Will a lose dose of estrogen limit changes

[tesseract49]

Hi everyone. I am Susan. I am a transwoman and have been on HRT for nearly 5 weeks. I was wondering, If someone were to take a low dosage of estrogen, would it still make all of the changes that a high dose would make but just take longer? Or would taking a low dose limit certain changes such as breast growth. I suppose what I am asking is that if someone was non-binary and didn't want breasts but still wanted to transition, is there a way that they could do it?  I am just asking out of curiosity, since I know some people who feel like that. Thanks very much xxx

[LordKAT]

I think it is a matter of YMMV. For some a little is plenty, for some full speed ahead and little effect.

[iKate]

It depends on you and your genes.

[Randi]

Older CIS men who are a bit overweight frequently grow breasts.  Testosterone can convert to estradiol by the action of the enzyme aromatase.

As we age men and women grow to resemble each other.  Low dose HRT may make things happen a bit slower, but the changes WILL happen.

[Ms Grace]

I know someone on low E and they have been very blessed by the boob fairy. There is no way to tell beforehand, it is largely genetic and how well the body responds to the HRT. In any case medication should be take with medical supervision. If you want less of an effect you should talk with your doctor.

[Jasper93]

Hi everyone. I am Susan. I am a transwoman and have been on HRT for nearly 5 weeks. I was wondering, If someone were to take a low dosage of estrogen, would it still make all of the changes that a high dose would make but just take longer? Or would taking a low dose limit certain changes such as breast growth. I suppose what I am asking is that if someone was non-binary and didn't want breasts but still wanted to transition, is there a way that they could do it?  I am just asking out of curiosity, since I know some people who feel like that. Thanks very much xxx

I have a medical background and can confirm that all changes brought on by HRT are mediated, not by the amount/delivery of estrogen that you are taking, but rather by the estrogen levels measured in your bloodstream.

So, e.g., I have always taken estradiol, spiro, and finasteride each day.  The estradiol dosage is notably low, but my estrogen levels are just short of 200 ng/dl, which is right where I need to be.  Thus, over time, I will see (and have seen) probably the maximum degree of changes that I should expect -- right on par with a few of my friends who take more estradiol/day.

Of course, there are other variables, such as human growth hormone -- usually mediated by how young/fit you are -- and this plays a pretty significant role in factors relating to breast growth.

Someone who wanted to transition without developing breasts would probably be hard-pressed to do so if they didn't want any breast growth, but I mean, if they started in like their 40s or so, I could see a relatively small amount of breast tissue developing.

Ally

Moderators note: Sorry Ally its against ToS 8 (c) to table dosages... taa.

[Jasper93]

I have a medical background and can confirm that all changes brought on by HRT are mediated, not by the amount/delivery of estrogen that you are taking, but rather by the estrogen levels measured in your bloodstream.

So, e.g., I have always taken estradiol, spiro, and finasteride each day.  The estradiol dosage is notably low, but my estrogen levels are just short of 200 ng/dl, which is right where I need to be.  Thus, over time, I will see (and have seen) probably the maximum degree of changes that I should expect -- right on par with a few of my friends who take more estradiol/day.

Of course, there are other variables, such as human growth hormone -- usually mediated by how young/fit you are -- and this plays a pretty significant role in factors relating to breast growth.

Someone who wanted to transition without developing breasts would probably be hard-pressed to do so if they didn't want any breast growth, but I mean, if they started in like their 40s or so, I could see a relatively small amount of breast tissue developing.

Ally

Moderators note: Sorry Ally its against ToS 8 (c) to table dosages... taa.

Now, that's -- that's just spankin' wonderful.

[katrinaw]

I started late (late forties/early fifties) on MTF suggested min dosages and have attained 34~35 B cup... happy as, got there after about 3 years, since then just rounding out..

As said before its about how your body works, its Endo System and metabolism... and of course your genealogy.

L Katy 

[FrancisAnn]

I have a medical background and can confirm that all changes brought on by HRT are mediated, not by the amount/delivery of estrogen that you are taking, but rather by the estrogen levels measured in your bloodstream.

So, e.g., I have always taken estradiol, spiro, and finasteride each day.  The estradiol dosage is notably low, but my estrogen levels are just short of 200 ng/dl, which is right where I need to be.  Thus, over time, I will see (and have seen) probably the maximum degree of changes that I should expect -- right on par with a few of my friends who take more estradiol/day.

