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Time for change Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:31 PM
Original message
The Controversy Over Post-Menopausal Estrogen Use
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 Womens 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 Womens 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 persons 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 ones 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 persons health.


Specific overall study results from the Womens 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 Ill 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 dont 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 ones 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 thats no longer the case, here are some alternatives As I hope was made clear by the above discussion, we dont 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.
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Warpy Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:37 PM
Response to Original message
1. And after all this horse shit, they still don't have a clue
in the world what causes hot flashes! They have never studied the mechanism, haven't a clue what sort of endocrine cascade happens and what triggers it, why some women have a miserable time and others never experience them, none of it.

If men got hot flashes, they'd not only know what causes them, they'd be cured in infancy.
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Gormy Cuss Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:43 PM
Response to Reply #1
3. Written like a woman with experience.
I tend to think that HRT should only be used by women who are completely miserable without it.
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sgxnk Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:50 PM
Response to Reply #3
7. both men and women
are hurt by the conventional medical establishment's stance towards hormones.

men also, who would be greatly benefited by supplemental testosterone use, are severely hampered by extremely restrictive stance in general towards exogenous T administrations.

there are progressive clinics that do provide testosterone based HRT for men in decent quantities, but they are outliers in the medical community because much as marijuana etc. have been demonized, so have AAS (anabolic androgenic steroids) by myths promoted by the media.

women can elect plastic surgery for appearance enhancement that is orders of magnitude more dangerous than HRT is for men, but men are prohibited by law from getting a script for HRT for appearance/aesthetics. that is blatantly sexist

also, on the congressional hearings to schedule AAS, *both* the AMA and the DEA testified AGAINST making steroids (HRT for example) controlled substances. they were shot down based on the "do it for the children" scare mongering and the strength of the fear of the evil athletes.

humans, evolved to live for FAR less time that we now live (into our 70's) and one of the primary reasons we suffer aging, etc. (besides terrible diets, etc.)is due to hormonal issues

quality of life, not to mention aesthetics can be greatly improved for men and women by taking supplemental hormones but the medical establishment, the media etc. have demonized them

both men and women suffer. and it is again absrud that dangerous plastic surgery is legal, but androgen therapy for appearance is not

those who support "choice" TRULY support the notion that it should be up to the individual and/or their doctor. not the govt.

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SharonAnn Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 10:31 PM
Response to Reply #3
11. That would be me. I've been on for several years and am just
miserable without it. Can't get a good night's sleep, wake up hot and sweaty, etc.

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HysteryDiagnosis Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:48 PM
Response to Reply #1
6. Cured in infancy?? Many men never leave it.... ;)
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formernaderite Donating Member (1000+ posts) Send PM | Profile | Ignore Sat Aug-19-06 12:03 AM
Response to Reply #1
16. perhaps there is nothing to cure...as my wise wife would say
perhaps we should let NATURE take it's course...and stop fooling with it.
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Warpy Donating Member (1000+ posts) Send PM | Profile | Ignore Sun Aug-20-06 01:22 AM
Response to Reply #16
20. Neither of you has suffered with frequent ones
I take it.
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HysteryDiagnosis Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:42 PM
Response to Original message
2. Wild Yam.... Dioscorea, and Diosgenin. It doesn't get any
simpler than that.


1: Planta Med. 2004 Mar;70(3):220-6.Click here to read Links
In vivo antiosteoporotic activity of a fraction of Dioscorea spongiosa and its constituent, 22-O-methylprotodioscin.

* Yin J,
* Tezuka Y,
* Kouda K,
* Le Tran Q,
* Miyahara T,
* Chen Y,
* Kadota S.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.

The antiosteoporotic activity of the 90 % EtOH fraction of the water extract of rhizomes of Dioscorea spongiosa and methylprotodioscin, its major constituent, were examined in the model of postmenopausal bone loss using ovariectomized (OVX) rats or mice. After 6 weeks treatment, the proximal tibia of rats or mice and the distal femora of mice were scanned by peripheral quantitative computed tomography (pQCT). Both the 90 % EtOH fraction (100 mg/kg/d) and methylprotodioscin (50 mg/kg/d) significantly inhibited bone loss in bone mineral content (BMC) and bone mineral density (BMD) in total, cancellous and cortical bones, and the decrease in bone strength indexes induced by OVX, without side effect on the uterus.

