Ok, keeping dosage level specifics out, this is purely a question about fluctuating serum levels and what is a normal daily cycle. Please do not ask for dose specifics.

So for the past year I have been on Injectable Estradiol Valerate. My E levels were consistently high, like around 400pg/mL. prolactin level eventually rose to 29ng/mL, so we switched to sublingual at half the dose concentration equivalent. Spiro remained the same (recommended dose). After one month my E and Prolactin levels had dropped, T increased just slightly.

We then doubled up on my sublingual dose (equivalent dose my injection was). 2 1/2 months of being on sublingual my E was 27pg/mL, T 65ng/dL, and Prolactin bottomed out to 7ng/mL. My lab was 8 hours after taking a morning dose (1/4 my daily dose).

Question. Should estradiol levels drop so dangerously low between dosage on sublingual? On the shot it was consistently high every lab test. I'm debating about changing Dr's. and going back on the shot. Since I have noticed a slight drop in weight and more hair shedding than usual.

I would talk to your existing doctor first. Your T looks high but was the test total or free T. Reason being pills provide a higher SHGB so all the T may not be free. You may ask your doctor if sublingual pill taking of E is recommended. Also, pills peak fast and decline fast. When I was on pills I use to split my E pills to AM and PM.  I like IM much better than pills and my E is high and my T is <20 ng/dl.

It was total T.

Quote

Question. Should estradiol levels drop so dangerously low between dosage on sublingual? On the shot it was consistently high every lab test. I'm debating about changing Dr's. and going back on the shot. Since I have noticed a slight drop in weight and more hair shedding than usual.

Estradiol Valerate Injection is slowly released and continually maintains relative stable blood levels. Sublingual Estradiol is rapidly adsorbed and produces a peak blood level within minutes. Without any additional release of Estradiol, the bodies elimination processes start to lower the Estradiol blood levels immediately and are almost completely gone in about 12 hours.

This is not dangerous in any way, as natal women have hormone fluctuations daily and monthly. The big advantage of sublingual Estradiol is that it is absorbed directly into the blood system, avoiding the first pass through the liver, as what happens if absorbed through the stomach lining. This means that for each mg of Estradiol, you will get much higher blood levels via sublingual route. Injection with Estradiol Valerate gives a lower peak blood level, but a more consistent blood level, lasting a week or two.

Why didn't you just stay on shots? You have essentially made things worse by switching to sublingual, where levels fluctuate much more, from very high to very low in a matter of just a few hours and where levels drop more significantly.
I have much better results on injections than on high dose sublingual. I would NEVER switch back.

If your doctor is concerned about high levels on injectables, why aren't they concerned the same on sublingual where levels peak quite significantly, even if for a 1-2 hours? They also should be made aware that pregnant women have levels up to 75,000 pg/ml and yet their risk of DVT remains under 0.02%, that breast cancer risk is lower in women who've had pregnancies and increases when estradiol levels drop after menopause, that in men with prostate cancer (49 yrs old - 91 yrs old) levels up to 700 pg/ml were shown NOT to be associated with an increase in cardiovascular and thrombogenic complications and actually shown to protect against the occurrence of DVT.

I have levels ranging from 1,000-4,000. All blood tests came back normal, liver, clotting, lipids, insulin, glucose, etc. Prolactin was expectedly high but no concerns. It was 87-130 ng/ml. Levels can go as high as 210 in pregnant women and remain quite high (over 50-200) during breastfeeding which can lasts years. Studies have never shown incidence of prolactinoma with bio-identical estradiol or due to pregnancy/breastfeeding.

here is a graph showing how intake influences levels:
https://www.susans.org/forums/index.php/topic,186946.msg1665088.html#msg1665088

if used sublingual there are spikes for a few hours...
if simply swallowed not... but sublingual is supposed to be less straining on the liver... and less causing clotting factors...

one way to avoid spikes a bit can be spreading the daily dose in a few small doses instead of two big ones...

