JoanofArdmore

I totally agree O4P!I was just coming to say that.I'm a total emmy, but have always loved and respected Arlen.

And I see the title as meaning "never give in and lie in bed".Because Senator Spector was in the senate all through his tx.He delivered speeches bald as an agg from chemo, and skinny with it.He never gave in, while he was fighting.He is quite old.

How long we live because of  fighting the cancer  isnt the point, I think.How, and THAT we live through tx , is. 

As Obama 4 President says,he did survive a lot(of tx).He is old.And he never stayed home lying in bed, drugged to the nines. I take my hat off to him!

Joan Hussein 

Paulette, no, I've not seen a doc.I refuse docs.I had enough docs in the year of my tx to last a lifetime.

And enough radiation-full tests.

No more for this cripple.

Especially since, for my problems there are 2 options:drugs, surgury.

I chose neither.

I chose Traumeel! 

Edge has said that the "plantar fasciitis" of enormous pain was actually a form of tendonitis.Get this:An estrogen deficiency form of tendonitis of the foot."You can tell because it doesnt respond to the foot-stretching exercises which help plantar fasciitis". 

And the stretches did NADA for me.So--tendonitis.

Grrrrr.

Lynn, good.We might as well be of good cheer, and happy we are OK, and here.

I am older than you, 66.I was 12 years post meno at DX!Not a lot of estrogen for starters.Four years of hormone therapy did me in.You youngsters have a better chance of coming out of this faster.

I will have to wait till my supplimental estrogen sllllooooooowly comes back enough to ease the pain.

My {{{Shirley}}}!!!.Great to see you, Sweetie!

I hate to tell YOU where I've been.But I know you wont hold it against me.

I'm working online for the Obama campaign.Our primary is coming up on April 22.It is a closed primary, and we had to get our Demmy voters registered.AND our Republicans for Obama. 

Now all are registered, but we are still engrossed in poll-watching,persuasion, other issues.

LOL and next comes your primary! 

Much love to you, and I'm so happy you are having uneventful HT!You've got estrogen to spare!You're HOT!!

hugs, j 

When I was on Taxotere, it gave me mucusitis.My mucus membranes from head to toe were inflamed and would bleed.

Taxane, Taxotere, sister drugs.

I would bet this is your problem.

My nose would bleed for no reason.I'd be standing on line at Whole Foods (with my black fingernails from Adriemycin) and feel my nose running.And be afraid to wipe it lest it be bleeding.(And afraid NOT to for same reason!)

And I often had blood in my stools, or on the paper.

My onc insisted I have a colonoscopy when I was through chemo (bc can go to the colon).My gastroenterologist pronounced me fine!Hemmorhoids, he said, but I knew it was the Taxotere thing, even though I was done Tax for a few weeks by then.

It doesnt heal up the moment you stop the drug!

I say do what you want to.The blood will clear up by itself, eventually.

(Has your onc ordered a colonoscopy?)

A sister called FOO posted this link some time ago.I dont think it got the attention it deserved.

Doesnt just the first paragraph remimnd us of....we on AIs?

Yes.

Science News
for Kids

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Published by
Society for Science & the Public

Week of Jan. 5, 2008; Vol. 173, No. 1 , p. 8

A Different Side of Estrogen

Second receptor complicates efforts to understand hormone

Sarah C. Williams

The mice in Jan-Åke Gustafsson's lab are obese, their bones are brittle, and their spleens are unusually big. The female mice produce fewer and smaller litters than normal mice. They also are more likely to develop high blood pressure and a disease that resembles human leukemia. In fact, problems of one sort or another afflict almost every major organ system in their fragile, overweight bodies.

What these mice lack is the gene for an important molecule needed to fully respond to the hormone estrogen. Known as estrogen receptor beta (ERb), this molecule mediates most of the effects of estrogen not traditionally associated with the hormone. By genetically engineering both male and female mice without the receptor, researchers are digging up clues to its many important roles in people.

Discovered only a decade ago, the beta receptor has been found to protect against cancer, keep the immune system in check, help serious trauma patients survive their injuries, and keep people from being too anxious. A recent spate of studies on the receptor could lead to a new generation of hormone-based drugs for infertility, breast cancer, irritable bowel syndrome, depression, and a myriad of other conditions.

