Susan's Place Transgender Resources

So, I started HRT in 2014 on a very low dose of estradiol (oral pills) and cyproterone acetate. My testosterone levels went down just fine, but my estrogen levels didn't move much. My estradiol dose was upped, I had an orchiectomy in August 2015, and the cyproterone was discontinued. So, as of now my estradiol dose is 6x where it started, but my estrogen levels won't go up. My estrogen is 100 pmol/L (27.24 pg/mL), but it's my understanding that it needs to be 293.68 - 734.199 pmol/L (80-200 pg/mL). What the hell?

I am being managed by a doctor, so no need to worry that I'll take your advice as medical direction. I'm just looking for ideas or questions that I can throw at my doctor. Has anyone had similar trouble?

It sounds like whatever method of delivery you are using your body isn't absorbing and/or metabolising the estrogen. Maybe a different delivery method perhaps?

That's my hope. My options in Ontario are pretty limited, no implants or injections, and the patches aren't covered as far as know. That would just leave taking my pills sublingually.

Injections should be possible in Canada, there are compounding pharmacies.

https://www.susans.org/forums/index.php/topic,171576.msg1502135.html#msg1502135


*hugs*

As a moderator, I see all kinds of dosage information and am aware of the guidelines that I am being treated with. Some of the starting dosages are extremely low and it would be possible to go up by a factor of 12 and still be safe. You might ask your doctor about the guidelines you are being treated with and learn what it considers a safe dosage. If the doctor isn't treating you with a standard program, it might be time for a little research.

For many years I was on a dosage that was about a quarter the transition dosage. Even at the lower dosage, I still saw additional development of my body though possibly at a slower rate so the levels you are at may still get the job done.

It is really strange, but your estradiol levels are very low, and according to what you said, you are taking a high dose estrogen. Have you tried taking your pills sublingually? And are you taking micronized estradiol pills or estradiol valerate pills? And besides low levels, how do feel about feminization? The same happened to me, On oral pills my estradiol levels were always below 100 pg/ml, and a high dosage!!! On micronized estradiol pills sublingual I felt better and with high estradiol levels, now my only option is estradiol valerate pills sublingual and my feminization became very poor! Doctors say it might do the trick the same! Best wishes!

I wouldn't call my current dosage high, but I don't want to say more out of fear that I might inadvertently break the rules. I'm on micronized estradiol pills, yes. I think I'll try to convince my doctor to bump my dose a bit and switch to sublingual delivery. I just really thought my levels would spike after my orchiectomy, and it's very frustrating that they didn't. I'm not unhappy with my feminization per say. I look very andro without makeup, very feminine with. But breast development is non-existent after 1.5 years, save for a bit of nipple growth. I'll live with whatever I get, but I don't want to give up hope until my levels are where they should be.

After 10 years without, my dosage was started at half a transition dosage. As I have only been on it for a little over a month, I haven't had my levels check so you have something to compare with. The difference in my case is that I had a fair amount of development which diminished while I was off HRT. Now I am back on it, it seems like my body can't change fast enough. A year and a half isn't much if you were started on low dose and then worked up to the current dose. My original HRT what handled that way and after about 4 years, I was still a AA cup size.

Thanks, Dena, and thanks everyone. I'm trying hard not to overreact, but it's so stressful. I'm going full time in 2 months, and I just want everything the way it's supposed to be.

I am tall at 6'2" but it seems that breast really aren't all that important in passing. Face, hair and dress seem to be what people latch onto to because many CIS women don't have large breast either. If it's important to you, breast forms or inserts are available to fill in the gap until you have sufficient development. I chose to go with what little nature provided.

Very interesting Emma, if I were you I would talk with your doctor and see the possibility to up the estradiol dose, but apart from that the sublingual intake could help you, and more if you are on micronized estradiol pills. Many girls in this forum have reported better feminization, including breast growth, with sublingual vs oral. Being On valerate estradiol pills I take them sublingually the same, and I am very thin, but my breasts have developed little but rounded. Try the sublingual way and then tell us about changes ;)!

Quote from: EmmaMcAllister on April 05, 2016, 04:49:09 PM
So, as of now my estradiol dose is 6x where it started, but my estrogen levels won't go up. My estrogen is 100 pmol/L (27.24 pg/mL), but it's my understanding that it needs to be 293.68 - 734.199 pmol/L (80-200 pg/mL). What the hell?