Of course, there are other variables, such as human growth hormone -- usually mediated by how young/fit you are -- and this plays a pretty significant role in factors relating to breast growth.

Someone who wanted to transition without developing breasts would probably be hard-pressed to do so if they didn't want any breast growth, but I mean, if they started in like their 40s or so, I could see a relatively small amount of breast tissue developing.

Ally

Moderators note: Sorry Ally its against ToS 8 (c) to table dosages... taa.

Thanks, that's nice to see. My blood levels seem to be good & I've had some very nice improvements. My E level is normal I guess. I do not think we are suppose to post details but a higher level makes me feel better.

[KayXo]

my estrogen levels are just short of 200 ng/dl

Are you sure it's not pg/ml? Because 200 ng/dl is equal to 2,000 pg/ml.

Thus, over time, I will see (and have seen) probably the maximum degree of changes that I should expect

How can you be so sure? Perhaps a higher level, a stronger inhibition of androgen, the addition of a progestogen would bring about more changes. I'm not suggesting you do all those things but I'm just saying you can't be certain that this is the maximum degree of changes you will experience, that you have reached your genetic potential. I thought I had reached my maximum until I switched to injections and added progesterone which brought about many positive changes.

[LeaP]

It's helpful to understand a few basics about sex hormones.  First, everyone has both estradiol (E2) and testosterone (T) in their systems, male or female.  (I know ... everyone knows this).  What most don't realize is how potent E2 is.  It is, in fact, estimated at approximately 100 times stronger than T.  The amount of free (or unbound) E2 and T in your blood is actually pretty difficult to measure accurately and typical tests are subject to all kinds of errors, but in general, a male has about 10-20 times as much free T as E2.  A pre-menopausal woman's E2 varies over a huge range during her cycle, but even using the Endocrine Society's target (for trans women) of 200 pg/ml, taken as a reasonable average, she has roughly 10-20 times as much free E2 as T. 

Now think about that for a second.  If E2 is 100 times more potent than T, why aren't men estrogen dominant?  After all it appears that they don't have enough T to remain testosterone dominant, even at 20 times the concentration vs. E2.  The answer is simple.  Serum levels of free hormones are only part of the picture.  Men not only have more unbound testosterone than women in their blood, they produce - and consume - vastly larger quantities of it.  Men's bodies are bathed in the stuff.  If you think of men's bodies and women's bodies as water tanks, the "woman tank" is being filled with a small T hose, and drained with a small hose.  The "men's tank" is being filled with a fire hose and drained with a sewer pipe.  The respective levels in the tank don't give the whole picture! 

So once in a while you will run across a knowledgeable physician who will say that anti-androgens are more important to feminization than the female sex hormones.  And - not quibbling about exceptional circumstances - that is correct.  It isn't that knocking down T feminizes - it's that short-circuiting the production (and consumption) of T allows the E2 to do its thing.  Sufficiently suppress T and almost any reasonable dosage of E2 will do.  E2 is strong stuff.  Both limiting production and consumption of T are important.  Spiro's primary action is to prevent metabolism of T, but does have a weak inhibitory action on its production also.  Get T and E2 balances to the right tipping point, however, and the E2 can shut down production on its own.  Modern practice isn't to provide sufficient E2 dosing for that, but a combination of anti-androgens and E2 dosing accomplishes the same thing.

The next thing to know is that androgen and estrogen receptors not only vary in individuals for genetic reasons and by tissue type, they also vary in sensitivity.  The latter is partly luck of the draw genetically, but is heavily influenced by hormonal balance.  Receptors are said to up-regulate (become more sensitive) or down-regulate (less sensitive).  If, say, you happen to have few estrogen receptors in your breast tissue, AND they aren't terribly active AND can't be made so, no amount of E2 dosing is going to give you breasts.  And guess what?  There's no way to know in advance. 

Because the receptors you have are the receptors you have, and their sensitivity is what it is, your body can only consume a certain amount.  Where does any unconsumed by your receptors go?  Right down the toilet. Oh, and the half-life of E2 in your system is pretty short ... so it's a crapshoot as to whether or not you are getting an optimal dosage. 

So, Miss T looks at the facts and thinks: "OK, I'll block the T, that's easy enough, and I'll just mega dose the E2!"  BIG problem!  Forget the side-effects that everyone knows about for a second - the clots and liver damage and the like - remember that little bit about up and down regulation?  It turns out that too much E2 down-regulates estrogen receptors!  Whoops.  More is most definitely not better.  BUT (big but), once again, no-one knows what is too much or too little for YOU. 

