Insensitivity to estrogen from too high dose?

[teeg]

I heard from a peer who's also transitioning that on too high of a dose of estrogen, the estrogen receptors in the body can become insensitive to the high amounts of estrogen. However, they are self-medicating, so I doubt the authenticity of their claims.

While I won't mention the actual doses, I will say that my first Endocrinologist moved me from a conservative dose to a relatively high dose without concern for any sensitivity/insensitivity. I asked my second Endocrinologist about this insensitivity topic, and they directly told me that it was false, and, "it doesn't work like that."

I plan to discuss it in further detail with my first Endocrinologist who prescribed me the higher dose, but while I wait for an appointment with them, does anyone have any experience and insight into if insensitivity to too high of an estrogen level is even true or not?

[KayXo]

It's false. If that were the case, then how to explain the increased breast growth and other effects caused by increased estrogen during pregnancy, with levels typically in the 1,000-40,000 pg/ml range, up to 75,000 pg/ml in the third trimester. Why would the body even increase its estrogen (or progesterone) production during pregnancy if it didn't make a difference or worst, caused estrogen insensitivity? The pregnant body needs estrogen, and more of it! Prostate cancer patients need high levels as well because lower levels do not cause enough androgen suppression and if high levels didn't make a difference or worst, caused estrogen insensitivity, then higher levels wouldn't be effective or be prescribed in the first place. Same with transsexual women who, for some, noticed increased feminization from higher doses, sometimes quite high by our standards.

I think that probably estrogen receptors do decrease but not so much as to make no difference vs. before  on a lower dose. But enough so that the change from low to high is not as abrupt but more gradual.

[mrs izzy]

Dose of estrogen is gauged by your levels in your blood test.

I would say less is always better but at the same point you want to get some effects of the HRT.

I would trust my Endo before anyone who is DIY.

I always asked my GP what, where,why and when it came to dose changes.

Sometimes we way overthink things and just need to relax. Nothing happens over night and it takes YEARS for the full effects to be seen. You will be on estrogen all your life.

Isabell

[Ltl89]

Not sure, but I suppose it depends on the dose.  In any case, lower doses had minimal effects on me and Ive been responding well to a higher dose.   So, I wouldn't worry too much about a higher dose not having any effect because my e levels trippled from a dose increase. Then again, I've since learned that my current dose is considered average or only a little higher depending on who I talk to.  I think the goal is to find the lowest dose that works for you (usually for safety reasons) and allow it the time to work.  I can't talk about dosages here, but I wouldn't worry if it falls somewhere in normal ranges and doesn't appear insanely high.  In any case, my knowledge on hormones is mainly from personal experience, so I don't claim to be an expert on this.

[sad panda]

Only way that could happen is it could raise your SHBG which is temporary.. o.o

[KayXo]

SHBG binds androgen (DHT especially) more strongly than estrogen. So while it may increase, especially with oral intake, it will preferentially bind to androgens, thus having an anti-androgenic effect in the process, helping E work better.

[Gina_Z]

Jennifer Diane Reitz suggests here: http://transsexual.org/letters32.html#noeffect
that taking too much estrogen can result in the production of androgenic mimics, by the liver.
(Transsexual.org) Valid idea?

[KayXo]

False. If that were in fact the case, imagine the repercussions on pregnant women whose estrogen levels skyrocket (increased masculinization) or even on the fetus! OR the consequences on prostate cancer patients who are given very high doses of estrogen to SUPPRESS ANDROGEN...And I'm sure we would have already heard the terrible effects on transsexual women of high doses of estrogen, trust me! The last thing we want is increased masculinization and if that happened, it would have been known long ago. Back in the old days, doctors would prescribe doses unheard of today to transwomen and nothing...no such problems.

To also add to this, estrogen cannot convert to androgen, EVER! Only androgen can convert to estrogen.
http://www.angelfire.com/sc3/toxchick/images/S/steroidogenesis.gif

[Gina_Z]

Someone should educate Jennifer!!

[Ms Grace]

It might depend on what is meant by "too much"...our endos will (hopefully) always keep us within a safe range, as will the body of a pregnant cis woman. A DIY trans person might significantly overdo it thinking that if x amount yields a particular result then ten times x will be even better! There has to be a point where too much is too much and the body works to shut it down? Just a thought not based on any scientific knowledge whatsoever.

[KayXo]

Even if we try, we won't even ever approach those levels reached during pregnancy or ever take the doses prescribed to prostate cancer patients. In both cases, the body doesn't shut it down.  So, I very much doubt that keeping us within a "safe" range, which varies from one doctor to another (thus arbitrary), is valid. Based on what? Studies that have found complications in women taking ethinyl estradiol, premarin, provera, all of which we don't take?! We take bio-identical estradiol, found to work differently, be safer. If you take it non-orally, even better as this route has shown to have a negligible effect on hepatic parameters with the use of bio-identical estradiol. One just needs to look at facts, at the many studies that have come out in the last two decades and so on, to realize this simple but often overlooked fact. Do your own research, read entire studies, talk to scientists, doctors and you will find out for yourself. Keep questioning and differentiating fact from false claims. Don't take my word...go out there and find out! 

I'm not saying that everyone should take a high dose but that if needed, one can, with their doctor's supervision and permission, up the dose to achieve more adequate results to a degree that is greater than what is "believed" to be safe. One simply needs to be well informed, have an open-minded, well-versed doctor for that to be possible. But, I always encourage the lowest effective dose which varies from one person to another so that a higher dose may not be necessary at all! If things are good at a given dose, then there is no reason to change anything...and to increase dose just because one thinks it will be even better is immature and childish, I agree with you...if it's working at the moment, then leave as is.