You aren't absorbing estradiol well enough, orally. That's pretty clear. The range for transwomen you state is arbitrarily set by doctors with no scientific basis whatsoever. Some women may do well at these levels while others may do poorly. It depends, individuals vary. Levels in ciswomen range from 20-650 pg/ml during the menstrual cycle and go up to 75,000 pg/ml during pregnancy.

You can ask your doctor to be switched to patches, gels, or injections (estradiol valerate), available through compounding pharmacies throughout Canada (I live in Quebec, get my vials from Toronto for injection). You should see an improvement at least in levels and probably with overall feminization. I did better on injections vs orals. Other forms of HRT may be more costly but worthwhile. Sublingual is indeed another option which might cost you less BUT no point in measuring levels as they will fluctuate widely. Usually, it's best to take dose several times daily to keep levels steadier (avoiding lows).

Quote from: EmmaMcAllister on April 05, 2016, 09:27:45 PM
I just really thought my levels would spike after my orchiectomy

Why would they?

Quotebreast development is non-existent after 1.5 years, save for a bit of nipple growth. I'll live with whatever I get, but I don't want to give up hope until my levels are where they should be.

You shouldn't especially given your very low estradiol levels, similar to post-menopausal women and men. Sublingual might do the trick or switching to another route. Bio-identical progesterone (Prometrium) might also help, once your estrogen dose is settled. :)

Quote from: EmmaMcAllister on April 05, 2016, 10:24:26 PM
I'm going full time in 2 months, and I just want everything the way it's supposed to be.

You had orchiectomy without first going full-time? I didn't know this was allowed and I thought SRS and orchiectomy required the same of individuals.

Quote from: fefi on April 06, 2016, 12:05:36 AM
Many girls in this forum have reported better feminization, including breast growth, with sublingual vs oral.

Not me. Same results.

When I first started HRT, and my memory is a little foggy on this, my doctor told me that there was only one other covered option. I believe that it was cream, and I remember him saying that was less effective. But whatever, if there's a better option that I need to pay for, I'll gladly pay if I can afford it.. One complication, that didn't strike me as a problem initially, is that my doctor is just a general practitioner. He deals with a lot of trans patients that don't want to go through CAMH and can't get into Sherbourne, so I thought it would be fine, but now I'm wondering if he's out of his depth.

I'll pitch sublingual delivery at a higher dose to him as soon as he gets back to me, and I'll ask him about spreading the dose out over the day. If that doesn't amount to significant improvement, I'll try to switch to an entirely different delivery method.

One other thing I'm curious about is the timing of my blood work. My mother is a phlebotomist and she always takes my blood early in the morning before she goes to work. I take my dosage later when I get out of bed, so invariably she ends up taking my blood before my daily dosage and long after my last dosage. Would this suggest that my results are artificially low, or should I still expect much higher levels in the morning before I've taken my dose?

I thought the orchiectomy would help my estrogen levels because it was my understanding that a lower dose would be more effective after the testes were removed. Don't people lower their estrogen dose after SRS? No, I wasn't full-time, but I paid for it myself. I decided at the outset of my transition that the only gatekeeper I wanted was me. So, I found a trans-positive therapist, who directed me to a trans-positive GP that does informed consent, who referred me to a urologist who would perform the orchiectomy for $1000.

Quote from: EmmaMcAllister on April 06, 2016, 12:52:41 PM

I'll pitch sublingual delivery at a higher dose to him as soon as he gets back to me, and I'll ask him about spreading the dose out over the day. If that doesn't amount to significant improvement, I'll try to switch to an entirely different delivery method.

You could ask him for micronized bioidentical estrogen, like estrace or a generic ...
or this:
https://www.susans.org/forums/index.php/topic,70151.msg476820.html#msg476820

Sublingual use is more effective since with swallowing the liver metabolizes a part of it.

Quote
One other thing I'm curious about is the timing of my blood work. My mother is a phlebotomist and she always takes my blood early in the morning before she goes to work. I take my dosage later when I get out of bed, so invariably she ends up taking my blood before my daily dosage and long after my last dosage. Would this suggest that my results are artificially low, or should I still expect much higher levels in the morning before I've taken my dose?

Levels are a bit low. With swallowing it takes a few hours till levels drop. With sublingual intake levels drop a bit faster.

Quote
I thought the orchiectomy would help my estrogen levels because it was my understanding that a lower dose would be more effective after the testes were removed. Don't people lower their estrogen dose after SRS? No, I wasn't full-time, but I paid for it myself. I decided at the outset of my transition that the only gatekeeper I wanted was me. So, I found a trans-positive therapist, who directed me to a trans-positive GP that does informed consent, who referred me to a urologist who would perform the orchiectomy for $1000.

