probably better to now stay away from both its ingredients, and instead
use estradiol or estratriol for the estrogen, and natural progesterone/
Prometrium. If you can get away with it symptom-wise, Evista/aspirin and
Prometium or Evista/aspirin, is the hormone replacement likely to be the
safest bet. Of course, without the studies we can't know for certain.
Of course, some of this depends on what your prior risk factors for stroke,
breast cancer, heart disease, osteoporosis, and colon cancer are.
SBH
--
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Wayne Alan Simon
All the studies done to date, do not completely agree with one another.
M. Bakker
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> schreef in bericht
news:agiub8$dam$1...@nntp9.atl.mindspring.net...
> will, since breast cancer is deadlier than hip fractures.
In the elderly, 50% dies within a year after a hip fracture.
MB
Rich Andrews
news:agjbh8$ji6$1...@reader1.tiscali.nl:
But they don't die from the fracture. It is like saying that 100% of
people die after birth.
r
--
"I will not be pushed, filed, stamped, indexed, briefed, de-briefed, or
numbered...My life is my own."
"I am not a number. I am a free man."
No. 6
M. Bakker
"Rich Andrews" <nos...@charter.net> schreef in bericht
news:Xns92481E0C5FC7a...@216.168.3.40...
> people die after birth.
No, not directly. But they die as a result of complications and the general
deterioriation (sp?) of their general condition, brought about by the
fracture.
And do you die from breast cancer itself, or from the tumor spreading to
vital organs?
MB
Richard Cavell
news:agiub8
> They stopped the PremPro arm of the WIH study before they could tell if
the
> total mortality was going to increase or not, but it's a safe bet that it
> will, since breast cancer is deadlier than hip fractures.
I refute this. The hip fracture mortality is approaching 100%. Breast
cancer can be cured. HRT has many positive benefits. To simply say
'breast cancer up 26%' does not ipso facto mean that HRT must never be
used.
> Q:Do you know whether the hormones they were administering in that HRT
study
> were of equine origin (or otherwise not molecularly identical to
> human estrogen and progesterone)?
Yes.
> I've been wondering for a while if that might be behind the increased
incidence of cancer with HRT.
Maybe. I doubt it, personally. One estrogen receptor agonist is as good
as another.
> My layman's understanding, from what I've read, is that most "estrogen"
on
> the market today is of equine origin; that human and equine estrogen
> are each composed of several different kinds of estrogens, in different
> proportions, and that there are substantial chemical differences between
> what humans produce and what horses produce.
Yes.
> research done on vitamins. We don't KNOW what the long term effects of
the
> pure
> estradiol, much less estriol are, in humans.
I doubt that. There are oral contraceptive pills containing ethinyl
oestradiol.
> Progestins as a class of drugs are starting to look like nasty things,
I don't think so. It's the oestrogens that cause all the trouble.
Richard Cavell
> But they don't die from the fracture. It is like saying that 100% of
> people die after birth.
It's legitimate epidemiology.
The C-word (cancer) causes people to panic, whereas it's less dangerous
than a fractured hip.
Rich Andrews
Someone better versed in Geriatric Medicine might be able to help us gain
some insight into the hip fracture -> death statistic. There is no point
in discussing possible causal relationships when the work has already been
done.
rich
Hillary Israeli
Steve Harris <sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
*will, since breast cancer is deadlier than hip fractures. As a drug, PremPro
*is dead, and I imagine the biggest class action lawsuit in the history of
*medicine is brewing against Wyeth, which has been selling Premarin for 60
*years.
Why is Wyeth's fault? The drug was approved by the FDA. The drug was
prescribed by thousands of MDs. The drug was taken by thousands
(millions?) of women. Don't these people bear any responsibility??
--
hillary israeli vmd http://www.hillary.net in...@hillary.net
"uber vaccae in quattuor partes divisum est."
newly minted veterinarian-at-large :)
Tim Fitzmaurice
> "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
> news:agiub8
>
> > They stopped the PremPro arm of the WIH study before they could tell if
> the
> > total mortality was going to increase or not, but it's a safe bet that it
> > will, since breast cancer is deadlier than hip fractures.
>
> I refute this. The hip fracture mortality is approaching 100%. Breast
> cancer can be cured. HRT has many positive benefits. To simply say
> 'breast cancer up 26%' does not ipso facto mean that HRT must never be
> used.
And this is the risk benefit analysis most people stop halfway
through....are the benefits of the drug overall still worth it in
the face of these new levels of side effects is the right question...not
to mention that they did notice other downgraded effects....at least
according to the figures the BBC quoted last night...ie the reduced colon
(IIRC) cancer of a similar level to the increase in breast cancer. New
side effects are worrying and need to be analysed, but they arent
automatically going to block the drug as being of use.
Failure to address the analysis would be the negligence that should
trigger a lawsuit, not simply finding some in such a large trial. I really
want to see the paper itself as there was no mention of development f
dementia on the news last night and thats one big area of interest when
talking oestrogen.
