Do you take your estrogen once or twice a day?

[Briezy]

When my doses for estradiol and spiro were doubled after the first month I essentially went from taking one pill of each to taking two pills of each (which I think is ok to say since I'm not giving doses). When I was on just one pill of each I didn't bother to split them since I figured it was just a starting dose and it would be raised on my next visit so I just took them in the morning.

When the doctor did double each he did tell me to take the spiro twice a day but it didn't matter about the estradiol. Now I have read posts from women who in my situation would cut each of the estradiol in half and take it four times a day to try and keep levels steady. I am wondering what everyone's experience is and what scientific evidence, if any, that would support one, the other, or that it doesn't matter.

Thanks! 

[April_TO]

Hello,

I take mine every 8 hours and it seems to be working. My blood work has been coming back with Estradiol levels close to a pregnant woman and T levels on the female range. I have been doing this for almost 2 years.

I think the reason we split our meds is to get an even level of E than just taking it once a day.

Hope this helps!

[Deborah]

My Dr. prescribed it for twice a day.


Sapere Aude

[Starfire]

I take my estradiol in three doses every day, 8 hours apart.  It's working fine for me and theoretically it should provide more even blood levels but who knows if that really makes any significant difference or not.

[KayXo]

When the doctor did double each he did tell me to take the spiro twice a day but it didn't matter about the estradiol.

Since it doesn't matter to doctor, I would rather take estradiol twice daily as half-life is around 13-17 hours so as to make levels a little more steady.

Now I have read posts from women who in my situation would cut each of the estradiol in half and take it four times a day to try and keep levels steady.

This could be the case in those who take it SUBLINGUALLY because levels increase and drop FAST. Orally, this is not the case and personally, I saw no difference in either route of administration in terms of feminization, breast growth, well-being.

I take mine every 8 hours and it seems to be working. My blood work has been coming back with Estradiol levels close to a pregnant woman

Close to a pregnant woman on oral estradiol?!  Are you taking it sublingually and measuring levels shortly after? What are your levels? Yours will be in pmol/L. And are these estrogen (estradiol + estrone) or estradiol levels?

[Briezy]

This could be the case in those who take it SUBLINGUALLY because levels increase and drop FAST. Orally, this is not the case and personally, I saw no difference in either route of administration in terms of feminization, breast growth, well-being.

Ha, well this was my other question but I didn't want to muddle the thread too much. The prescription bottle just says take 2 pills daily. I started with just swallowing them but then I started reading about how everyone is saying sublingually is better. I have not asked my doctor yet, but the funny thing is The Fenway where I go has printed guidelines for their doctors in the treatment of transgender patients and in that guideline it states to prescribe the medication sublingually which I thought was pretty interesting since it's the guidelines for a large group of doctors who treat transgender patients.

[Laura_7]

Here is a graph showing how levels rise, sublingually and oral:

https://www.susans.org/forums/index.php/topic,186946.msg1665088.html#msg1665088


With sublingual intake the liver is bypassed, which lessens strain on the liver, and also blood clotting. Its also more effective since the liver breaks down part of it.
If there is estrogen in the digestive tract the liver presumes a leak and raises clotting factors.

With sublingual intake levels rise fast, and drop after a few hours. So spreading the daily dose in a few small doses might be a good idea. There are small dose pills for example, or there are pills which can be seperated in half...

You might talk about all of this with your doc.


*hugs*

[KayXo]

With sublingual intake the liver is bypassed, which lessens strain on the liver

Can you point to studies where bio-identical estradiol strains the liver?

Gynecol Endocrinol. 1993 Jun;7(2):111-4.

"Serum concentrations of sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG), ceruloplasmin, lipoprotein A and liver enzymes were measured in 30 postmenopausal women treated with (...) micronized 17 beta-estradiol daily and micronized progesterone orally (...), as progestogen supplementation. The treatment lasted for 4 months. The serum levels of SHBG and CBG increased during treatment and a weak association between progesterone dosage and CBG was observed. Levels of lipoprotein A and liver enzymes did not change. It is concluded that micronized natural progesterone is an attractive means of progesterone supplementation in postmenopausal hormone replacement therapy without any liver-related side-effects."

Exp Clin Endocrinol Diabetes. 2005 Dec;113(10):586-92.

" 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."

"Liver enzymes, lipids, and prolactin levels were unchanged."

Hepatol Res. 2007 Apr;37(4):239-47.
Protection of estrogens against the progression of chronic liver disease.

"Hepatic steatosis was reported to become evident in an aromatase-deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures."

and also blood clotting.