Well your levels of estrogen may stay the same.
But feminization is affected by testostertone and byproducts like DHT . Those are supposed to fall away.
It may take some time though. Sometimes after SRS or an orchi other glands presume low testosterone and try to produce as much as possible. Some people need to take a low dose of anti androgen for a few months afterwards until it levels off.
But afterwards it should be better. And no need to take anti androgens any more.


*hugs*

Yup, I'm on Estrace now.

So, I just got off the phone with my doctor. It was a little disconcerting. He said that my levels are low, but not drastically low. That seems completely bogus to me. We agreed to up my dose slightly, but now I'm at the max he'll be able to prescribe. Again, with his agreement, I'll split the dose into 2 (morning and evening), and I'll take them sublingually. Hopefully this is successful. If it isn't, we'll look at injections, but he doesn't want to go that route because I have very low muscle mass.

FRUSTRATING!

Quote from: EmmaMcAllister on April 06, 2016, 02:11:48 PM
Yup, I'm on Estrace now.

So, I just got off the phone with my doctor. It was a little disconcerting. He said that my levels are low, but not drastically low. That seems completely bogus to me. We agreed to up my dose slightly, but now I'm at the max he'll be able to prescribe. Again, with his agreement, I'll split the dose into 2 (morning and evening), and I'll take them sublingually. Hopefully this is successful. If it isn't, we'll look at injections, but he doesn't want to go that route because I have very low muscle mass.

FRUSTRATING!

Well I'd say try sublingual use ...

With injections and a weekly cycle imo there is not much muscle mass necessary ... you can switch thighs weekly, and if necessary there are other places with muscles ... weekly inections also make for more stable levels.
Many people have good results on injections ... I'd say just talk to them if sublingual does not help ... and maybe it helps, its supposed to be more effective ...
here is a graph showing that it indeed has an influence on levels:
https://www.susans.org/forums/index.php/topic,186946.msg1665088.html#msg1665088


*hugs*

Quote from: EmmaMcAllister on April 06, 2016, 12:52:41 PM
One other thing I'm curious about is the timing of my blood work. My mother is a phlebotomist and she always takes my blood early in the morning before she goes to work. I take my dosage later when I get out of bed, so invariably she ends up taking my blood before my daily dosage and long after my last dosage. Would this suggest that my results are artificially low, or should I still expect much higher levels in the morning before I've taken my dose?

What do you care more about? Your levels or how you are feeling and feminizing? You are focusing way too much on levels, I think. Levels fluctuate...tests don't measure sensitivity.

QuoteI thought the orchiectomy would help my estrogen levels because it was my understanding that a lower dose would be more effective after the testes were removed. Don't people lower their estrogen dose after SRS?

Pre-op, you took cyproterone acetate which lowered T to castrate levels, similar to if testicles were removed. No difference in terms of T. Why would E be lowered? This is an old practice from when estrogen ALONE was used in higher doses to lower T to castrate levels and when the type of estrogen posed greater risks. Times have changed.

Pre or post-op, T is suppressed to the same extent, sometimes even more pre-op because some anti-androgens also BLOCK T (and DHT). 

Quote from: Laura_7 on April 06, 2016, 01:45:19 PM
Sometimes after SRS or an orchi other glands presume low testosterone and try to produce as much as possible. Some people need to take a low dose of anti androgen for a few months afterwards until it levels off.

The idea that "other" glands try to produce as much T as possible to compensate for low T has no scientific basis and is pure myth passed down since many years. The only gland after the op that produces androgens is the adrenal gland and these are usually precursors (DHEA) to T (converted peripherally in tissues).

If you take enough E, LH remains low and even if it were high, it would have no incidence as it does increase adrenal androgen output and testicles are gone.

The only reasons for increased androgenization post-op could be due to:

- stopping HRT before and after HRT so that symptoms would persist for a few weeks due to less E and more T for some time
- Or/and anti-androgens pre-op also blocked androgens so that androgens were actually suppressed to a greater extent pre-op and you experience androgenic symptoms post-op.

Quote from: EmmaMcAllister on April 06, 2016, 02:11:48 PM
He said that my levels are low, but not drastically low. That seems completely bogus to me.

Indeed, when you consider normal range in males is 10-40 pg/ml and you are at the very low range of cisfemales, similar to post-menopausal females.

QuoteI'll split the dose into 2 (morning and evening), and I'll take them sublingually.

Better to take 3-4 times, if doctor agrees, to keep levels more steady but some do well on just twice daily, sublingual also.