Quote from: Dani on January 31, 2016, 07:26:20 AM
This is not dangerous in any way, as natal women have hormone fluctuations daily and monthly.

I would disagree . Fluctuations of this kind are a complete menstrual cycle compressed into a few hours.
That means going from a normal state to a pms like state a few times a day. Imo it can have a great influence on mood in some people. I would go so far as that it might even make for a less stable personality in some cases.
So spreading the daily dose over a few small doses , say four times a day instad of two, might be very helpful.

I would agree with Kay that you might stay with injections.
Many people are happy with injections or implants and report good results.
There are subcutaneous injections with small needles which might be less painful.


hugs

Believe me, I wanted to stay on injections, however, my new Dr. refuses to put me back on the shot.

Quote from: Leeloo_Dallas on January 31, 2016, 04:25:03 PM
Believe me, I wanted to stay on injections, however, my new Dr. refuses to put me back on the shot.

Well maybe its time for a new doctor ? 

You might look up lgbt resources or transgender endos in your vicinity ...
plannedparenthood could also be a possibility ...


hugs

Quote from: Leeloo_Dallas on January 31, 2016, 04:25:03 PM
Believe me, I wanted to stay on injections, however, my new Dr. refuses to put me back on the shot.

Why? If they judge risks to be high, explain what I wrote earlier. I can send you evidence, studies privately, if you wish.

Quote from: Laura_7 on January 31, 2016, 05:30:48 PM
Well maybe its time for a new doctor ? 

You might look up lgbt resources or transgender endos in your vicinity ...
plannedparenthood could also be a possibility ...


hugs

Already in the works, I have an old doctor that was great. I switched to VA care because, well.. it was free. I feel I had better communication with my old dr. and it's worth paying for.

Quote from: KayXo on January 31, 2016, 09:37:16 PM
Why? If they judge risks to be high, explain what I wrote earlier. I can send you evidence, studies privately, if you wish.

I talked with my existing dr. again briefly about the levels I experienced on sublingual. She stated that the levels are not important it's how you feel and if they are producing results. Also that it wasn't about how high they are, but how safe they are. She would not increase my dosage or return to intramuscular because she feels its not safe to go that high. (On a fairly standard dose now).  I feel conflicted, she has years of experience in this area, however, her approach is vastly different than my previous endo... really upset at this point.

Quote from: Leeloo_Dallas on February 02, 2016, 10:06:52 AM
She would not increase my dosage or return to intramuscular because she feels its not safe to go that high. (On a fairly standard dose now).

What are the risks?

1) Cardiovascular and clotting risks

. Studies in men with prostate cancer (ages 49-91) have shown that levels up to 700 pg/ml were safe. There were no cardiovascular complications or incidences of thrombosis. In fact, researchers stated high levels could be PROTECTIVE. They were treated with high dose injectable or transdermal (patches) estradiol. I can provide you those studies. 

. Pregnant women have levels that go as high as 75,000 pg/ml and yet the risk of having a DVT or pulmonary embolism is less than 0.02 % with pulmonary embolism being extremely rare during pregnancy. I can provide you the evidence as well.

. Ciswomen are also reported to be much less affected than men by cardiovascular complications despite pregnancy levels of estradiol and levels of up to 650 pg/ml every menstrual cycle. Their risks increase post-menopause when estrogen levels DROP. Studies have strongly suggested a role for estrogen. I can provide these studies as well.

. Am J Obstet Gynecol. 1993 Dec;169(6):1549-53.

"As serum estradiol levels increased throughout each phase (maximum mean estradiol 739.8 pg/ml)"

"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."

. Arch Sex Behav. 1998 Oct;27(5):475-92. In this study, transsexual women were given high dose intramuscular E. Despite 17 people being on this regimen, there was not one incidence of thrombosis.

"None of our patients developed deep vein thrombosis or embolism during cross-gender hormone therapy performed in our clinic."