Journal of Clinical & Translational Endocrinology 2 (2015) 55-60

"Other compelling data suggest that the incidence of venous thromboembolism (VTE) among transgender women appears associated with the presence of a hypercoaguable risk factor, including the use of an especially thrombogenic estrogen (ethinyl estradiol) which is no longer used [3]. Gooren et al. (2008), reported no increase in VTE among 2236 male-to-female (MTF) transgender individuals on HT from 1975 to 2006 compared with controls, with the exception of those who used ethinyl estradiol, for which there was a 6-8% incidence [4]."

Menopause. 2006 Jul-Aug;13(4):643-50.

"Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis."

Fertil Steril. 1997 Sep;68(3):449-53.

« Compared with placebo, oral E2 replacement therapy resulted in a significant decrease in fibrinogen and apo B and a significant increase in plasminogen."

Exp Clin Endocrinol Diabetes. 2005 Dec;113(10):586-92.

"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."

"Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation."

Archives of Sexual Behavior, Vol. 27, No. 5, 1998

"The incidence of thromboembolic events during cross-
gender hormone treatment in our patients was zero."

Despite moderate to high doses of oral bio-identical estradiol.

J Clin Endocrinol Metab. 2003 Dec;88(12):5723-9.
Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people.

"In conclusion, we have shown that treatment of MtF transsexuals with sex steroid hormones (CPA combined with E2 or EE) affects the hemostatic balance with a very pronounced difference in the effects of oral EE compared with the effects of both td E2 or oral E2. Oral EE induces a clinically relevant prothrombotic state."

Aust N Z J Obstet Gynaecol. 1978 Aug;18(3):198-201.

"The effect of oestradiol valerate on levels of blood cholesterol, triglycerides, free oestradiol and coagulation factors, as well as on urinary oestrogens and free cortisol was measured in 10 oöphorectomised women. Despite the very high urinary oestrogen levles obtained, there was no significant change found in the other parameters during and after treatment. These findings are discussed, as is the significance of the metabolism of both endogenously produced and orally administered oestrogens in the menopausal woman."

J Thromb Haemost. 2014 Mar 15.

"The hemostatic profile of women using CEE is more prothrombotic than that of women using E2. These findings provide further evidence for a different thrombotic risk for oral CEE and oral E2."

Minerva Med. 2013 Apr;104(2):161-7.

"Estradiol itself has a lower impact on estrogen-hepatic proteins, and is more readily metabolized by the liver than ethinyl estradiol, the ethinyl group on which slows down that process. The structure increases the bioavailability of ethinyl estradiol compared with E2, but may also contribute to an increased likelihood of estrogen-related adverse events.40 »

Minerva Ginecol. 2014 Feb;66(1):91-102.

"Micronized estradiol (E2) and its estere valerate (EV), is more easily metabolized by the liver than ethynylestradiol (EE). This causes minimal metabolic impact »

"In comparison to EE/levonorgestrel (LNG), EV/DNG is more neutral on metabolism and coagulation"

"E2/NOMAc is more neutral than EE/LNG on metabolism and more neutral than EE/DRSP on coagulation"

Its also more effective since the liver breaks down part of it.

Sublingually, there is still some estradiol that inevitably gets swallowed. And quick peaks and valleys may cause neurological symptoms. I found no difference between either route in terms of effects on feminization, breast growth or well-being. Sublingual can be inconvenient and a pain in the a?&. Orally, it's easier.

If there is estrogen in the digestive tract the liver presumes a leak and raises clotting factors.

The reason clotting factors and proteins get modified is due to the triggering of estrogen receptors in the portal vein, from the intestines to the liver.

[Laura_7]

Can you point to studies where bio-identical estradiol strains the liver?

I'm talking from a purely technical point of view.
The liver has to work to break down parts of estrogen. Sublingual use is more effective.
So a part of the estrogen is broken down, in part to some unwanted forms like estrone.

If you have a motor that has to work that puts a certain strain on it.

By pure deduction the strain from non bioidentical substances would be greater because the normal effects do not run as smoothly, and having more and possibly unwanted byproducts.

Sublingually, there is still some estradiol that inevitably gets swallowed. And quick peaks and valleys may cause neurological symptoms. I found no difference between either route in terms of effects on feminization, breast growth or well-being. Sublingual can be inconvenient and a pain in the a?&. Orally, it's easier.

This contradicts

The reason clotting factors and proteins get modified is due to the triggering of estrogen receptors in the portal vein, from the intestines to the liver.