QuoteIf it isn't, we'll look at injections, but he doesn't want to go that route because I have very low muscle mass.

So what if you have low muscle mass? I have low muscle mass and I do them in my buttocks where it hurts much less than thighs. Every 5 days and no problem. Been 2 years.

Well, I feel good. I'm really happy with my face, and overall I feel feminine. If I didn't feel as good as I do, I wouldn't be ready to go full time. But knowing that my estrogen is still within the male range bothers me. Because of my low weight and small frame, I'm not hoping for anything miraculous with my chest. But shouldn't I at least be able to hope for something? So, yes, feelings are important, but I have feelings about my levels. :P

I started on sublingual today, so fingers crossed!

Quote from: KayXo on April 06, 2016, 07:53:11 PM

The idea that "other" glands try to produce as much T as possible to compensate for low T has no scientific basis and is pure myth passed down since many years. The only gland after the op that produces androgens is the adrenal gland and these are usually precursors (DHEA) to T (converted peripherally in tissues).

Orchiectomy is often used in the management of metastatic adenocarcinoma of the prostate, ... since it markedly reduces the concentrations of plasma testosterone (to a mean level of 28 ± 16 (SD) ng/100 ml) and temporarily inhibits the growth of the neoplasma. In some orchiectomized patients, however, the values of plasma testosterone and androstenedione do not drop to these levels, but remain higher, around 137 ± 23 ng/100 ml and 213 ± 39 ng/100 ml respectively. In these patients, treatment with dexamethasone significantly decreased the levels of testosterone and androstenedione to 22 ± 20 ng/100 ml (P<0.0005) and 43 ± 11 ng/100 ml (P<0.0005) respectively. It can therefore be assumed that in orchiectomized patients these compounds are produced in the adrenal cortex, which in some cases is stimulated to produce a larger amount of strong androgens such as testosterone and weaker androgens such as androstenedione.


*hugs*

Quote from: Laura_7 on April 07, 2016, 03:48:38 PM
It can therefore be assumed that in orchiectomized patients these compounds are produced in the adrenal cortex, which in some cases is stimulated to produce a larger amount of strong androgens such as testosterone and weaker androgens such as androstenedione.

Indeed, post-op, in some cases, the adrenal cortex produced more androstenedione. But, this is in men who took no estrogen post-op as compared to transsexual women who do. Hence, these findings cannot be applied to us. Perhaps, the presence of estrogen prevents this rise and we have yet (unless you have other studies to provide) to determine with certainty why the adrenal glands, in some, increases its output of androgens. Is this due to high levels of LH/GnRh triggered by insufficient sex hormones? My understanding is that LH and GnRh only affect gonads and not adrenals. 

This study has however raised the possibility of increased adrenal output of androgens post-op as you suggested so you are indeed right and I, wrong, in that respect (thank you for providing this information) BUT we have yet to elucidate the mechanisms behind this and as I earlier stated, this finding cannot be generalized to women who take E post-op as opposed to these men who took none because the circumstances are significantly different. The presence of enough sex hormones (whether E or T) post-op (as should be the case for post-op transwomen) could deter the adrenal cortex from having to produce an increased amount of sex hormones.

The other explanations earlier offered by me can also not be ruled out and may contribute to post-op androgenic symptoms.

In study provided by you, it is stated at the end

"Further studies in a larger number of patients are needed in order to support this finding."

So, in other, later studies...

J Urol. 1977 Dec;118(6):1019-21.

"Selective adrenal vein catheterization was done on intact and castrated men with prostatic carcinoma. Adrenal to peripheral venous testosterone gradients were observed in all patients, indicating adrenal production of this hormone. No compensatory adrenal production of testosterone was noted during a 17-month period after orchiectomy."

Prostate. 1982;3(2):115-21.

"This study, performed on 40 patients having undergone bilateral subcapsular orchiectomy for prostatic carcinoma, shows that this intervention results in testosterone levels in the female range and that during the year following subcapsular orchiectomy there is no evidence for reactivation of Leydig cells or for increased adrenal androgen secretion as evaluated from plasma testosterone, androstenedione, and dehydroepiandrosterone sulphate levels. In patients treated with estrogens we found no evidence for stimulation of adrenal androgen secretion, whereas in neither group of patients with prostatic carcinoma we found evidence for increased androgen levels at the time of recurrence of the carcinoma."

Urol Int. 1990;45(3):160-3.

