Why aiming for female levels is incorrect

[KayXo]

To try and aim for female levels (to compare us to ciswomen) is wrong in three ways.

First reason being that women develop during puberty when growth hormone levels are high. Our growth hormones are much lower.

Second reason being that our androgen "load" is lower. Pre-op, doctors often aim to for testosterone levels in female ranges BUT most of the time, this does not tell the whole story. If we take estradiol orally, SHBG is quite high, higher than that of ciswomen getting estradiol internally because oral estradiol increases SHBG much more. So while our total testosterone might be in the range, our bioavailable (and free) testosterone might be much lower. Also, often, we take an anti-androgen which blocks androgen (and also further increases SHBG!). So, even if do actually measure free or bioavailable testosterone and it matches ciswomens' levels, part of that testosterone measured in the blood (serum) is actually blocked while it is not in ciswomen who take no anti-androgen. So, on the whole, we end up being LESS AFFECTED by androgen than women, having a lower androgen "load" as I like to call it. Lastly, some also take dutasteride/finasteride (an alpha-reductase inhibitor) which reduces conversion of T to DHT. Thus, despite matching levels of T with ciswomen, we have much less DHT in our tissues than them, further reducing androgen effect, and androgen "load". Post-op, transsexual women usually have lower T due to only adrenal production vs adrenal+ovary production in ciswomen AND some may have even less androgen "load" due to finasteride/dutasteride, as explained before. All this having been said, we can pretty much state with 100% confidence, that for the vast majority of us, in whatever phase of our transition we might be, our androgen "load" is less than those ciswomen we compare our estrogen levels with. Given the lower androgen "load", we need something to replace it with, namely, estrogen. More estrogen than ciswomen because we have a lesser androgen "load".

Third reason being and related to the second reason is that if we take estrogen orally, SHBG will be higher in us than in them. So, even if our (total) estradiol levels match, more of our estradiol is bound to SHBG and is unavailable. Free estradiol is rarely measured.

For all these reasons, comparing our estrogen levels (and even testosterone levels) to ciswomen is not useful. We probably need much more due to our lower androgen "load", lower bioavailable estrogen if we take estrogen orally and lower growth hormone levels. Doctors don't realize this unfortunately but they must be made aware of this.

[Danielle Emmalee]

Interesting information.  I'll be sure to keep it in mind.  Do you have sources for all of this?  It does seem to make sense but I'm sure a doctor would want to know where the info is coming from not just, "I read it on a website"

[Hikari]

Sure you could be right,your reasoning seems sound to me, but...

Doctors are not going to just take your word for it. In the absence of proper studies, or guidlines from health organizations (IIRC WPATH doesn't really give specific HRT instructions); they are going to go with what either worked for other medical professionals or what makes sense to them.

My point is, even if I am self medding with doctors supervision, generally speaking none of them are going to be comfortable if I take it out of the natural female range. Maybe even they would decide it is too dangerous and stop agreeing to supervise. This wouldn't be helpful.

So if you really believe like this then what you should do is gather your available evidence and ask for a local clinic, doctor, or university to their own study to see if indeed the ranges could benefit from being higher. Most doctors would love to see their name published in a medical journal so I am sure you can find someone with some interest.

[KayXo]

All of what I have said is based on fact that no doctor would dispute. So, if you bring these arguments to any doctor, they should agree. It's based on steroid hormone physiology, how different drugs we take work. Just show this to doctors, they will understand.

As to levels being measured to ensure that risk is kept to a minimum, this is based on the assumption that the higher the level, the higher the risk. If that were so, then four things contradict this assumption.

First, pregnancy. Pregnant women typically reach levels of 40,000 pg/ml (x 3.671 in pmol/L), up to 75,000 during the third trimester. They do not appear to be dying left and right. The worldwide population is still growing, often in places where hygiene is less than optimal (third world countries). Our species is clearly not on the decline. http://cebp.aacrjournals.org/cgi/content-nw/full/12/5/452/T1

Second, in men who have prostate cancer, who are at an advanced age, high estrogen doses are prescribed, in many times more than what is typically prescribed for us. Yet, studies have found no complications and indeed, an increased protection from thrombosis.

J Urol. 2005 Aug;174(2):527-33; discussion 532-3.