Sublingually those estrogen receptors are much less triggered therefore there are much less clotting factors.

People react differently to rising and falling levels.
Basically its a menopausal effect a few times a day if times of intake are too far from each other.
Someone described it as feeling testo creeping in.


*hugs*
 

[KayXo]

I'm talking from a purely technical point of view.
The liver has to work to break down parts of estrogen. Sublingual use is more effective.
So a part of the estrogen is broken down, in part to some unwanted forms like estrone.

Some argue it doesn't make a difference because estrone converts to estradiol. I'm not so sure as high estrone levels can *perhaps* block estradiol at receptors.

If you have a motor that has to work that puts a certain strain on it.

Studies provided do not show liver to be adversely affected by oral E2. I found no studies where oral E2 harmed liver.

This contradicts

Sublingually those estrogen receptors are much less triggered thus much less clotting factors.

But since estradiol is quickly metabolized by body and does not recirculate through portal vein again and again, receptors are triggered to a lesser degree. Also, you may be unaware of this, but estradiol also improves certain parameters such as fibrinolysis, plasminogen-activator inhibitor, plasmin, fibrinogen which have the opposite effect on coagulation.

[Laura_7]

Some argue it doesn't make a difference because estrone converts to estradiol. I'm not so sure as high estrone levels can *perhaps* block estradiol at receptors.

There are endos who say estrone makes for unwanted effects. They say this is one reason why injections can be more effective.

Studies provided do not show liver to be adversely affected by oral E2. I found no studies where oral E2 harmed liver.

I'd agree its no real harm like in accumulation of byproducts.
After all its bioidentical.

But since estradiol is quickly metabolized by body and does not recirculate through portal vein again and again, receptors are triggered to a lesser degree. Also, you may be unaware of this, but estradiol also improves certain parameters such as fibrinolysis, plasminogen-activator inhibitor, plasmin, fibrinogen which have the opposite effect on coagulation.

Nevertheless the passing through the liver breaks up estrogen in some unwanted forms. What is wanted is estradiol in the bloodstream.


*hugs*

[KayXo]

There are endos who say estrone makes for unwanted effects.

What unwanted effects? Are these corroborated by studies?

Nevertheless the passing through the liver breaks up estrogen in some unwanted forms. What is wanted is estradiol in the bloodstream.

But, it needs to be shown in studies, the adverse effects of these byproducts, and a causal relationship, not an association.

[Laura_7]

What unwanted effects? Are these corroborated by studies?

http://www.news-medical.net/health/Estrogen-Types.aspx

Oral estrogens are converted into estrone, with potential negative effects for the patient. This is not true for locally applied estrogen preparations like estrogen patch, creams, vaginal cream or estrogen given under the tongue.... The cause for this is that oral estrogens are metabolized by the liver and exert different effects than systemic estrogens, which are not metabolized by the liver.

Another difference between oral and system estrogen is regarding growth hormone (GH). GH is an important hormone made by the pituitary that stimulates the liver to produce another hormone called IGF-1 or Insulin like Growth factor 1. ...IGF1 has several beneficial effects, including an increase in energy and sense of well-being. It has recently been found that oral, but not systemic estrogen, blocks the effects of GH on stimulating IGF-1 at the liver. Oral estrogens thus can lead to high GH levels and also low IGF-1 levels. Both of these may have negative effects.


I hope the OP approves of the digression ... it may be interesting for some people 


*hugs*

[Hikari]

Twice per day sublingually as per my doctors orders....

[KayXo]

http://www.news-medical.net/health/Estrogen-Types.aspx

Regarding estrone being bad, which was what I asking about specifically, they say

"It has been postulated that estrone is a "bad" estrogen and may be the cause of estrogen's cancer-causing properties, while estriol is a "good" estrogen and may protect against cancer. Estradiol is probably neutral. There is no definite scientific evidence to prove this hypothesis however."

Oral estrogens are converted into estrone, with potential negative effects for the patient. This is not true for locally applied estrogen preparations like estrogen patch, creams, vaginal cream or estrogen given under the tongue.... The cause for this is that oral estrogens are metabolized by the liver and exert different effects than systemic estrogens, which are not metabolized by the liver.

They talk about potential negative effects of estrone on the patient without further elaborating.

The main difference between taking it orally vs non-orally is that
1) the ratio of estradiol going through the portal vein (where estrogen triggers estrogen receptors and modifies clotting parameters) to the estradiol circulating in the rest of the body is higher with oral administration such that clotting is affected to a greater extent BUT, as I pointed out with earlier studies, the risk of clotting remains quite low even with oral estradiol. The high levels of estrone during oral administration RELATIVE to estradiol also *may" be detrimental as estrone may BLOCK estradiol from binding to receptors (competitive binding) but this is not proven and some argue it makes no difference since estrone converts to estradiol.