"Basal serum levels and ACTH-induced increments ('delta-values') of dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and testosterone and serum albumin levels were studied in patients with prostatic cancer before treatment and after orchidectomy or during estrogen treatment (intramuscular polyestradiol phosphate during the first 3 months, followed by another 3 months with additional oral ethinyl estradiol). Orchidectomy as well as single drug intramuscular or oral + intramuscular estrogens exerted a similar suppressive effect on basal levels of A-4 and 17-OHP."

Prostate. 1989;14(2):177-82.

"Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels."

Urol Res. 1989;17(2):95-8.

"Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone (17OHP), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS) and cortisol were measured before and after 6 months of treatment in prostatic cancer patients treated by orchidectomy (ORX) or with oral + parenteral estrogens (OE), single parenteral estrogens (...), estramustine phosphate (ECYT) or LHRH agonist without (LHRH) or with (LHRH-F) flutamide. Castration values of T and 170HP were reached in all types of treatment (PE at the higher dose).

Int J Androl. 1987 Aug;10(4):581-7.

"Orchidectomy caused a pronounced decrease in 17-OHP levels and minor but significant decreases in the levels of A-4 and DHAS."

"The results further invalidate the hypothesis that there is a 'compensatory' increase in adrenal androgen output following orchidectomy."

In full study...

"Although increased urinary excretion of androgens has been reported after
orchidectomy in several earlier studies (Parker et al., 1984), unchanged or slightly
decreased blood levels of DHA, DHAS and A-4 were reported in more recent
investigations (Luukkarinen et al., 1977; Vermeulen et al., 1982a; Parker ef al.,
1984; Belanger ef al., 1984; Belanger, Brochu & Cliche, 1986). With respect to
oestrogen treatment, modest doses of polyoestradiol phosphate or oestradiol undecylate
administered intramuscularly are reported to cause a slight decrease in A-4
and a slightly decreased, or unchanged, level of DHAS, while the levels of DHA
remained unchanged (Jonsson et al., 1975; Luukkarinen et al., 1977; Leinonen ef
al., 1981; Vermeulen et al., 1982a; Schurmeyer et al., 1986). A dose-dependent
decrease in DHAS levels has also been observed in postmenopausal women during
oral oestrogen replacement therapy (Helgason et al., 1981)."

For what it's worth, 8 months out from my orchiectomy, my free T is 3 pmol/L, or 0.003 nmol/L. I'm not too worried about increased adrenal production. 

And more...

J Clin Endocrinol Metab. 1984 Sep;59(3):547-50.

"Prostatic carcinoma is androgen dependent and, therefore, treated by orchiectomy. However, adrenal androgen secretion remains intact after orchiectomy, and several investigators even reported an increase in serum adrenal androgen concentrations after orchiectomy. Such an increase in androgen secretion theoretically could promote tumor recurrence. To investigate this question, we obtained multiple blood samples from 10 men before, within 1 week after, and up to 6 months after orchiectomy for prostatic carcinoma. Serum testosterone concentrations became unmeasurable (less than 40 ng/dl) after orchiectomy. Three of the 10 patients had transient increases of at least 50% in both serum dehydroepiandrosterone (DHA) and cortisol after orchiectomy, presumably due to surgical stress, but mean serum DHA and DHA sulfate (DHAS) did not increase in the group as a whole. Subsequently, serum DHA and DHAS concentrations were similar to preoperative values in all patients. Therefore, we find no evidence to support the hypothesis that adrenal androgen concentrations increase after orchiectomy."

Perhaps, some transwomen who are especially stressed due to the surgery or change in their lives may be more prone to produce higher levels of adrenal androgens so that adrenal output is not increased in response to low T (or low sex hormones) as Laura suggested but in response to stress, which follows a life changing surgery, which may be more significant in some vs others. This makes much more sense, in my opinion and would account for why some men experienced increased adrenal output of androgens, post-op while others didn't.

To conclude:

Only 2 out of 8 studies showed orchiectomy to result in increased levels of adrenal androgen output. In those two studies, 37% of men and 30% of men had increased output, less than 50% (about 1 in 3 men) AND in one study, the increase was transient, perhaps correlated with stress (higher cortisol) and not low T.

On the other hand, these studies were not in transsexual women who take E post-op. Studies have shown E to actually sometimes reduce adrenal androgen output in men and in women which would suggest that taking E post-op would help counter the rise in adrenal androgen output, if it occurs, perhaps due to stress.

There could be other explanations as well for why androgenic symptoms increase post-op in some transwomen.