PMID: 15114498

1: Biol Pharm Bull. 2004 Apr;27(4):583-6.Click here to read Links
Antiosteoporotic activity of the water extract of Dioscorea spongiosa.

* Yin J,
* Tezuka Y,
* Kouda K,
* Tran QL,
* Miyahara T,
* Chen Y,
* Kadota S.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

After 60 MeOH and water extracts of natural crude drugs were screened for their ability to stimulate osteoblast proliferation, four MeOH extracts (Cynomorium songaricum, Drynaria fortunei, Lycium chinense, Rehmannia glutinosa) and seven water extracts (Cornus officinalis, Dendrobium nobile, Dioscorea spongiosa, Drynaria fortunei, Eucommia ulmoides, Lycium chinensis, Viscum coloratum) showed that potent activities were evaluated for inhibition of osteoclast formation. The results indicated that the water extract of D. spongiosa not only showed the strongest stimulation of osteoblast proliferation but also possessed potent inhibitory activity aganist osteoclast formation, whereas it showed lower cytotoxicity in osteoblast and bone marrow cells. A further in vivo experiment determined the antiosteoporotic activity of this extract, in which it inhibited the decrease in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in ovariectomized rats.

PMID: 15056872
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sgxnk Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:44 PM
Response to Reply #2
4. speaking of yams and hormones
yams are also the source that testosterone is synthesized from , to use pharmaceutically iirc
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HysteryDiagnosis Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:46 PM
Response to Reply #4
5. Wild Yam in capsules is not a bad option.... for men and
women alike.

http://www.lef.org/protocols/metabolic_health/osteoporo...
Causes of Osteoporosis: Bone Remodeling

Osteoporosis is defined as a reduction of bone mass, or bone density, which causes the bones to become brittle and fragile. People afflicted with osteoporosis are at increased risk of a range of fractures, including fractures of the hip, spine, and wrist. Fractures associated with osteoporosis are debilitating and costly (Melton LJ 2003; Woolf AD et al 2003). Mortality rates one year after hip and spine fractures have been reported to be as high as 30 percent (Rossell PA et al 2003; Kanis JA et al 2004). Many studies report high rates of institutionalization, loss of function, and death after hip and spine fractures.

Bone is living tissue comprising both organic protein matrix (30 percent) and various minerals (70 percent). Throughout life, cells known as osteoblasts construct bone matrix and fill it with calcium. At the same time, cells called osteoclasts work just as busily to tear down and resorb the bone. This fine balance is regulated by many factors, including systemic hormones and cytokines. Bone mass reaches its peak by the middle of the third decade of life and plateaus for about 10 years. During this time bone turnover is constant, meaning bone formation approximately equals bone resorption.
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sgxnk Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 08:51 PM
Response to Reply #5
8. i agree
so is HRT, which is available through the more progressive clinics. but absurdly expensive due to the congressional demonization of AAS
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azurnoir Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 09:10 PM
Response to Original message
9. At the time f the 2002 study was
Edited on Fri Aug-18-06 09:19 PM by azurnoir
released I questioned the validity of the study, it seemed odd that 2 studies done less than 5 years apart could come to such opposite conclusions. The manner in which the 2002 study was released to the public was meant to be sensationalized, breast cancer rises 26% in women taking HRT. What never got released to the public was the "what this means to the individual" addendum, which explained that in control groups of approximately 3500 women not on HRT 3 developed breast cancer vs. 4 who who developed breast cancer in the group of 3500 women who were on HRT. Meaning according to the study the chances increased by 1 in 3500 a different picture from 26% increase although in fact meaning the same thing. What should also be kept in mind is that this study came from a Bush controlled WHI and NIH, something which should cast doubt on any figures pertaining to womens health.
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woodsprite Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 10:25 PM
Response to Original message
10. And if you have had endo cancer, you try to tough it out cold turkey...
:( I woke up one morning 4 months after surgery and have been walking and moving like a 90 yo since (I'm only 43). The doc said "Oh, surgical menopause symptoms have finally hit." He likened it to a truck going 70 mph and hitting a brick wall. I've even been told try to stay away from phytoestrogens, so I'm on calcium, vitamin D, magnesium, Omega 3, MSM, cinnamon, q10, and a multivitamin - no soy. I've been feeling totally miserable and creaky. I've tried adding a bit of ground flax seed and my joints have been feeling better. Not great, but better (I can stand to cook, I can walk up/down the stairs without leaning heavily with both hands on the rail). Probably working a bit because it contains PHYTOESTROGENS! UGH!!! I'll check it out with the doctor in October, but I'm gonna try it until then.
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Time for change Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 10:49 PM
Response to Original message
12. I accidentally posted this on GDP, so I'm going to repost on GD
Sorry for the inconvenience.