"Estrogen receptor beta, in particular, is involved in many, many tissues. It shows that estrogens are extremely important not only in reproduction, which everybody knows, but in other aspects of health as well," says Gustafsson, of the Karolinska Institute in Stockholm, Sweden.

Estrogen, a hormone that circulates in the blood, comes mainly from the ovaries, but is also made in small quantities by the placentas of pregnant women, the liver, adrenal glands, and breasts. In males, certain cells in the testes produce low levels of estrogen.

Estrogen affects various organs by entering cells and attaching to receptors inside them. Stimulated by estrogen, the receptors activate genes that change how the cells behave. But in every organ system, the changes may be different.

Understanding estrogen's effects has been complicated by scientists' long-held assumption that the hormone bound to only one type of receptor, now called estrogen receptor alpha (ERa). The uterus boasts a high concentration of the alpha receptor, and since researchers thought estrogen was only important for female reproduction, they had no reason to go looking for a different receptor in other organs.

But in 1996, while searching broadly for new hormone receptors, Gustafsson stumbled on estrogen receptor beta. That finding turned the field of estrogen research around, says Kenneth S. Korach of the National Institutes of Health.

At the time, Korach was studying mice missing the alpha receptor. It had been a surprise that these mice could even survive. "The prevailing view was that you needed to have estrogen and you needed to have estrogen receptors," he says.

The discovery that there was a second receptor seemed to explain his results. If the mice missing the alpha receptor still had a functional beta version, their bodies still could respond to estrogen. At first, "everybody thought alpha was covering for beta and beta was covering for alpha," says Korach.

But when Korach bred mice lacking both receptors, the new mice survived too. "That clearly indicated that one does not need to have estrogen-receptor function to live," he says, "or for any type of developmental biology."

Though mice without the beta receptor can live, they are plagued by a list of health problems-a list that continues to grow as researchers observe the mice aging.

Bonnie Deroo, of the University of Western Ontario, in London (Canada), studies one impact of the missing beta receptor in female mice-fertility problems. Though these engineered mice can produce offspring, their litters are few and small. "Understanding how estrogen regulates ovulation may reveal causes of infertility in humans," she says.

Deroo's research focuses on estrogen in the ovaries, the female egg-producing organs nestled above the uterus. Ovaries, Deroo has found, have both alpha and beta estrogen receptors, but not in the same cells.

Deroo thinks the beta receptor may be involved in ovulation, the monthly release of an egg into a woman's uterus. Normally, estrogen produced by the ovaries causes the pituitary gland to release another hormone, called luteinizing hormone (LH) that directly triggers egg release. Deroo is trying to figure out what part of this cascade of hormones malfunctions in mice lacking beta receptors.

Korach studies this process to help women with infertility problems too, but he also points out another potential payoff from the research: estrogen receptor beta could be blocked in women as a form of birth control.

Cancer watchdog

Produced by plants, estrogen-like compounds called phytoestrogens are found in foods including soy and coffee. Some scientists have speculated that phytoestrogens played a key role in the lower incidence of prostate and breast cancers found for many years in Asian populations with soy-based diets.

RECEPTOR RATIO. Estrogen's varied effects in the body can be explained by the balance of two kinds of estrogen receptors, alpha and beta, in different tissues.
E. Roell/iStockphoto

This link doesn't surprise Gustafsson-the beta receptor responds to phytoestrogens much more potently than the alpha receptor does. Gustafsson thinks the beta version holds promise in combating cancer.

When estrogen binds to an alpha receptor, it usually signals the cell to start copying itself. This response is important in many situations, including making women's breasts and uteruses grow during pregnancy. But if something goes wrong while the estrogen receptor alpha is signaling the cell to multiply, cells may begin to grow uncontrollably and cancer could result.

"ERa seems to be, in that context, the bad boy or the bad girl," says Gustafsson. "But ERb is the watchdog."

Gustafsson's lab has shown that compounds that bind to only the beta receptor stop cells from multiplying. In mice, these drugs impede the growth of breast and prostate cancers.