So, an update. After a little more than a month taking my estradiol buccally (which I find easier than sublingual) my estradiol levels have gone from 100 pmol/L (27.24 pg/mL) to 2763 pmol/L (752.65 pg/mL). So now it seems that I have the OPPOSITE problem. I suspect my doctor will want to cut my dosage, but honestly, I've been progressing amazingly in this past month. So unless this high of a level is incredibly dangerous, I'd rather not go down.

If you took your dosage the same day you were tested, those number could be misleading. It's possible that within a few hours, your levels could drop to more normal ranges as your blood passes through your liver. Remember that you have only eliminated the first pass problem but sooner or latter, all the estradiol will pass through the liver and be processed. The time between the last dose and the blood test is very important in determining your true levels.

I took my night dose at approximately 11pm on Thursday, and had my blood drawn at approximately 10am on Friday before I took my day dose. So, shouldn't it have dropped sufficiently by then?

I was told not to take it a day before being tested. I hear all sorts of numbers for half lives, but I suspect another 12 hours would have quartered your levels and they might have dropped even more. The information I have can't directly be applied to the way you are taking your hormones so my answer is somewhat of a guess as to what your true levels would be. Needless to say, if your levels are that high after 24 hours, possibly a level reduction should be considered but after 11 hours it's hard to say.

Quote from: EmmaMcAllister on May 21, 2016, 12:24:45 PM
So, an update. After a little more than a month taking my estradiol buccally (which I find easier than sublingual) my estradiol levels have gone from 100 pmol/L (27.24 pg/mL) to 2763 pmol/L (752.65 pg/mL). So now it seems that I have the OPPOSITE problem. I suspect my doctor will want to cut my dosage, but honestly, I've been progressing amazingly in this past month. So unless this high of a level is incredibly dangerous, I'd rather not go down.

Pregnant women have levels up to 75,000 pg/ml, clotting incidence is less than 0.2%. In men with prostate cancer, levels up to 700 pg/ml have not been found to cause health problems, namely cardiovascular and clotting. These men ranged in age from 49-91 yrs old. My estradiol levels are 1,000-4,000 pg/ml, I'm healthy, clotting factors are normal so is C-reactive protein. I'm supervised by three doctors.

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

"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."

Br J Obstet Gynaecol. 1990 Oct;97(10):917-21.

"There is some anxiety about the possible harmful sequelae of supraphysiological estradiol levels but no data are currently available to show any deleterious effects of these levels on coagulation factors, blood pressure, glucose tolerance or the occurrences of endometrial or breast cancer (Hammond et al. 1974; Thom et id. 1978; Studd B Thom 1981; Armstrong 1988)."

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."

No sense in measuring levels as there is neither an ideal level for feminization, is not a good gauge of health risks and fluctuates in 24 hours.

Quote from: Dena on May 21, 2016, 12:49:33 PM
If you took your dosage the same day you were tested, those number could be misleading. It's possible that within a few hours, your levels could drop to more normal ranges as your blood passes through your liver. Remember that you have only eliminated the first pass problem but sooner or latter, all the estradiol will pass through the liver and be processed. The time between the last dose and the blood test is very important in determining your true levels.

Much less estradiol will pass through the liver and the small amount that eventually circulates through the portal vein is so small as to negligibly affect clotting or liver. Estradiol is easily metabolized and eliminated by the liver so there is no second and third pass like non bio-identical estrogens.

There is no such as true or normal level as levels fluctuate so much and normal in women can be anywhere from 20-75,000 pg/ml.

I really wish there was some universal consensus on these matters. I expect my doctor will try to bring my levels down to a max of 400 pg/mL, but I'm just not sure what the best thing to do would be. My breasts are just now starting to bud significantly, so I don't want to take a step backwards.

Quote from: EmmaMcAllister on May 23, 2016, 03:54:42 PM
I really wish there was some universal consensus on these matters.

There should be but doctors are simply misinformed or uninformed. Doctors need to be better educated. And take the time to read the studies that are out there.

Quote from: EmmaMcAllister on April 06, 2016, 12:52:41 PM

One other thing I'm curious about is the timing of my blood work. My mother is a phlebotomist and she always takes my blood early in the morning before she goes to work. I take my dosage later when I get out of bed, so invariably she ends up taking my blood before my daily dosage and long after my last dosage. Would this suggest that my results are artificially low, or should I still expect much higher levels in the morning before I've taken my dose?

Hi Emma, I had the same issue with a low E reading after being told not to take my meds: Estradiol  E2 74.2 pg/ml after being nearly 300 in December (https://www.susans.org/forums/index.php?topic=209373.new;topicseen#new ). So I laid off E for over 12 hours before the result and, guess what, it came back low. So I'm pretty certain that's the reason with yourself.