The reason that I'm moving this is that I do not consider this to be a political issue - rather, I was posting it because I think it's an important medical issue. Ironically, out of the more than a hundred OPs that I've posted on DU, this is the very first one where I made no effort to criticize the Bush administration or any other Republican. And this is the one that I accidentally posted on GD-P
:blush:

So please, if you'd like to continue the conversation, go to this site on GD, so that I don't have two identical posts going:
http://www.democraticunderground.com/discuss/duboard.ph...
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a kennedy Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 10:51 PM
Response to Original message
13. So.....can I start taking prempro again????
I'm dying here, don't sleep, crabby, having hot flashes so often that I want to just go nekid all the time......HELP!!! I'm 56 years old.
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Time for change Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 11:16 PM
Response to Reply #13
14. I can't know for sure without knowing more about you - however,
as noted in the OP, most women who have the kind of problems that you describe should probably be taking estrogen replacement to control their symptoms. I suggest that you talk to your doctor about the Mayo Clinic article that I reference in my OP. It might be better, however, to use premarin (estrogen only) rather than a combination estrogen and progestin.

Also, if you don't mind, you might want to re-post your response on GD, where I moved this post to (see my response # 12). One person has responded to the post so far, saying that she took HRT and developed cancer, and I think it would be good for people reading that post to know that some people really need HRT. Here is the link:
http://www.democraticunderground.com/discuss/duboard.ph...
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a kennedy Donating Member (1000+ posts) Send PM | Profile | Ignore Fri Aug-18-06 11:27 PM
Response to Reply #14
15. Thank you
I will. :hug:
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azurnoir Donating Member (1000+ posts) Send PM | Profile | Ignore Sat Aug-19-06 12:07 AM
Response to Reply #14
17. There is also Evista
which has been shown to have a lower incidence of breast cancer.
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HysteryDiagnosis Donating Member (1000+ posts) Send PM | Profile | Ignore Sat Aug-19-06 07:01 AM
Response to Reply #14
18. There are also the cabbage family vegetables which have been
Edited on Sat Aug-19-06 07:07 AM by 4MoronicYears
proven to help fight cancer. One particular extract of cabbabe I believe, perhaps broccoli has the following properties.


1: Sundar SN, Kerekatte V, Equinozio CN, Doan VB, Bjeldanes LF, Firestone GL. Related Articles, Links
Abstract Indole-3-Carbinol (I3C) selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cells.
Mol Endocrinol. 2006 Aug 10;
PMID: 16901971

2: Rahman KW, Li Y, Wang Z, Sarkar SH, Sarkar FH. Related Articles, Links
Abstract Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells.
Cancer Res. 2006 May 1;66(9):4952-60.
PMID: 16651453

3: Qi M, Anderson AE, Chen DZ, Sun S, Auborn KJ. Related Articles, Links
Free in PMC Indole-3-carbinol prevents PTEN loss in cervical cancer in vivo.
Mol Med. 2005 Jan-Dec;11(1-12):59-63.
PMID: 16557333

4: Moiseeva EP, Fox LH, Howells LM, Temple LA, Manson MM. Related Articles, Links
Abstract Indole-3-carbinol-induced death in cancer cells involves EGFR downregulation and is exacerbated in a 3D environment.
Apoptosis. 2006 May;11(5) :799-812.
PMID: 16532375

