|
The
need to oppose estrogen with a progestagen
>Hi,
I am new to this newsgroup. I am having problems when I take the
Provera during the last weeks of my cycle.I feel quite good when I take
the Premarin but as soon as I start on the Provera, I get hot flashes,
feel dizzy and just plain rotten.
>>Miserable
isn't it!!! My doctor finally took me off the provera altogether...she
said the provera was just so you would have your period at the same time
every month.. for those kinds of side effects, who cares? Anyway, have
been taking the premarin .9 now by it's self for about 8 months and I feel
like a new person.. so hang in there.. it's got to get better.
If you still have your
uterus intact and take .9 mg. of Premarin you are putting yourself at very
great risk of getting endometrial hyperplasia at best and uterine cancer
at worst.
Just
how great a risk? Try10 % **per year** according to one study, [more below]
It is not given just
to regulate the period - your doctor lied to you. It is true that
Provera will regulate your period if it is irregular. Estrogen causes
the lining of the uterus (endometrium) to build up. When you take
provera or cycrin for a few days and then stop it your body is signaled
to have a period. This chemically induced cycling can go on long
after your body would no longer normally have periods. It is also
being prescribed experimentally as a constant dose of estrogen/provera
which doesn't result in periods, but the suppressive effect of the provera
causes the endometrium to not build up. If your doctor agrees to
let you take Premarin .9 mg. without Provera or another progestin, you
should have your endometrium monitored closely with at least an annual
endometrial biopsy along with the pap smear. There is more than one
kind of progestin. Did you
try micronized progesterone? I am appalled that your doctor would
treat you in this fashion without telling you how dangerous it is.
fiona
Very
clearly put Fiona. The WHI is doing a 15 year study on HRT and they <were>
going to have a group of women with a uterus on unopposed estrogen
but when they found out from the PEPI trial that that unopposed estrogen
group had 10 % hyperplasia in the first year they cancelled that part of
the study and moved those women into the estrogen/progesterone group.
I found
this information in the Journal club discussion session with Dr.
Barrett-Connor, ( Estrogen Replacement Therapy and Heart Disease:A Discussion
of the PEPI Trial), online at
http://www.ama-assn.org/special/womh/library/scan/vol_1/no_1/jcr.htm
The
PEPI trial used .625 mg premarin, I assume .9 mg premarin would have an
even greater effect on the endometrium. [ see next point ]
Last
December we discussed the so called low
dose estrogen study extensively on the ng. The full text of this study
can be found online http://www.ama-assn.org/sci-pubs/journals/most/recent/issues/inte/70361..htm
This
24 month study used unopposed Estratab and not Premarin and found that
the higher the dose the greater the number of women who developed hyerplasia.
From Table 2 in the study, out of 102 women taking .625 mg/d,
16 women developed hyperplasia before the 24 months were up and withdrew
from the study. I could not read the table for the 1.25 mg/d on my screen,
but using a little bit of arithmetic I determined that out of 100 women
taking the higher 1.25 mg/d, ***33*** developed hyperplasia. That is 33%.
If
hyperplasia is not a worry, than maybe the mortality figures in the Upsala
Sweden study of 23,346 women taking hormones will help.
Schairer
C, Adami HO, Hoover R, Persson I Cause-specific mortality in women receiving
hormone replacement therapy. Epidemiology 1997 Jan;8(1):59-65
This
is the abstract posted to the ng by Steve Harris under the heading <HRT
(combination therapy) and uterine cancer risk> on Sept. 17, 1997. It is
in the deja news archives, or look for it on medline.
From the abstract:
"Mortality
from endometrial cancer was not related to the prescription of weak estrogens
or an estrogen-progestin combination, but mortality was 40% higher in women
prescribed more potent estrogens without a progestin."
While
you are looking at medline, (I used PubMed at http://www4.ncbi.nlm.nih.gov/PubMed
) read the abstract for the reference I found at the end of the low dose
estrogen study. This one found 20% hyperplasia in one year using .625 mg
premarin alone.
Woodruff
JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women
taking conjugated estrogens (Premarin) with medroxyprogesterone acetate
or conjugated estrogens alone. Am J Obstet Gynecol. 1994;170(5 pt 1):1213-1223.