I'm currently in my first week of IM estradiol valerate. I can't in all honesty say that I'm enjoying it very much and will almost certainly return to sublingual. However, under the guidance of the clinic, I'm going to mix up the types of oestrogen a little each day with 2 x estradiol valerate and 1 x straight oestrogen. I always take them sublingually. I'm also going to be more strict about taking those every 8 hours. I don't know if this will help but I would definitely recommend the sublingual route.

Sorry, I've just read your updates on this page. Wow!!!! I'm so pleased for you. Go girl :)

Interesting about your buccal delivery. I'm a big fan of sublingual / buccal.

Yup, the difference is pretty staggering. I really don't know why anyone would bother with oral administration. I know my individual experience can't be universalized, but oral seems so ineffectual. I'm still wondering if injections might be the best way to go though, because the peaks and valleys might better mimic the natal female cycle.

I'm at the end of day 5 of my first week of injection and it's likely to be my last. In fact, scrub that, it is my last. I haven't found the experience at all pleasant. I felt pretty rough for the first three days: hot flashes, rushes, then alternating periods of virtual narcolepsy. I've felt completely out of it at times. It really was horrible.

So I'm returning to my tried and trusted sublingual, just nudging the dosage up a touch and varying the pills between estradiol valerate straight oestrogen. I can't say more on that because although I won't mention dosage the frequency might break the rules.

What I'm going to focus on now more is my anti androgen, starting bicalutamide to go alongside the finasteride.

I'm writing all the above because I guess everyone really is different and you need to follow what's right for you Emma imho. I'm thrilled for you at the way your estrogen level has shot up. Continue to work with your body: it's yours and no-one else's.

Quote from: EmmaMcAllister on May 27, 2016, 09:20:07 AM
I'm still wondering if injections might be the best way to go though, because the peaks and valleys might better mimic the natal female cycle.

I think the female cycle isn't natural and is only a recent phenomena due to modernization. Cycles lead to constant proliferation and apoptosis which can increase the likelihood of cancerous cells. They also lead to mood swings. I personally see no reason to mimic this.

Traditionally, women would spend most their lives being pregnant and nursing with hormone levels being much more steady.

Quote from: Richenda on May 27, 2016, 09:51:00 AM
I'm at the end of day 5 of my first week of injection and it's likely to be my last. In fact, scrub that, it is my last. I haven't found the experience at all pleasant. I felt pretty rough for the first three days: hot flashes, rushes, then alternating periods of virtual narcolepsy. I've felt completely out of it at times. It really was horrible.

Your dose is likely too low. Estrogen load is less now.

QuoteSo I'm returning to my tried and trusted sublingual, just nudging the dosage up a touch and varying the pills between estradiol valerate straight oestrogen.

No difference between estradiol valerate and estradiol.

Maturitas. 1982 Dec;4(4):315-24

"After oral or parenteral administration, oestradiol valerate, the synthesis compound contained in various commercially available preparations, is completely converted into the natural substances 17 beta-oestradiol and valeric acid. The 17 beta-oestradiol produced on cleavage of the ester behaves in the organism like the endogenous steroid hormone. Oestradiol valerate and 17 beta-oestradiol are virtually dose-equivalent. No differences in the spectrum of action of the oestrogen and its ester have been found either in animal experiments or man. The pharmacokinetic behaviour and the biotransformation of the 17 beta-oestradiol originating from oestradiol valerate are no different from those of natural 17 beta-oestradiol."

I personally found no difference between taking E sublingually vs orally. Same results and orally, was more convenient with less ups and downs.

So, my doctor cut my dose in half, as I expected he would. Beyond my estradiol levels, he was concerned about my hemoglobin. So, back to once a day, retest in a few weeks.

Hi Emma,

Am I allowed to ask what the haemoglobin result was? I had a low result too and have been taking iron supplements and watching my diet. Don't know yet if that will help.

128 g/L, down from 135 g/L the month before.

Ah okay. Mine was 140 g/L at last checkup. I was low on protein, sodium and chloride so have changed my diet and added protein which I think raises haemoglobin?

I'm starting on bicalutamide today but that's another story.

Quote from: KayXo on May 30, 2016, 02:08:06 PM

No difference between estradiol valerate and estradiol.


I personally found no difference between taking E sublingually vs orally. Same results and orally, was more convenient with less ups and downs.

Neither statement is factually correct.