Other labs studying the role of estrogen receptors in relation to cancer have found similar links in both males and females. Healthy breast and prostate tissues have more beta receptors than breast and prostate cancer samples, numerous studies have shown. Scientists have hypothesized that the lack of beta receptors in the cancer tissues allows the cancer to grow in the first place.

Compounds that bind to the beta receptor but not the alpha version, called ERb-specific agonists, also may be beneficial for a host of other health problems. These drugs, which turn on the beta receptor just as estrogen would, could even help patients survive severe physical injuries.

A paper published in the journal Shock in August 2000 found that females are more likely to survive traumatic injury, and less likely to go into sepsis-a severe bodily reaction to infection-than males. Scientists hypothesized that this finding could be because females have more circulating estrogen than males.

To follow up on this finding, another group of researchers gave estrogen or ERb-specific agonist to mice with lung injuries. In both groups of mice, the levels of inflammatory compounds in the blood instantly decreased.

The team, led by Heather Harris of Wyeth Research in Collegeville, Pa., also studied rats bred to develop inflammation in the joints, intestine, and skin. Scientists use these rats as models for human inflammatory diseases like rheumatoid arthritis and irritable bowel syndrome. Ten different ERb-specific agonists given to the afflicted rats decreased the inflammation and joint swelling.

Around the same time the link to chronic inflammation was found, researchers studying mice lacking the beta receptor noticed that the mice's immune systems weren't good at fighting off pathogens.

When the Wyeth scientists gave an ERb-specific agonist to mice infected with bacteria, more than 80 percent survived. No mice without the drug survived the infection.

Lessening the pain

For people with chronic diseases, ERb-specific agonists could also decrease pain, says Gustafsson. While no such pain drugs have been developed yet, clinical observations of women depleted of estrogen show a possible link between the hormone and pain levels.

One such observation comes from women being treated for breast cancer with aromatase inhibitors, drugs that stop the body from making estrogen. This means that there's no, or very little, estrogen to tell the alpha receptor to make cells multiply. But it also means there's no estrogen to bind to the beta receptor.

Aromatase inhibitor side effects include osteoporosis, which is thought to involve estrogen receptor alpha. But another side effect surprised doctors: Women taking aromatase inhibitors, such as Arimidex, reported feeling intense pain all over their bodies.

Now, based on experiments with mice, Gustafsson thinks the pain is linked to estrogen receptor beta.

"It seems that, generally speaking, ERb increases the pain threshold, that is, it decreases pain," says Gustafsson, "and ERa decreases the threshold, so everything hurts."

Put together, he says, the findings on the beta receptor's link to inflammation and pain mean that the next ibuprofen-like painkiller may be an ERb-specific agonist.

Based on his mice observations, Gustafsson thinks similar drugs could be designed as new anti-anxiety or anti-depression drugs.

When women reach menopause around age 50, and the amount of estrogen in their bodies sharply falls, many suffer severe depression. Gustafsson thinks this is no coincidence.

Estrogen receptor beta, after all, is plentiful in the brain. As embryos, mice develop beta receptors in their brains by the 12th day of growth. And adult mice lacking the receptor are violent and anxious, says Gustafsson.

"These mice attack each other," he describes. "They take the fur off each other."

In 2005, researchers led by Robert J. Handa of Colorado State University in Fort Collins performed a number of anxiety-related tests on rats treated with either ERb-specific agonists or ERa-specific agonists. When alpha was stimulated, the researchers found, the mice became more anxious, avoiding open areas in a maze, for example. The rats given ERb-specific agonists, however, showed none of these anxious behaviors.

From the moment he discovered the second estrogen receptor, Gustafsson says, he knew its function wouldn't be the same as the original receptor. After all, he'd isolated it from a rat's prostate, and estrogen hadn't been thought to have a function in the prostate. A decade of findings on beta receptors has strengthened the view that the second receptor has little overlap with the alpha version. It's also become clear just how many body functions the beta receptor mediates. The next challenge will be to find ERb-specific compounds that can bind to the receptor in certain organs but not others.