Transdermal estradiol therapy for prostate cancer reduces
thrombophilic activation and protects against thromboembolism.

"These results suggest that transdermal estradiol reduces thrombophilic activation in men with advanced prostate cancer, and protects against the risk of thrombosis."

Third, from this study is stated

Am J Obstet Gynecol. 1993 Dec;169(6):1549-53.
Fibrinolytic parameters in women undergoing ovulation induction.

"Down-regulation of the fibrinolytic system was observed as estradiol levels increased. However, thrombin formation did not change, thus suggesting that elevated circulating estradiol alone does not predispose to a thromboembolic event."

Lastly, despite very high doses of estrogen prescribed in the past to transsexual women and prostate cancer patients, from the 1960's to the 1990's, very few breast cancer incidences have been noted either by urologists, Harry Benjamin himself and Gooren's team in Holland, international recognized. Also, no liver complications were noted by Harry Benjamin.

[KayXo]

Further to my post, I would like to add other reasons...

Our levels are only taken at one moment in time, where if we took more blood tests, we would perhaps find out that our levels sometimes go below range or above range due to fluctuation in levels, especially in the case of sublingual and injectables.

Also, levels fluctuate so much during a woman's menstrual cycle that the range is pretty wide and makes aiming for that range pretty much useless. Where do we do we decide is a good level for us, how do we narrow it down to a smaller range? Take an average? And have we actually determined that on average, ciswomen or transsexual women feel best within that chosen, average range? Perhaps they feel best at a higher level and perhaps it even varies among women such that some feel good at lower levels while others not so good and feel better at higher levels? What about sensitivity and individual variation? There is surely no way we can measure that.

Finally, on average, we are heavier, weigh more than bio females (as was brought to my attention by a very observant girl) thus probably requiring higher levels for the same effect. 

All these things taken together, we have a pretty good case, I think, in persuading our doctors that we probably need higher levels than ciswomen, if the case may be (and not suggesting that you increase your dose if you are doing well at the moment) and that taking our levels isn't very useful. 

You can bring this to your doctor's attention. As always, consult your doctor with any change you make. Let me know what your doctor thinks, if you do.

[mrs izzy]

I think you are trying to push the more is better idea.

This has been brought up so many times in the past. What has been found is that NORMAL is a SAFE range.

Many always think more is better and things will be faster, does not work that way post-puberty.

Now if you are pre-puberty and start HRT you will have a way better response to cross hormone therapy.

Relax, stop over thinking all of this and stay safe.

Isabell

[Randi]

Kay, I think you decided that more is better and sought out evidence, primarily from your own thought processes, to back up that decision.

Why do you think there is any benefit from increased doses of estrogen?   There are only a finite number of estrogen receptors in the body.  Once they are all activated by the estrogen molecule, there is nothing remaining to be done.  The extra estradiol will convert to the weaker estrone and SHBG will bind up the rest.

Randi

I think you are trying to push the more is better idea.

Isabell

[KayXo]

I'm just stating that first and foremost, there is no such thing as a normal female level since in genetic females, levels vary so (too) much during a menstrual cycle. Secondly, that comparing our levels to theirs is like comparing oranges and apples because of our unique situation and different growth hormone levels. Third, that because of several variables, our needs may be different and as such, it is possible but not absolutely imperative that we need higher levels. I'm not overthinking this. I'm stating what seems to be quite obvious to me, and what came to my attention after I personally experienced less than optimal results on lower doses which seems to be the case in quite a number of other girls but certainly not all.

It's important to make this known to not only other girls but to doctors as well so that all of us can get the treatment we truly need without compromising our well-being or safety. So that we don't base ourselves on numbers that don't seem to mean much if we take everything that I have stated above in consideration.

[KayXo]

There are only a finite number of estrogen receptors in the body.  Once they are all activated by the estrogen molecule, there is nothing remaining to be done.  The extras estradiol will convert to the weaker estrone and SHBG will bind up the rest

Is there any science behind your statement? Has it been shown?

If that were in fact the case, then why do increased estradiol levels in pregnant women, well beyond the levels we ever reach, up to 75,000 pg/ml, occur and why do they result in increased breast growth, increased scalp hair growth, thickness, and have several other effects? If indeed, there were a finite number of estrogen receptors, then we should not expect such high levels of estradiol during pregnancy, we should expect it was a waste and wonder why nature would make such a mistake. We should expect much higher estrone levels relative to estradiol, which isn't the case and we should expect no more effects than before, which again we don't. We see increased effects from increased levels.

