Hi calico,

Quote from: calico on January 27, 2014, 01:52:12 PM
The thing I am wondering is.... Where or what level do the endo's prefer or is preferred And is anyone in the 200-300+ range

It depends what measuring regime your 200-300 range is measured in. If it's pmol/L (pica mols per litre) then you tend to be in the lower female range. Implants spike me up to 2500-3000 pmol/L on insertion and gradually drift down to round 800 after about 12 months, then I get another implant.

I did know the formula for converting pg/mL, but have since forgotten. It's those bloody fluffy puppies from Grace that's done it.     

Huggs
Catherine

OK just got my T lvl back. It was 405, on the 21st. Not as low as I would like.

Hi Sheala,
I am still testing in the 400 range about half of orginal levels, and seem to have pretty good results with the E and progestin as far as mental and physical effects, I have not heard back from my endo yet to adjust anything, not pushing the issue but I did just find a new doctor who seems to have a bit experience working with tg/ts folks so hoping to switch over and get better support on my Metabolism.
Jerri

That's something that confused me. My gyne didn't want any pre levels. I almost had to demand the last. Her reasoning if I feel good about there is nothing wrong. Granted I agree to an extent however it doesn't work for everything and this is one that I would rather know.

Quote from: Ms Grace on January 27, 2014, 12:27:54 PM
Every time my endo tells me my levels my brain goes chasing after a fluffy puppy. I really should pay more attention I guess but the numbers mean squat to me. If my endo is happy then I'm happy. I am seeing him tomorrow though and will try to remember the numbers this time rather than letting them go in one ear and out the other...

Pretty much my reaction too. They're now well into in female range, works for me.

Got my results back, which were a little surprising / disappointing, but in any case, after 72 days on HRT:

Testosterone:
4.9ng/ml (-0.1 ng/ml from last test)

E2:
21 pg/ml (-16.4 pg/ml from last test)

It's particularly perplexing as the last test was pre-HRT and yet somehow my E2 level has fallen post-HRT. I'll definitely be speaking to my endocrinologist about this 

TBH unless you are getting SBG measured the T and E figures are pretty meaningless.

What's SBG? .. and if they're meaningless, why did my endo ask me to get them done, they're $40 each..

Levels are meaningless because they cannot tell you whether with your current dose, you are getting the results you want, like breast growth and other feminization. They also cannot tell you if you feel good or not on the dose. Levels fluctuate so much in natal women and don't coincide with optimal rate of development. Different women react differently and natal women developed at a time when growth hormone levels were at their highest, much higher than ours.

But, taking a quick glance at your levels anyways, one can readily notice that your estradiol level is extremely low but that your testosterone level is low too which is to expected if you are taking an anti-androgen. Don't forget that anti-androgens also block testosterone so tests cannot measure that.

SHBG is sex hormone binding globulin which binds more strongly androgens (i.e. testosterone) than estrogens, rendering them inactive, unable to act on receptors until they become unbound. Typically, it is increased with oral estrogen and to a much lesser extent with non-oral. I don't think it is necessary to measure. You could always measure free or bio-available testosterone to see how much is not bound to SHBG and how much is potentially able to reach receptors but also remember that your receptors are partially blocked by the anti-androgen you are taking.

The estradiol measured is free estradiol.

My GP is managing my HRT (very experienced and a Pharmacist as well) and requests total and free T, E and SHBG each time along with numerous others (paid for in full by Govt). My SHBG has spiked very high in the past pre HRT with a dramatic  impact on  free-T.  So it is a useful piece in the puzzle. What we don't do so much is over-analyse things. We hit normal female level of T straight away whilst E is a bit high. Given my age, the Doc is looking at other things like Cholesterol, BP and liver function. If I am unwell, he will act, otherwise we talk about general wellbeing. Impact on family etc.

It really does seem to be a lottery though with astronomical odds due to the huge number of variables we each bring to this.

So what if your free T is low due to high SHBG? If you feel good, and physically things are going well, then what more could that finding bring you. Would you really change things based on this result despite feeling and looking good?

What is considered a too high level of E? Why is that a problem? One study has shown that estradiol levels alone cannot predict health risks.

From 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."