The bottom line of the T and E2 story is that if you are getting results with good suppression of the first and low to reasonably low dosages of the second, you are highly likely to be in the position of your body consuming something close to the max possible E2 anyway.  If you are not, you MAY need modestly higher dosages, but it's equally likely that they will do no good.  Some say the most accurate way to measure what your body is actually doing with the hormones is to measure the levels in URINE, not blood.  That can be done... but is impractical and expensive, as you have to measure changing levels throughout the day.  If you think a once or twice yearly snapshot of unbound serum levels, using the typical test methods, is giving you and your doctor anything more than the grossest of indications, you would be dead wrong. 

As for progesterone ... another topic!

[Rachel]

Hi Susan,

You can not target where the E will effect. It is up to T suppression and adequate E to feminize.

A method is to measure areas now and in 3 month increments. Keep a record and you can graph the results for a visual indicator.

Keep in mind the longer you are away from puberty up to around age 30 the slower the results will be. 30 on up will have similar feminization rates, but YMMV. 

Keep in mind you may have a different perspective on transitioning in 2 months.

Enjoy the change.

[KayXo]

androgen and estrogen receptors not only vary in individuals for genetic reasons and by tissue type, they also vary in sensitivity.

The number of receptors ALSO varies in time AND is strongly regulated by hormonal "milieu. Depending on the number of receptors at any given time and on your genetics, cells will respond accordingly. Also, other factors such as growth hormone levels, stress levels, diet will affect response.

Progesterone downregulates estrogen receptors, estrogen upregulates progesterone receptors.

If, say, you happen to have few estrogen receptors in your breast tissue, AND they aren't terribly active AND can't be made so, no amount of E2 dosing is going to give you breasts.  And guess what?  There's no way to know in advance.

Receptors are in constant flux, not stable across time. The body is also in state of flux. There is of course a limit but in order to know that limit, I personally think it's worthwhile to intelligently and safely regulate regimen over time, change if need be, etc. with the approval of a doctor. I've been quite surprised at how changing to injections and adding progesterone has made such a significant difference in breast growth and feminization.

Forget the side-effects that everyone knows about for a second - the clots and liver damage and the like

This is mostly the case with oral estrogens that are NOT bio-identical. If you deal with estrogen that is bio-identical, the risks remain extremely low, more so if taken non-orally so I think it's worthwhile to try with doctor (if willing) higher doses if lower doses do not produce good results.

- remember that little bit about up and down regulation?  It turns out that too much E2 down-regulates estrogen receptors!  Whoops.  More is most definitely not better. 

In my case, more WAS better! And health is great, if not better than it was before. My levels are in the thousands of pg/ml. I know of other transwomen in the same situation as me. This may not be the case for all, as everyone varies but still, it can happen. Don't be so absolute.

The bottom line of the T and E2 story is that if you are getting results with good suppression of the first and low to reasonably low dosages of the second, you are highly likely to be in the position of your body consuming something close to the max possible E2 anyway.

Wrong again. It may be the case that some will not benefit from more but some may do, like me. Again, don't assume this is true for everyone. My experience and that of several other women says otherwise.

As always, anything you do must be done under the supervision of a competent doctor but I thought it was imperative of me to share my experience as it surely doesn't reflect the author's assertions. INDIVIDUALS VARY.

[LeaP]

Responses inline.

The number of receptors ALSO varies in time AND is strongly regulated by hormonal "milieu. Depending on the number of receptors at any given time and on your genetics, cells will respond accordingly. Also, other factors such as growth hormone levels, stress levels, diet will affect response.

Can you provide a reference to receptors increasing/decreasing in number, please?  (Unless you are simply referring to tissue growth.)

...

Receptors are in constant flux, not stable across time. The body is also in state of flux. There is of course a limit but in order to know that limit, I personally think it's worthwhile to intelligently and safely regulate regimen over time, change if need be, etc. with the approval of a doctor. I've been quite surprised at how changing to injections and adding progesterone has made such a significant difference in breast growth and feminization.

I agree, though I also think caution is in order (referring to dosages here).  I'm interested in trying injection, for example, but have a serious problem with needles.  (The last time they tried drawing blood at the doctors office, they wound up sending me to the hospital.  Another time - AT the hospital for a test, they had to send for an Oncology nurse to set an IV.) 