Another difference between oral and system estrogen is regarding growth hormone (GH). GH is an important hormone made by the pituitary that stimulates the liver to produce another hormone called IGF-1 or Insulin like Growth factor 1. ...IGF1 has several beneficial effects, including an increase in energy and sense of well-being. It has recently been found that oral, but not systemic estrogen, blocks the effects of GH on stimulating IGF-1 at the liver. Oral estrogens thus can lead to high GH levels and also low IGF-1 levels. Both of these may have negative effects.

OK but that has nothing to do with estrone but rather the route of administration. Also, IGF-1 may have positive effects on increasing lean mass, reducing body fat, increasing skin thickness, perhaps increasing energy BUT it also promotes increased proliferation of cells and although fine for younger individuals such as children and adolescents who are growing, in older individuals, it may increase the risk of mutations and emergence of cancerous cells. On the other hand, estrogen taken non-orally may only have a slight effect on IGF-1, thus preventing the harm that could occur from too high levels of IGF-1 while allowing for the beneficial effects. If this is so, non-oral estrogen as opposed to oral estrogen may prove advantageous. I agree.

[Mariah]

Once every 10 days for estrogen and twice daily on the spiro. Hugs
Mariah

[andreapdenver]

Take spiro twice a day and estrogen once per day.

[Vii]

Sublingual intake isn't considered oral, is it?
Prior to my last checkup I've been taking sublingually every 8 hours and the result was pretty much that I had enough estrogen for about 7 transwomen in my blood and estron was even more ridiculously through the roof (the lab actually double-checked with a different method cause apparently they were surprised too). My endo wasn't very informative besides that my E is a "bit high"
The ratio was close to 2 units estron for every unit estrogen, which surprises me considering sublingual intake shouldn't be different to using patches to my knowledge? And now you girls post about estron being bad...

I'm not exactly sure how to control my levels if they explode like that, been thinking about cutting the pills into QAURTERS, on the other hand I noticed I don't feel so good if I cut my dosage even further back than I already did.

Back when I took valerate as oral estrogen my estron levels were about a quarter of what they're at now and 1/8th of the estrogen (And the levels were just fine). Should I perhaps switch back to valerate or just half my current dose? I can unfortunately not see another endo who would recommend dosages to me.

[KayXo]

Prior to my last checkup I've been taking sublingually every 8 hours and the result was pretty much that I had enough estrogen for about 7 transwomen in my blood and estron was even more ridiculously through the roof (the lab actually double-checked with a different method cause apparently they were surprised too).

Sublingually, your levels peak soon after taking but significantly drop within just 3-4 hours. No point in measuring, levels fluctuate so much. Levels in pregnant women get up to 75,000 pg/ml estradiol. My levels range from 1,000-4,000 pg/ml. When you say estrogen, I assume you mean estradiol because estrogen is the sum of estradiol +estrone.

The ratio was close to 2 units estron for every unit estrogen, which surprises me considering sublingual intake shouldn't be different to using patches to my knowledge?

There is a difference. You will inevitably swallow some, making for higher estrone levels.

I'm not exactly sure how to control my levels if they explode like that, been thinking about cutting the pills into QAURTERS, on the other hand I noticed I don't feel so good if I cut my dosage even further back than I already did.

Back when I took valerate as oral estrogen my estron levels were about a quarter of what they're at now and 1/8th of the estrogen (And the levels were just fine). Should I perhaps switch back to valerate or just half my current dose? I can unfortunately not see another endo who would recommend dosages to me.

These need to be discussed with your doctor. Sorry.

High levels aren't a gauge of health risks but sadly, few doctors get this.

[Vii]

Sublingually, your levels peak soon after taking but significantly drop within just 3-4 hours. No point in measuring, levels fluctuate so much. Levels in pregnant women get up to 75,000 pg/ml estradiol. My levels range from 1,000-4,000 pg/ml. When you say estrogen, I assume you mean estradiol because estrogen is the sum of estradiol +estrone.

Whops, I meant estradiol, yes. But the blood was taken some 4 hours after I took my dose. 1000-4000 pg/ml though, holy cow. That's even beyond what I had.

High levels aren't a gauge of health risks but sadly, few doctors get this.

Well I hope so, but thanks for reassuring.