Also, as far as liver is concerned, I'm assuming you, as most of us today, are taking bio-identical estradiol. And since your SHBG is high, it's probably oral. Consider the following statement from Harry Benjamin back in the 1960's:

"Close observation and repeated examinations are essential during treatment. Liver function tests may be
advisable, the so-called BSP (bromsulphtalein) being probably the most valuable. The liver is the organ that metabolizes ("digests") the estrogen and it is conceivable (although not actually shown) that it may be unfavorably affected by long-continued medication"

Consider as well that back then, only non bio-identical forms of estrogen were prescribed ORALLY and that doses were extremely high, Premarin and ethinyl estradiol daily and DES (Diethyl Stilbestrol). High doses of parenteral (injectable) estrogen were also prescribed, estradiol valerate monthly! And yet, liver was not shown to be unfavorably affected by long continued medication.

The potency of Premarin is up to 7.5x and Ethinyl's 500x that of bio-identical estradiol on liver function according to this paper CLIMACTERIC 2005;8(Suppl 1):3–63. Make your own deductions.

Also consider pregnant women whose levels typically range from 1,000-40,000 and up to 75,000 pg/ml. See http://cebp.aacrjournals.org/cgi/content-nw/full/12/5/452/T1. And yet, our species is still alive, more than ever. Women are making babies, left and right and aren't dying. Or having serious, potentially life-threatening complications every time they become pregnant.

And finally consider those men, at an advanced age, stricken with advanced prostate cancer, who are prescribed high doses of estrogen and   injectable estrogen. No thrombotic complications (or no more than would be expected in the normal population) are noted in these men and when doses are used, certain adverse cardiovascular non life-threatening diseases do occur but only in those with preexisting cardiovascular problems.

Are high E levels really as dangerous as doctors would lead us to believe? Facts speak for themselves.

One other objection doctors have is increased breast cancer risk. Do consider that no cancer had been detected amongst Harry Benjamin's hundreds of patients, none have apparently been noted in prostate cancer patients, both populations being exposed to very high levels of estrogen, none were reported by Gooren's team in Holland treating thousands of transsexuals since at least the 1980's, only 4 had been reported by the 1990's in the literature. It appears breast cancer is extremely rare amongst our community. And according to studies, we aren't at higher risk for other cancers vs the general population. In fact, much like genetic women treated with estrogen at menopause, the incidence of colon cancer is lower.

Even amongst natal women (and mice!), if one really searches and studies the question, one finds that the opposite seems to actually hold, that high estrogen levels seem to actually protect against breast cancer, slowing down or even shrinking tumor. If you want, I can provide studies to that effect but since we aren't natal women and the incidence is so rare amongst us, it doesn't really matter, I think, unless the doctor insists on seeing the evidence.

So, I ask again. Are high E levels as dangerous as doctors would lead us to believe? 





Edited for Dosages - DO NOT POST DOSAGES

"Are high E levels as dangerous as doctor's would lead us to believe?"

And another q' what about DVT? Suppose one is taking E in the least dangerous and more direct route (injectable's , patch) is one still susceptible to DVT, liver problems? How about oral as well?

Hi calico,

Much depends on what you call high E level. 2,000-3,000 pmol/L is not high. 5,000-10,000 pmol/L is definitely high and would need an immediate response.

Injection, patch, implant are by far the safest form of delivery with respects to DVT, but yes, DVT is still a risk. A build up of any chemical (calcium, cholesterol, fat, oestrogen, whatever) in the blood system will always contribute to Deep Vein Thrombosis.

Liver/kidney issues are manifested by oral delivery, as they are filtration system from the digestive to blood systems.

Huggs
Catherine

Pregnant womens' levels can go up to 75,000 pg/ml or 275,000 pmol/L but more typicallly levels of 15,000-40,000 pg/ml (55,000 - 147,000 pmol/L) during the third trimester of pregnancy. And yet no life-threatening complications such as DVT arise, or at least, very rarely. If high levels were so dangerous, then wouldn't we want women to avoid pregnancy since levels increase so much. If they were so dangerous, wouldn't we expect more deaths resulting from pregnancy, less births, a more steady or declining population in the world; in fact, quite the opposite is taking place...the world population is increasing steadily, often in places that have poor hygiene and poor conditions, and in poor families.

Consider that, as I've mentioned above, thousands, if not more, of transsexuals took much more potent forms of estrogens in very high doses from 1950-2000 and yet, they also weren't dying left and right from liver complications. Even the infamous Harry Benjamin states that liver dysfunction hadn't been shown as of yet in transsexuals being prescribed the notorious DES or Ethinyl Estradiol in doses unheard of today.