Tim
When playing rugby, its not the winning that counts, but the taking apart
ICQ: 5178568
Michael Roose
wrote:
|
|Someone better versed in Geriatric Medicine might be able to help us gain
|some insight into the hip fracture -> death statistic. There is no point
|in discussing possible causal relationships when the work has already been
|done.
Mother-in-law recently passed in nine months after a reduction of her
femoral head. I was told by a number of orthos that her stats were
50% for 12 months. When asked why, they said "Systemic issues; we
really don'y know; the causes are many."
Steve Harris
>In <agiub8$dam$1...@nntp9.atl.mindspring.net>,
>Steve Harris <sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>
>*will, since breast cancer is deadlier than hip fractures. As a drug,
PremPro
>*is dead, and I imagine the biggest class action lawsuit in the history of
>*medicine is brewing against Wyeth, which has been selling Premarin for 60
>*years.
>
>Why is Wyeth's fault? The drug was approved by the FDA.
So was fenfluramine. Class action settlement has been 5.8 billion. So was
silicone for breast implants, and that broke Dow (however unfairly).
>The drug was
>prescribed by thousands of MDs. The drug was taken by thousands
>(millions?) of women. Don't these people bear any responsibility??
Sure. It all depends on what information is locked up on Wyeth's files. I
personally don't think that Wyeth really knew or even had reason to suspect
the stuff would prove to increase breast cancer-- at least up to a few years
ago, or it wouldn't have funded part of this WHI study. So they may escape.
I myself have suspected that estrogen/progestin combos were going to take a
rap since the outcome of the HERS trial recently. But that also was a
surprise, and the data we've had before that didn't really suggest it.
Steve Harris
>> I've been wondering for a while if that might be behind the increased
>incidence of cancer with HRT.
>
>Maybe. I doubt it, personally. One estrogen receptor agonist is as good
>as another.
Except there's no such thing as a simple estrogen receptor agonist. There
are a number of different estrogen receptors, and each estrogen has a
different spectrum of affinity for them.
>> research done on vitamins. We don't KNOW what the long term effects of
>the
>> pure
>> estradiol, much less estriol are, in humans.
>
>I doubt that. There are oral contraceptive pills containing ethinyl
>oestradiol.
Which is not the same thing as estradiol. Moreover, I'm not aware of any
long term studies of the health effects of birth control pills vs placebo,
in a prospective randomized study in women of an age to get breast cancer
(ie in post menopausal women). Ethynl estradiol is specifically used in
women under 35 who are generally too young to get breast cancer (ie, their
baseline incidence is very low), so any effect it might have in that
direction would have gone undetected. The same is true for heart disease. It
IS known that birth control pills vastly increase clotting risks in veins in
young women.
>> Progestins as a class of drugs are starting to look like nasty things,
>
>I don't think so. It's the oestrogens that cause all the trouble.
I gave my reasoning. The estrogen-alone arm of the WHI is still going, and
it wouldn't be if the breast cancer risk increase were the same.
PEPI trial results are also consistant with a bad effect of progestins when
combined with estrogens, on the post menopausal breast.
Rich Andrews
news:6noriu4toomajtt2p...@4ax.com:
That figure sounds about right. My mother died of a massive stroke after
having surgery to pin a fractured hip. She was in Phys. Therapy when it
hit. It had been about 1 week after the operation.
r
john
"Hillary Israeli" <hil...@hillary.net> wrote in message
news:slrnaiqt94....@manx.misty.com...
>
> Why is Wyeth's fault? The drug was approved by the FDA. The drug was
> prescribed by thousands of MDs. The drug was taken by thousands
> (millions?) of women. Don't these people bear any responsibility??
>
Yeah, for being brainwashed by the medical profession.
john
Hillary Israeli
john <vacc...@nospam.com> wrote:
*
*"Hillary Israeli" <hil...@hillary.net> wrote in message
*news:slrnaiqt94....@manx.misty.com...
*
*>
*> Why is Wyeth's fault? The drug was approved by the FDA. The drug was
*> prescribed by thousands of MDs. The drug was taken by thousands
*> (millions?) of women. Don't these people bear any responsibility??
*
*Yeah, for being brainwashed by the medical profession.
Interesting opinion. Anyone who takes a prescribed medication, or for that
matter prescribes a medication, has been brainwashed by the medical
profession? I do both quite frequently and consider my brain quite
unwashed, thanks. :)
jril...@bigpond.net.au
Israeli) wrote:
>In <agkjpv$7qg$1...@paris.btinternet.com>,
>john <vacc...@nospam.com> wrote:
>
>*
>*"Hillary Israeli" <hil...@hillary.net> wrote in message
>*news:slrnaiqt94....@manx.misty.com...
>*
>*>
>*> Why is Wyeth's fault? The drug was approved by the FDA. The drug was
>*> prescribed by thousands of MDs. The drug was taken by thousands
>*> (millions?) of women. Don't these people bear any responsibility??
>*
>*Yeah, for being brainwashed by the medical profession.
>
>Interesting opinion. Anyone who takes a prescribed medication, or for that
>matter prescribes a medication, has been brainwashed by the medical
>profession? I do both quite frequently and consider my brain quite
>unwashed, thanks. :)
So you have a dirty mind? Join the club :)
jl