One could argue that women are different than us. But, one just needs to point out those studies in prostate cancer patients, males at an advanced age who are prescribed estrogen doses well beyond what we take in most cases. Such high doses are prescribed because lower doses aren't as effective and just go to show that in males, as well, higher level do make a difference and there is no such thing as finite receptors, otherwise, higher doses wouldn't be prescribed.

Receptors aren't a constant either. They have a limited lifetime, are constantly renewed and synthesized. So, at any given time, you might have more or less, depending on hormonal "milieu", environment.

[KayXo]

Furthermore, based on the previous explanations, I'm prone to thinking that oral administration of estrogen, even if bio-identical and considerably less risky is not optimal for us.

Oral estrogen tends to increase SHBG. SHBG binds to androgen more strongly to estrogen. With this increase in SHBG, you are further reducing androgen which increases your need for estrogen.

Can the levels gotten from oral estrogen meet those needs for higher estrogen? Perhaps not, because firstly, since SHBG is increased, more estrogen will be bound and not available and more importantly, you will mostly get from oral, estrone as opposed to estradiol which is less potent in terms of estrogen receptor activity. Hence, for these reasons, your needs for higher estrogen might not be met.

Non-orally, SHBG is much less pronounced and elevated. Estradiol levels are also higher relative to estrone. Hence, you affect androgen much less and get more for your buck in terms of estrogen.

[mrs izzy]

I think you are trying to push a snowball up hill in the middle of summer.

Cross hormones have been used for many, many years now. There are know medications that work and others are just the old placebo effect.

I truly wish you luck and hope you can find a doctor that will help you get where you wish you can get.

Isabell

[KayXo]

By no means am I advocating that anyone self-medicate or increase their doses if things are going well for them at the moment or do anything without first consulting with their doctor. I've been careful with my statements and take everyone's health into strong consideration. I'm treated by a doctor who works together with me and who trusts my judgment when it comes to hormones. I've been under his care since 2005. He's our family doctor. He takes the time to listen and I consider myself very lucky to have him in my life. I am planning to see other doctors in my area to discuss with them HRT for transsexual women after discussion with a psychiatrist who treats transgendered girls. He suggested I do this and agreed that my reasoning behind much of what I said was sound.

There is much to be learned in this very narrow area of endocrinology, not taught at medical school, where guidelines in TS hormone treatment are still quite vague. I have spent years educating myself with scientific studies, I have been on hormones for almost 10 years, and I have spoken to hundreds of girls worldwide so I am aware of their concerns, the problems, and various treatment protocols in the world. So, I think my knowledge can benefit others like me who are less informed, doctors who don't have the time to educate themselves as much because they have so much to read, so many patients to treat. This is why I share this information with you. Not so you can follow my guidelines, ignore your doctors and do as you wish. But, so you can start to ask yourselves questions, become more informed, share with your doctors and optimize your treatment and that of other girls under his care.

I'm not advocating high doses, I'm advocating optimal doses for each and everyone of us and stating current weaknesses with today's TS hormone protocols in an attempt to improve treatment.

This is simply for information purposes to advance knowledge in this area for the betterment of our treatment. Read, question, share with your doctor. That's all I hope for. Nothing more. I strongly discourage doing things on your own. I'm also saying that perhaps, if you don't have good results at lower levels, there could be an explanation and you could share this with your doctor.

My word is not gospel. Take with a grain of salt, question it and discuss with doctors.

[Randi]

Orals less risky?  Where did you get that?  Non-orals, injections, gel or patches are much less risky than orals.  The first pass effect in the liver when processing oral estrogen is well known. In addition conversion of oral estrogen to the weaker estrone is well established.

I agree that non-oral estrogen is safer and more effective.

Furthermore, based on the previous explanations, I'm prone to thinking that oral administration of estrogen, even if bio-identical and considerably less risky is not optimal for us.

[Jenna Marie]

My endo doesn't even bother testing E levels, and I'm comfortable with that; she says she doesn't want to chase lab values at the expense of the patient. She tests free T and monitors the other major lab values which are indicators of health. However, she also tries for the minimum effective dose, which is my personal preference after my scary experience.