Consider that millions of women are prescribed birth control pills that contain Ethinyl Estradiol, 500x more potent (according to a Swedish report, up to 1500x) than bio-identical estradiol (what we take) in terms of effects on the liver. Are birth control pills banned? Are girls on pills dying left and right?

We are taking a much safer form of estrogen, much much safer. So, even if taken orally, where it passes through the liver and affects clotting, it is nowhere near as potent as these other forms which seemed to only somewhat increase risks. Bio-identical estradiol is also quickly eliminated from the body.

Non-orally, there is barely no risk in terms of DVT or liver complications if bio-identical estrogen is taken. Several studies have shown this. Just take a look on pubmed.com. Prostate cancer patients given high doses of patches or injectables, much higher than those typically prescribed to us did not experience any complications. And this was in men at an advanced age stricken with cancer! Reread my post above, in detail.

Even in women who had advanced breast cancer, very high dose oral estradiol was given for a period of 6 months and yet only 1 suffered from thromboembolic complications in a sample of 32 women and it occurred in a woman at an advanced age with Grade 4 cancer, the most advanced.

If you really read between the lines, take the time to do your own research, you will realize how negligible the risk of DVT or liver complications is with bio-identical estradiol, taken orally or not. Non-orally confers a very slight advantage in terms of risks when it comes to bio-identicals.

Progesterone isn't associated with any of that either, quite safe as well.

Quote from: calico on February 03, 2014, 03:23:10 AMAnd another q' what about DVT? Suppose one is taking E in the least dangerous and more direct route (injectable's , patch) is one still susceptible to DVT, liver problems?

Tidsskr Nor Laegeforen 1993 Mar 10;113(7):833-5

Endocrine treatment of prostatic cancer. A renaissance for parenteral
estrogen.


"Oestrogens, administered per os may have serious side
effects, in particular thrombosis and cardiovascular complications.
If the oestrogens are administered parenterally, changes in liver
function can be avoided and risk of side effects markedly reduced."

"We can sum up our own experience as follows: Plasma
testosterone is reduced to castration level after 2-3 weeks. Liver
function, evaluated by the sexual hormone binding globulin level in
plasma, remains unchanged."

" Follow-up of the patients does not indicate any increased risk of thrombosis or cardiovascular
disease."

Prostate 1989;14(4):389-95

Estrogen therapy and liver function--metabolic effects of oral and parenteral
administration.

"Oral estrogen therapy for prostatic cancer is clinically effective
but also accompanied by severe cardiovascular side effects.
Hypertension, venous thromboembolism, and other cardiovascular
disorders are associated with alterations in liver metabolism. The
impact of exogenous estrogens on the liver is dependent on the route
of administration and the type and dose of estrogen. Oral
administration of synthetic estrogens has profound effects on
liver-derived plasma proteins, coagulation factors, lipoproteins, and
triglycerides, whereas parenteral administration of native estradiol
has very little influence on these aspects of liver function."

Prostate 1988;13(3):257-61

Cardiovascular follow-up of patients with prostatic cancer treated with
single-drug polyestradiol phosphate.

"Thirty-eight patients with cancer of the prostate were treated with
strict parenteral estrogen in the form of monthly polyestradiol
phosphate injections"

"In contrast to studies with oral estrogens,
there have been no cardiovascular complications at a mean follow-up
of 12.9 +/- 0.7 months (SEM). Twenty-nine of the 38 patients (76%)
have responded to therapy."

Cancer. 2005 Feb 15;103(4):717-23.

Phase II study of transdermal estradiol in androgen-independent
prostate carcinoma

"The authors tested the safety and
efficacy of transdermal estradiol (TDE)"

"Toxicity was modest and no thromboembolic
complications occurred. The mean (+/-95% CI) serum estradiol level
increased from 17.2 pg.mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL
(range, 334.6-586.7 pg/mL)."

"No change in factor VIII activity, F 1.2, or
resistance to activated protein C was observed, whereas a modest
decrease in the protein S level was observed."

": In patients with APIC, TDE was well tolerated and produced a modest
response rate, but was not associated with thromboembolic
complications or clinically important changes in several coagulation
factors. Copyright (c) 2005 American Cancer Society."

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

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

"We have recently shown that transdermal estradiol produces an effective tumor
response and negligible cardiovascular toxicity. Here we report the
influence of transdermal estradiol therapy on the coagulation profile
of men with advanced prostate cancer."