Oral vs sublingual has different effects if this admittedly small double blind study is correct: http://www.sciencedirect.com/science/article/pii/S0029784496005133

"Results:

Sublingual administration resulted in rapid absorption with significantly higher E2 levels than did comparable oral dosing. Estrone levels did not vary with route of administration but correlated with the dosage administered. Estrone sulfate levels correlated with the dosage administratered and also tended to be higher with sublingual administration. Sublingual administration resulted in a significantly lower E1 to E2 ratio during the 24 hours than did oral administration.

Conclusion:

Sublingual administration of micronized 17β-estradiol results in a rapid, burst-like absorption into the systemic circulation, yielding high E2 levels that fall rapidly over the first 6 hours."

The valerate version of estradiol is different. It binds to a carbonyl to create an ester of estradiol. As a result it creates a prodrug which is much more benign and not easily absorbed or reactive. So this radically slows down absorption, which leaves it in the system longer https://en.wikipedia.org/wiki/Estradiol_valerate

There is something to be said for mixing the two forms if one is using oral or sublingual route of administration (preferable).

I can actually feel a twitchy surge of energy from buccal administration. I never felt that from oral administration.

Quote from: EmmaMcAllister on May 31, 2016, 12:08:35 PM
So, my doctor cut my dose in half, as I expected he would. Beyond my estradiol levels, he was concerned about my hemoglobin. So, back to once a day, retest in a few weeks.

Hemoglobin levels are lower in females and may drop a little when on estrogen. Best to compare your levels to female levels.

Quote from: Richenda on June 01, 2016, 11:21:42 PM
Neither statement is factually correct.

Oral vs sublingual has different effects if this admittedly small double blind study is correct: http://www.sciencedirect.com/science/article/pii/S0029784496005133

"Results:

Sublingual administration resulted in rapid absorption with significantly higher E2 levels than did comparable oral dosing. Estrone levels did not vary with route of administration but correlated with the dosage administered. Estrone sulfate levels correlated with the dosage administratered and also tended to be higher with sublingual administration. Sublingual administration resulted in a significantly lower E1 to E2 ratio during the 24 hours than did oral administration.

Conclusion:

Sublingual administration of micronized 17β-estradiol results in a rapid, burst-like absorption into the systemic circulation, yielding high E2 levels that fall rapidly over the first 6 hours."

I don't dispute the fact that E taken sublingually yields significantly higher levels, I've read this study and many more like these. But, in my case and in the case of others (but not all transwomen), physically and psychologically speaking (regardless of levels in the blood at any point in time), results were similar, whether oral or sublingual. That's all I'm saying. So, for me, I just took it orally and saw no point in taking it sublingually. Bio-identical, I consider, based on several studies, to be quite safe, even when taken orally so from that standpoint as well, saw no significant advantage taking it sublingually.

QuoteThe valerate version of estradiol is different. It binds to a carbonyl to create an ester of estradiol. As a result it creates a prodrug which is much more benign and not easily absorbed or reactive. So this radically slows down absorption, which leaves it in the system longer https://en.wikipedia.org/wiki/Estradiol_valerate

They state "especially when given in an oil solution via intramuscular injection". Also,

Maturitas. 1982 Dec;4(4):315-24.

"After oral or parenteral administration, oestradiol valerate, the synthesis compound contained in various commercially available preparations, is completely converted into the natural substances 17 beta-oestradiol and valeric acid. The 17 beta-oestradiol produced on cleavage of the ester behaves in the organism like the endogenous steroid hormone. Oestradiol valerate and 17 beta-oestradiol are virtually dose-equivalent. No differences in the spectrum of action of the oestrogen and its ester have been found either in animal experiments or man. The pharmacokinetic behaviour and the biotransformation of the 17 beta-oestradiol originating from oestradiol valerate are no different from those of natural 17 beta-oestradiol."

Arzneimittelforschung. 1998 Sep;48(9):941-7.

"A randomized, single-dose cross-over study in 32 postmenopausal women was performed to demonstrate bioequivalence of two estradiol valerate containing formulations"

"The terminal elimination half-life of estradiol was calculated at 16.9 +/- 6.0 h (Test) and 15.0 +/- 4.8 h (Reference), that of free estrone at 16.3 h (Test) and 13.5 h (Reference)"

Vs.

https://en.wikipedia.org/wiki/Estradiol

biological half-life is stated to be 13-17 hours.

In the end, the difference when taken orally between E2 and EV, if any, is minimal. A study states lower estrone levels with EV and another slightly lower estradiol levels.