Hormonal origins

The evolutionary history of estrogen receptors may explain their wide range of functions. In 2003, a scientist studying mollusks discovered that these shelled organisms have only one hormone receptor (SN: 9/20/2003, p. 180), and it binds estrogen. When the scientist, Joseph Thornton of the University of Oregon in Eugene, analyzed the receptor further, he found that it's like a hybrid of the two human estrogen receptors. The discovery suggests that estrogen receptors must have been around early in evolution, before invertebrates and vertebrates diverged.

Gustafsson hypothesizes that this primitive receptor gave rise to the two estrogen receptors and, eventually, perhaps to more modern steroid receptors, including the glucocorticoid, vitamin D, and progesterone receptors.

"One can easily envisage that the estrogen receptors, being the first steroid receptors, must have had significant functions in regulating lots of systems in these early primitive organisms," he says.

Letters:

As I read this article, I was wondering whether the findings discussed suggest that a woman who has had both a hysterectomy and an oophorectomy should be on estrogen hormone therapy. Does a woman with no uterus or ovaries produce enough estrogen in other organs to benefit from the estrogen receptor beta?

Cathy Gregor
Alexandria, Va.

Almost all estrogen in a premenopausal woman's body is produced by the ovaries. "So after ovariectomy in women who have not gone through menopause, estrogen substitution is recommended," says Jan-Åke Gustaffson of the Karolinska Institute in Stockholm. But in older women, whose ovaries no longer produce very much estrogen, studies have shown risks to estrogen replacement. One of these-an increased incidence of uterine cancer-is obviously not a concern if the woman has no uterus. But others, including an increase in stroke and breast cancer, must be carefully considered by a woman and her doctor. In the future, the development of drugs that bind only to estrogen receptor beta in certain tissues may allow women to reap estrogen's benefits without these risks.-Sarah C. Williams

Jule, yes there is a number where they want es levels on us.I believe we may have no higher than 27 or 29.Two digit, anyhow.

And PUHLEEEEZE dont say it doesnt matter if we take tasmox or not.Because that scares me.I will go so far as to say it matters LESS, if our es values are 9.(There is a woman at the other site whose es level is, I think 7.She wants it to be ZERO.

To me, it's like being anorexic!)

The big reason I quit tamox is that it gave me a discharge, and I do NOT want to go from the breast frying pan into the gyno fire.

But remember--I had 9 for es value, I'm older than dirt, I was on AIs for almost 4 years, and my ONC, who drove me through 4 years of HT, said it would be OK.

Love to you, j

Lioness, I have a water filtration system too.Because bottled water is another twisted road to walk.Some bottled waters are tested & found to be TAP WATER!

And even real spring water--if it isnt in clear, heavy plastic, there is leeching of plastic chemicals into the water.The opaque plastic bottles do this.

I hauled gallons of Poland Spring in clear bottles all through my chemo, and for 2 years after.Until I bought a condo and had a SmartWater system installed on my kitchen sink.

It is cheap--under $100.You get a little seperate faucet which pours your clean, lovely filtered water.

Every 6 months or so, you replace the cannisters.

Home Depot.

It's MUCH cheaper than a whole house system.Everyone who sees mine gets one, ncluding my plumber!

Cheers!

Amy, it was Femara, but you are so wise not to turn tail.MOST women dont have these extreme results!

I hate drugs and..drugs hate me!

Plus, I get the impression that you are younger.Younger women do MUCH better on the AIs, because they're  not already not estrogen depleted by menopause.

EVEN you young'uns who are in medical menopause.Cant fool Mother Nature!There is still lots of free estrogen in your bloodstream!So dont worry, be happy!

Every time I give my rant, I remind people that I am 66.I was 12 years beyond menopause when I was DX!So the chemo and certainly the Femara took every grain of my estrogen!

How different is that from a girl in her 40s or even 50s, who is now in medical menopause?

I honestly think you'll be fine!Hey even I sailed along pretty well for the beginning years.Femara is a GOOD drug.

And Jule, have you tried melatonin for sleep?On femara, I got some nasty insomnia.First I couldnt fall asleep, the tossing and turning thing.

Then later, when I finally did fall asleep, pain woke me up.I had to roll to other side.