[PrincessDayna]

This is false, I am sure. I wouldn't say that high doses create reverse effects.
Im on high doses of estradiol valerate, im, from my endo. Im also on a few other things, being intersexed, but to combat and possibily reverse some efects of virility I am on a very high dose of estradiol, to put it bluntly. I won't say it feminized me but it has pushed back a ton of virility. Everytime I get labs the results read as if I am pregnant. Three monthes in I was at 5k+ ng/dL, e2 and it has since risen.
I guess my point is everyone is different, needs different, and the person to know best asside from you is a competent endo. I am sure if my med doses were replicated by a mtf they may get a bit moody, could even be risky/hazardous.
The thing is the reason a pregnant woman has such high kevels asside from the obvious is the body uses it. The main thing is it protects fetal development from androgen levels that can occur. Can, not does.
The same as prostate cancer patients. The body uses it.
All bodies are different, and have differing needs. I suppose exogenous is a bit safer in higher doses then ingested pills but only due to liver break down of the hormones.
Most studies that are used for modeling doses are outdated or limited, and many fears revolving around estradiol are due to estrace, from mares. Anyhow, ask your endo why. Make a list of concerns for each visit and discuss them. Many people do not do this and you woukd be surprised at the answers given.

[KayXo]

Three monthes in I was at 5k+ ng/dL, e2 and it has since risen.

You mean pg/ml, no? Mine are around 2,000 pg/ml on day 4 after injections. Levels do fluctuate on IM (intramuscular) injections so are higher on days 1 and 2 then start to go down until day 7-8 when levels significantly start to drop, according to one study. When do you have your blood drawn?

I take my injections every 5 days now so levels must have probably risen somewhat. I feel great! Best I felt in 8 yrs since SRS. All that time, I was on oral, sublingual, rectal and transdermal estradiol.

I am sure if my med doses were replicated by a mtf they may get a bit moody, could even be risky/hazardous.

Maybe, maybe not. We really don't know. Pregnant women have levels that go up to 75,000 pg/ml, but with average levels ranging from 1,000-40,000 during the whole course of pregnancy.

http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf

"If conception occurs, estradiol levels continue  to rise, reaching levels of 1,000-5,000 pg/mL during the first trimester,  5,000-15,000 pg/mL during second trimester, and 10,000-40,000 pg/mL during third trimester. 6-8"

The thing is the reason a pregnant woman has such high kevels asside from the obvious is the body uses it. The main thing is it protects fetal development from androgen levels that can occur.

Why do you assume the body in transgender females wouldn't use it? Seems my body has responded quite favorably to a jump in levels from injections. Based on this study, in pregnant women just before delivering so at the peak, androgen levels were on average 184 ng/nl which is still low BUT up to 921 ng/dl in women with males fetuses whereas it was up to 393 ng/dl in women with female fetuses. So, yes you are right! I din't even realize this until now, how high androgen levels could get during pregnancy...wow! Either most of the testosterone only really affects the fetus as it remains in the placenta (?) or the high levels of estrogen compensate for the rise in androgen as you seem to have stated above.

http://cebp.aacrjournals.org/cgi/content-nw/full/12/5/452/T1

I suppose exogenous is a bit safer in higher doses then ingested pills but only due to liver break down of the hormones.

Exogenous means coming from the outside so whether we take estrogen by means of patches or pills, we still are taking them exogenously whereas in genetic women, estrogen is produced on the inside of the body (endogenously), by different organs mostly ovaries (and placenta, corpus luteum during pregnancy). I think what you meant to say was that when estrogen is delivered right into the blood vs liver before blood, it is safer. I agree. Because orally (ingested pills), estradiol in liver affects synthesis of proteins, factors involved in coagulation, increasing the tendency to coagulate (clot). 

many fears revolving around estradiol are due to estrace, from mares.

You mean to say Premarin (PREgnant MARe UrINe) not Estrace which contains the same estrogen that is produced by the human body, 17 beta estradiol.

[Hideyoshi]

I would trust my Endo before anyone who is DIY.

this

[teeg]

I would trust my Endo before anyone who is DIY.

Personally I wouldn't be too quick too ward against DIY medding. Since beginning my transition I've had three endocrinologists. Many times before I've found normal people like you and me who are much more knowledgeable than the average endocrinologist (at least in my area) in regards to transgender HRT. With oversight and routine health checks from a physician I'd be open minded to DIY medding, but again it's pretty risky, I wouldn't do it.

For example, I originally started taking Spironolactone as my anti-androgen. I switched to Cyproterone Acetate and a little while later my prolactin levels went up. We did a handful of tests, bloodwork, MRI. Did I have a tumor? Did I have other endocrine problems? I simply googled, "cyproterone acetate prolactin" and quickly found that the medication very often raises prolactin levels.

Recently as I've posted before I had a few blood draws taken at different times over the course of a couple months. One level was 400+, the next +-100, the last about 270. Again, many tests, many complicated theories, and I simply asked if taking it sublingually could make my dose spike after taking it and lower over the day since you're putting all of the pill into your blood at once.

HRT is just as serious as FFS, SRS, etc., in my opinion. I really wish there were really really good endocrinologists actually experienced in transgender HRT care (I've heard endos say this so many times and end up being pretty incompetent).