And
again if it is endometrial cancer rather than hyperplasia that concerns
you, look for the abstract of the meta analysis listed below. The relative
risk of getting endometrial <cancer> if you take unopposed estrogen
for 10 years is 9 and a half times that of women who do not take hormones.
Not many women die of endometrial cancer but they give mortality figures
too.
Grady
D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement
therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol. 1995;85:304-313.
I
wonder how many doctors will prescribe estrogen alone (with biopsies every
six months to a year) now that they have the alternative of prescribing
Raloxifene?
And of course as Fiona stated, there are other progestogens to use other
than Provera, just not as well tested.
Kathryn
I too thought the PEPI trial
found 33% with uterine dysplasias after its short term unopposed estrogen
use. And it was much higher in the recent "low estrogen" trials when the
doses got beyond 0.3 estrogen. And 50% of the women dropped out of that
trial and when it got up to the 1.25 doses I believe is where they realized
how dangerous this stuff was to be used unopposed.
And two years is way
too short to know which of the dysplasias will convert to cancer. It took
about 7-10 years to find this out after the 1960's hype of unopposed estrogens.
I wonder why this bad unopposed stuff is trying to make a comeback?
They must realize now that trying to stuff the combination down as Prempro
was a disaster and now are back to just trying to using it unopposed again
and monitoring it more closely. But why? Why not just lay off all the hype
that it does anything productive anyway for the non-surgical woman.
Oh right, I just got
it. There used to be 60% of the women castrated who could take it unopposed
and that has now dropped to 30% and hopefully will be dropping even more
as women no longer race to get "their" hysterectomies. So the unopposed
estrogen market has sharply dropped, is getting competition from "designer"
estrogen substitutes and they must be trying like crazy to get a new generation
of non-surgical women hooked on their drugs.
And to keep in mind
that all they used in the "low estrogen" studies was the ultrasound
to check the endometrium, and not endometrial biopsies. There are no long
term studies at all to validate the uterine ultrasound findings. They just
propose that if the endometrium does not grow more than "x" millimeters
when using unopposed estrogens, that it is "okay" but they don't know if
this is really true because ......yawn....there are no long term studies.
(Where have I heard this before?)
I would love to see
this MDs written informed consent form when he prescribes 0.9 mg unopposed
estrogen.
shelly
I have found a series of
letters to the Editor on the JAMA site http://www.ama-assn.org/public/journals/jama/jamahome.htm
which are relevant to our recent postings about unopposed estrogen use.
I am posting 2 items of information which backup statements made by Sherbaker
and Shelly - Sherbaker's claim that unopposed estrogen continues to be
prescribed, and Shelly's regular claim that studies being quoted are based
on estrogen-only investigations. A third paragraph points out the (admittedly
low) risk of resultant hysterectomy even with regular endometrial biopsies.
Clinical trials are designed
and performed with Food and Drug Administration (FDA) guidance and according
to FDA requirements. To document the protective effect of an estrogen-progestin
combination against endometrial hyperplasia, the FDA has required both
a placebo group and an unopposed estrogen group in clinical trials.
During the design phase
of PEPI, the investigators concluded that assigning women with a uterus
to an unopposed estrogen arm was scientifically important and ethically
appropriate because
-
information on the association
between estrogen and cardiovascular disease had been obtained almost exclusively
from studies of unopposed estrogen;
-
excluding women with a uterus
from 1 treatment group would limit the inferences that could be drawn from
PEPI; and (
-
the American College of Obstetricians
and Gynecologists includes unopposed estrogen as a treatment option in
women with a uterus, provided an annual endometrial biopsy is obtained.
Additionally, and despite the
well-known association between unopposed estrogen therapy and endometrial
hyperplasia and carcinoma, many women still prefer and many physicians
still prescribe this regimen.
JAMA Letters - June 26,
1996
To the Editor.--The PEPI
trial group recently demonstrated that in 94% (34/36) of postmenopausal
women who developed endometrial hyperplasia in association with estrogen-only
replacement, progestin therapy was effective in reversing the hyperplastic
changes, while the remaining patients were refractory to progestin therapy.
The next natural question that should be considered is whether there are
any factors that can reliably predict response to progestin therapy in
patients with endometrial hyperplasia. The importance of predicting response
to progestin therapy is obvious, considering that the alternative for many
patients is hysterectomy |