"Levels of VIIa and XIIa were unaffected by
transdermal estradiol therapy. Although levels of TAT III were
increased in some patients at 12 months, the increase was markedly
less than that observed historically with equivalent doses of oral
estrogens. Levels of the inhibitory and fibrinolytic factors
including protein C, protein S, APC-R, TPA and PAI-1 remained stable.
Reductions in F1+F2, fibrinogen and D-Dimer levels represented a
normalization from increased levels to the physiological range.
CONCLUSIONS: These results suggest that transdermal estradiol reduces
thrombophilic activation in men with advanced prostate cancer, and
protects against the risk of thrombosis."

Quote from: calico on February 03, 2014, 03:23:10 AMHow about oral as well?

As for oral, a recent study on women who had advanced breast cancer prescribed oral bio-identical estradiol showed that thrombosis only occurred in one women out of 32 after a 6 month treatment.

Also,

Exp Clin Endocrinol Diabetes. 2005 Dec;113(10):586-92.
Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist.


"Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS. There was a significant decline in gonadotropins, total testosterone and calculated free testosterone. In general, the treatment regimen was well accepted. An equal increase in breast size was achieved compared to common hormone therapy. Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged. Significantly increased oestradiol and SHBG serum levels were detectable. In addition, an increase in bone mass density, in the femoral neck and lumbar spine, was recorded. We conclude that cross-sex hormone treatment of male-to-female transsexuals using GnRHa and oestradiol-17beta valerate is effective, and side effects and complication rates can be reduced using the treatment regimen presented here."

Horm Metab Res. 2006 Mar;38(3):183-7.
Effects on the male endocrine system of long-term treatment with gonadotropin-releasing hormone agonists and estrogens in male-to-female transsexuals. (Same transsexuals as the above, with more details)

"We studied hormonal changes resulting from long-term treatment with gonadotropin-releasing hormone agonist and 17beta estradiol valerate in 40 healthy middle-aged male-to-female transsexuals over a period of two years."

"There was a significant reduction in the levels of serum luteinizing hormone and follicle-stimulating hormone to the hypogonadal stage. Mean testosterone levels decreased by 97% to 0.52 and 0.59 nmol/l after 12 months and 24 months, respectively. There was a significant reduction in dehydroepiandrosterone sulfate by 37% after 12 months and 43% after 24 months, and androstendione by 29% after 12 months and 27% after 24 months, respectively. Cortisol levels were reduced by 43% and 50%, respectively. Estrogen levels were significantly increased from 77.51 to 677 after 12 months and 661 pmol/l after 24 months. Sex hormone-binding globulin and corticoid-binding globulin levels were significantly increased after 12 and 24 months. There was a significant decrease in all measured androgen fractions and cortisol during long-term treatment with gonadotropin-releasing hormone agonist and 17beta estradiol valerate." 


Arch Sex Behav. 1998 Oct;27(5):475-92.

A follow-up study for estimating the effectiveness of a cross-gender hormone substitution therapy on transsexual patients.

"This follow-up study was carried out to validate the effectiveness of cross-gender hormone therapy embedded in a multistep treatment concept for transsexual patients. This therapy described in detail by the authors elsewhere and presented briefly below provides cross-gender hormone substitution to obtain an assimilation of secondary sex characteristics to the desired sex as quickly as possible. Personal and social background data of 46 male-to-female (M-to-F) and 42 female-to-male (F-to-M) patients passing through different stages of the treatment concept were included. In the Endocrinological Outpatient Clinic of the Max-Planck-Institute/Munich the effectiveness of cross-gender hormone replacement therapy as well as frequency and distribution of side effects were examined by follow-up examination of endocrinological parameters. Cross-gender hormones were administered either parenterally or orally. Blood samples were collected routinely after 2 to 6 months depending on the duration of hormone substitution and complication rate."

"The incidence of thromboembolic events during the time of cross-gender hormone treatment in our patients is negligible."

"With the cross-gender hormone regimen performed by us it is possible to generate less side effects in the treatment of transsexual patients than described before."

Of those included in treatment (I have full study with details):

14 people on oral estradiol daily, normal to high doses (relative to typical doses for TS women)
2 people on high dose estradiol IM/every 2 weeks
15 people on cyproterone acetate (androcur) daily +  high dose estradiol IM/every 2 weeks
10 people on cyproterone acetate daily + normal to high doses oral estradiol daily

3 were excluded because they finally refused treatment or discontinued and 2 took either ethinyl estradiol or Premarin, one of whom took cyproterone acetate as well.

pmol/L to pg/ml for estradiol is

1 pg/ml = 3.671 pmol/L