Flummoxed by low estrogen levels

[EmmaMcAllister]

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?

[Ms Grace]

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?

[EmmaMcAllister]

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.

[Laura_7]

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

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


*hugs*

[Dena]

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.

[fefi]

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!

[EmmaMcAllister]

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.

[Dena]

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.

[EmmaMcAllister]

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.

[Dena]

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.

[fefi]

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 !

[KayXo]

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).

I just really thought my levels would spike after my orchiectomy

Why would they?

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.

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.

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.

Many girls in this forum have reported better feminization, including breast growth, with sublingual vs oral.

Not me. Same results.

[EmmaMcAllister]

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.

[Laura_7]

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.

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.

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*

[EmmaMcAllister]

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!

[Laura_7]

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*

[KayXo]

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.

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?

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). 

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.

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.

I'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.

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.

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.

[EmmaMcAllister]

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.

I started on sublingual today, so fingers crossed!

[Laura_7]

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*

[KayXo]

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.