I started off on a dose, via patches, that is much lower than is usually recommended... and within 2 months was showing signs of liver damage that abated once I was taken off HRT. (I was eventually able to resume at half the initial dose, which has worked beautifully for me so far.) So I have no question whatsoever that for *some* women, there are definitely risks to increasing the dose, and there's no real way to find out if you're in the group who's sensitive enough without taking the chance. I myself will NEVER suggest that more = better results. Once you've gotten enough E to achieve your goals, more changes nothing except the risk profile.

[KayXo]

I meant to say that oral bio-identical estrogen is less risky than oral Premarin or especially oral ethinyl estradiol. I should have elaborated. My fault!

Since bio-identical estradiol is native to the body and is quickly eliminated from the body, its effects on the liver and especially on coagulation factors is much less. This is why I personally consider oral bio-estradiol quite safe, especially compared to other forms of estrogen.

The effects of ethinyl estradiol have been established to be about 500-2000x times those of bio-identical estradiol on liver. If you translate this in terms of how much is prescribed to women worldwide when birth control pills are taken, you get alot!

I agree that non-oral is safer for the reasons you mentioned but when it comes down to bio-identical estradiol, the  increased safety is not that much at least at the doses we typically take.

[KayXo]

I started off on a dose, via patches, that is much lower than is usually recommended... and within 2 months was showing signs of liver damage that abated once I was taken off HRT.

What signs?

[amZo]

I started off on a dose, via patches, that is much lower than is usually recommended... and within 2 months was showing signs of liver damage that abated once I was taken off HRT.

I assume you're referring to an 'unusual' blood test for liver function? If so, I doubt a low dose estrogen patch caused any liver damage. The liver is an amazing organ, mine appears to have super human strength. It hates me I know that much. 

I find this topic very helpful.

[Jenna Marie]

Yes, it was a severely abnormal liver function test, after which I had an ultrasound that showed "transient liver damage." I dunno, I'm inclined to trust the experts who said it was the high HRT causing it, particularly since thereafter the liver recovered once the dose was first removed and then lowered. (I'd had a baseline panel done beforehand, too, and there were no other apparent causes; she ran some other tests to check on other possibilities but it was years ago and I don't recall what she did, only that it came back negative for any other possible issues.)

The final conclusion is that I'm just very, very responsive to estrogen, because in addition to the "overdose" signs, I've been on a dose solidly within the range of what's provided to cis menopausal women and I've had fantastic results.

[KayXo]

I doubt it was due to the patch for two reasons. First, that very little estrogen taken transdermally makes it to the liver and secondly, that you were taking a low dose so that very, very little would make it to your liver. Pregnant women have very high levels for 9 months and don't have liver damage from it. Even in prostate cancer patients who are on a high dose transdermal treatment of estrogen, much older than you and sick, no liver complications arise. And I could cite many other examples.

Must have been something else or an error or something. I've never heard of any transsexual woman having liver problems from transdermals, ever. I believe what you are saying, don't doubt you for a second but something is off.

I do also know that your situation is quite unique in that your baseline T levels were quite low to begin with and that you developed DD breasts on a low dose of estrogen, lower than what is typically prescribed as you seem to state in your posts. Maybe you have a genetic condition, aren't XY, something? Don't know...

[Thylacin]

I doubt it was due to the patch for two reasons. First, that very little estrogen taken transdermally makes it to the liver and secondly, that you were taking a low dose so that very, very little would make it to your liver. Pregnant women have very high levels for 9 months and don't have liver damage from it. Even in prostate cancer patients who are on a high dose transdermal treatment of estrogen, much older than you and sick, no liver complications arise. And I could cite many other examples.

Must have been something else or an error or something. I've never heard of any transsexual woman having liver problems from transdermals, ever. I believe what you are saying, don't doubt you for a second but something is off.

I do also know that your situation is quite unique in that your baseline T levels were quite low to begin with and that you developed DD breasts on a low dose of estrogen, lower than what is typically prescribed as you seem to state in your posts. Maybe you have a genetic condition, aren't XY, something? Don't know...

Why do you doubt it was due to estrogen when this was a conclusion reached by doctors who were actually monitoring her and doing tests?