5: Wang TT, Milner MJ, Milner JA, Kim YS. Related Articles, Links
Abstract Estrogen receptor alpha as a target for indole-3-carbinol.
J Nutr Biochem. 2005 Nov 28;
PMID: 16488130

6: Fan S, Meng Q, Auborn K, Carter T, Rosen EM. Related Articles, Links
Abstract BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells.
Br J Cancer. 2006 Feb 13;94(3):407-26.
PMID: 16434996

7: Brew CT, Aronchik I, Hsu JC, Sheen JH, Dickson RB, Bjeldanes LF, Firestone GL. Related Articles, Links
Abstract Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells.
Int J Cancer. 2006 Feb 15;118(4):857-68.
PMID: 16152627

8: Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS, Crowell JA, Hurwitz A. Related Articles, Links
Abstract A phase I study of indole-3-carbinol in women: tolerability and effects.
Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1953-60.
PMID: 16103443

9: Aggarwal BB, Ichikawa H. Related Articles, Links
Abstract Molecular targets and anticancer potential of indole-3-carbinol and its derivatives.
Cell Cycle. 2005 Sep;4(9):1201-15. Epub 2005 Sep 6. Review.
PMID: 16082211

10: Xue L, Schaldach CM, Janosik T, Bergman J, Bjeldanes LF. Related Articles, Links
Abstract Effects of analogs of indole-3-carbinol cyclic trimerization product in human breast cancer cells.
Chem Biol Interact. 2005 Apr 15;152(2-3):119-29.
PMID: 15840385

11: Rahman KW, Sarkar FH. Related Articles, Links
Abstract Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3'-diindolylmethane-induced apoptosis in breast cancer cells.
Cancer Res. 2005 Jan 1;65(1):364-71.
PMID: 15665315

12: Chang X, Tou JC, Hong C, Kim HA, Riby JE, Firestone GL, Bjeldanes LF. Related Articles, Links
Abstract 3,3'-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice.
Carcinogenesis. 2005 Apr;26(4) :771-8. Epub 2005 Jan 20.
PMID: 15661811

13: Garcia HH, Brar GA, Nguyen DH, Bjeldanes LF, Firestone GL. Related Articles, Links
Abstract Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex.
J Biol Chem. 2005 Mar 11;280(10):8756-64. Epub 2004 Dec 20.
PMID: 15611077

14: Rahman KM, Li Y, Sarkar FH. Related Articles, Links
Abstract Inactivation of akt and NF-kappaB play important roles during indole-3-carbinol-induced apoptosis in breast cancer cells.
Nutr Cancer. 2004;48(1):84-94.
PMID: 15203382

15: Lee IJ, Han F, Baek J, Hisatsune A, Kim KC. Related Articles, Links
Abstract Inhibition of MUC1 expression by indole-3-carbinol.
Int J Cancer. 2004 May 10;109(6):810-6.
PMID: 15027113

16: Chatterji U, Riby JE, Taniguchi T, Bjeldanes EL, Bjeldanes LF, Firestone GL. Related Articles, Links
Abstract Indole-3-carbinol stimulates transcription of the interferon gamma receptor 1 gene and augments interferon responsiveness in human breast cancer cells.
Carcinogenesis. 2004 Jul;25(7):1119-28. Epub 2004 Feb 26.
PMID: 14988219
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Iniquitous Bunny Donating Member (1000+ posts) Send PM | Profile | Ignore Sat Aug-19-06 09:42 AM
Response to Original message
19. I'd personally rather take none or as little as possible.
For some of us, the "large risk of increase in endometrial cancer" taking HRT is not a brush aside kind of matter. My mother has been in remission from stage 2 endometrial cancer for 6 years after treatment and a radical hysterectomy at 50 (she had not yet reached menopause naturally at the time of diagnosis). I'm 34 years old and likely have another 20 years to think about this (although my family history of late menopause adds more risk), but not everyone has the genetics to simply ignore the matter of endometrial cancer. :(

Endometrial cancer is also the most common type of cancer in the female reproductive organs themselves, so concern isn't something to be ignored either.

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