2) Breast cancer risk

. In transsexual women, breast cancer incidence is very low, equal to that of men not on HRT. Only 10 cases reported since 1968 despite decades of very aggressive, high doses of oral estrogens and non-oral estrogens (intramuscular). Only one case reported in Holland among Gooren's patients in decades of treatment. Studies to support this.

. In men with prostate cancer treated with high dose estrogen over the years, since the 1960's, breast cancer is extremely rare. Supporting evidence.

. High dose estrogen has actually been used to treat ciswomen afflicted with breast cancer.

. Randomized controlled trials (the strongest form of study) showed estrogen to be either protective of breast cancer incidence or have no effect, even in women who had had breast cancer. I can provide studies.

. The more childbirths a woman (hence, the more pregnancies), the lower the risk of breast cancer. On the other hand, celibate nuns are historically known to have a higher incidence of breast cancer risk.

. Breast cancer risk is highest in women over the age of 40 and especially 50, when estrogen levels drop.

3) Uterine cancer risk

. YOU HAVE NO UTERUS

4) Prolactinoma

. Ciswomen have very high levels of prolactin, up to 210 ng/ml, during pregnancy and continue to have high levels during breastfeeding which can sometimes last a few years. As far as I know, prolactinoma is not more prevalent in women because of this and this has never been called into question by doctors asking mothers to stop breastfeeding their children or not become pregnant again due to risk of prolactinoma.

. In my extensive search through incidences of prolactinoma in transsexual women, the only incidences reported were found to be in those women who took non bio-identical forms of estrogen orally (ethinyl estradiol, DES or conjugated equine estrogens) with or without cyproterone acetate, known to abnormally elevate prolactin levels. Incidences in women taking bio-identical estradiol without the above mentioned agents taken simultaneously have NEVER been reported to date.


On the flipside, ask her to provide studies (not statements made by an association) to support her assertions.

By the way, I'm on a high dose of intramuscular E. Supervised by three doctors who approve, one of whom is an author of a book on female hormones, another a trans-specialist endocrinologist from the University of Cambridge. My blood tests results show no change in clotting factor, or liver enzymes, or lipids, insulin, glucose, c-reactive protein. Nothing is out of range given my high levels of E2, which are in the range of 1,000-4,000 pg/ml.

Quote from: Leeloo_Dallas on February 02, 2016, 10:06:52 AM
I talked with my existing dr. again briefly about the levels I experienced on sublingual. She stated that the levels are not important it's how you feel and if they are producing results. Also that it wasn't about how high they are, but how safe they are. She would not increase my dosage or return to intramuscular because she feels its not safe to go that high. (On a fairly standard dose now).  I feel conflicted, she has years of experience in this area, however, her approach is vastly different than my previous endo... really upset at this point.

Do not forget that they are human.
Humans tend to interpret information in a way in alignment with their emotions and beliefs.
If she believes it is not safe she will look for data supporting that view.
But it is not necessarily the truth.

Being objective and without emotional attachment might help here.

Lets gather a few facts.
As Kay said, higher doses applied internally seem to have very few side effects.
You might tell her that. Or directly switch to another doctor, its your choice.

Most studies are based on oral intake of non bioidentical estrogen.
Even people from medical fields tend to overlook this . Bioidentical can make a big difference.
One example is progesterone. The bioidentical forms have different effects.
Yet most people are simply talking about progesterone, mixing in non bioidentcal forms though they are different.

It is well known that during pregnancy breasts swell and increase. Part of this increase is permanent.
This increase is due to a higher level of both bioidentical naturally produced estrogen and progesterone.
Its a well known effect.

Also well known is an effect where with higher doses of estrogen production of testosterone is shut down.
This is only considered safe with internal applications. Quite a few endos use this effect for raising the estrogen levels well into the female range and doing without anti androgens.
So its well possible to take advantage of higher levels of estrogen.

You might talk this through with your doc or look for another one more open to such concepts.
Its entirely up to you.


hugs

I have a consult Monday with my original dr. I most likely will return to his care and pay for HRT out of pocket again. Just not comfortable with this current Dr.

Thanks!

Hopefully, this doctor is better. Good luck.