My onc suggested "Anything w/PM in he name" So I got some Tylenol PM.It WORKED!I downgraded to storebrand PM stuff.

So next  developed a HORRIBLE case of dry mouth!Girls here said "PM meds are nothing but BENEDRYL!They dry you out!!"

Took me ages to get my mouth undry again.Months.

So Edge, who was here then, suggested melatonin.

It is totally unlike sleep drugs!It actually is a hormone, but--get this--it 's GOOD against bc.In large doses(200 mg) it's protective!

Well I only take 2.5 mg before bed.I do it still because I dont want to find myself rolling again.

The drug is sublingual.You disolve it under your tongue.By the time it has dissolved, my eyes are closing!And when I get in bed, like a dog , I FALL ASLEEP!Deeply!Wow!Try it!

Mine's Nature's Way.Tablets take longer to work than sublinguals.

The other thing about sleeping is, we have to court the sandman.Nice cool room, quiet, and DARK!!I have read even light from clocks can disturb the melatonin (natural or OTC)from working!So--dark curtains that block any street lights.And I actually have a nice wonderful sleep mask called "40 Blinks" It is convex over the eyes, so you can, yes, blink and move your eyes in REM.

You little sisters are the reason I'm here.The women at BCO helped me through my TX and now I am here to give back--help the little sisters with my experience.

love, joan

Amaya, I took Femara for almost 4 years.I started right when I started rads.

My onc draws for lfts each time I see him.

I have never had a risen ALT or any other liver function value.

!!

It may be because I hate drugs and after chemo absolutely refused any other prescription drug but femara.No "antidpressant", no SLEEPing drug,no PAIN drugs.

I'm obsessed w/my liver ever since I asked my onc why, with 1 hot node bringing my grade to only type 2, I needed chemo.And he said "We dont want you presenting in 6 months with a liver mass."

YOW!! Shut my mouth!

I never complained about chemo, and once done I never took any prescripton (or NSAIDS!) again!

CAM I do a lot of.Maybe all the extra antioxidents help too.

So that is my experience.

I HAVE seen women have raised lfts.They come down when they quit extraneous drugs.

Good luck!I think things will be fine! 

I never had a drop of Neupogen.I had Neulasta all through my Cytoxin and then through Taxotere.

I dont believe there is a connection.My onc said the bone pain (Not Joint Pain as from femara!) was from r=the new blood cells that Neulasta makes, bursting, as it were, out of the bones and into the blood.

Ilene Dear One, they werent meant as kind words but as true words.You keep on, Brave Warrior.You are soooo needed and loved.

Ilene, I love your tamox idea.I hope you continue with it!

Lots of love to you, j

Hi Adele,

I'm here.I know you dont like my answers, but this one is a little better.

Oh definately!I MUST walk (hobble, gimp, schlep, totter) I walked 2 miles in 1/2 hour for years, with my Labrador way before all THIS.

And my body is so accustomed to exercize outdoors that it is the only thing that makes me feel good.

And me, too, nothing does ANYTHING for this femara belly and extra weight.

BUT!It is true that a lot of AI weight is water weight.I got edema from the steriods with chemo, and have been swelling ever since.Because Femara gave me horrible edema, on TOP of the steriod edema.My shoes havent fir me since I began chemo almost 5 years ago!

Ugh, last summer on femara I had to wrap my swollen legs in elastic bandages, on terrible days.

Water makes the face swell, and the belly swell too.

Not saying that's all it is, but there IS edema involved.And after 3 months OFF, I am actually starting to lose the water.

Who knows what will happen when it gets hot & humid, but for now...things are good!

The other hopeful thing is that as we regain lost muscle mass, we will burn more calories at rest again.Never like 16 year olds, but not like 90 year olds, all muscle-wasted, either.

So here's to every day, in every way......getting better and better!

BTW:Dandelion capsules are very helpful for water weight.

I take 1 3X a day.This is a tiny dose, but one I can live with.Otherwise you run into waking at night to pee, being unable to leave the house for more than an hour...(If you can take that, go for 2 or 3 ,3X a day!)

My onc did try me on Lasix, but it did nothing for me.<sigh>