The reason I tried pushing off progesterone to another topic is that it raises different growth issues.  Progesterone does indeed increase growth for some (as well as shape maturation).  The point is more how it does it. Progesterone (among other things) builds the temporary milk producing duct and related gland structures in the breast for lactation.  Those almost always disappear over time when lactation stops (or pregnancy terminates).  What remains might be some additional fat deposits, some sag, and areola changes.  Over time, one is often left with little size change.  This is consistent with the results of a few I know who have dived into the world of "pregnancy level hormones."  Progesterone is also well-known for causing mood issues (depression in particular) and triggering unwanted hair growth.  Personally, I'm not interested in the risks.  If I had less growth on E alone, though ... who knows? 


This is mostly the case with oral estrogens that are NOT bio-identical. If you deal with estrogen that is bio-identical, the risks remain extremely low, more so if taken non-orally so I think it's worthwhile to try with doctor (if willing) higher doses if lower doses do not produce good results.

I don't think its that clear, frankly.  Much of the literature on the problems associated with estrogens do come from early studies and trials where various conjugated estrogens were used.  They mostly, out of the lack of knowledge of the times, involved very large dosages.  Much of the info on clotting, for example, comes from early ethinyl estradiol studies that resulted in astronomical serum levels.  Ditto regarding equine estrogens and even early birth control formulations.  There were a lot of things being conflated.

In my case, more WAS better! And health is great, if not better than it was before. My levels are in the thousands of pg/ml. I know of other transwomen in the same situation as me. This may not be the case for all, as everyone varies but still, it can happen. Don't be so absolute.

I'll say this in the nicest possible way.  I think you are out of your mind.    And yes, I'm fully aware that a lot of people do it.  And every medical authority, practice guideline, and care standard on the planet opposes it.  Aside from the older studies still referenced in regard to clotting issues, there are plenty of other reasons to avoid such high levels, not the least of which is the increase in cancer-causing metabolites produced in metabolizing the excess.  You may be exception to the rule.  If so, good for you.  But you're advocating an extreme.  Finally, risks pertain to future possibilities, not current health and results.  Cancer in 10 years, etc. (or whatever).


Wrong again. It may be the case that some will not benefit from more but some may do, like me. Again, don't assume this is true for everyone. My experience and that of several other women says otherwise.

I sincerely hope you never experience any fallout from your regimen.  Still, in the context of my remarks, "more" is a relative term - i.e., meaning more than you can process or that you need.  Alternatively, more to the point where it become self-defeating in a variety of possible ways.  While my post shows my bias toward low dosages - and not just for safety - if you read it carefully, the YMMV message is there as well. 

As always, anything you do must be done under the supervision of a competent doctor but I thought it was imperative of me to share my experience as it surely doesn't reflect the author's assertions. INDIVIDUALS VARY.

They do indeed.  It is you, however, that is advocating to the extreme. 

The comment on competent doctors is interesting in its own right.  HRT for trans people is off-label.  The guidelines and standards used by various organizations were developed from a combination of clinical practice observations and the application of general knowledge from research primarily involving females.  Any garden-variety GP should be competent enough to monitor serum hormone levels, liver enzymes, prolactin, potassium, and a few other things of basic interest to a trans patient.  But even an excellent endocrinologist is groping in the dark to some extent when you consider the stunning lack of research, any research - never mind long-term, peer-reviewed, double blind studies - on the effects, good, bad, or indifferent, of cross-sex hormone administration. 

[katiej]

There has been a lot of scientific information, so I'll add my anecdotal evidence.

I started on full dose spiro and low dose estradiol a bit more than 5 months ago.  I'm 37 and in good health, although a bit overweight.

The first change (a month or so after starting) I noticed was that I smell different.  My urine smells female, and I don't stink when I sweat.  My breasts got sore and had a hard lump around the 2nd or 3rd month.  But I haven't had much growth since then, if any at all. 

My body hair grows more slowly, and on my legs it seems to be more sparse.  But it hasn't changed enough to make a real difference. 

I've had no mood swings, and haven't noticed any increased emotions.  Though, overall I do feel much better than I did before HRT.

Everyone is correct when they say that YMMV.  Some changes are inevitable, but genetics seem to be the biggest determining factor whether low dose or full dose.  For me, the low dose has given me time to make a clear-headed decision without being driven to transition by the crippling dysphoria that I used to have.

[LeaP]

Katie, I would refine your statement to say that genetics are the biggest determining factor to potential results.  Dosages have to be in a balanced regimen to maximize your potential.  Much of the discussion above is about the maddeningly complex, competing, interacting, and individual considerations that pertain to the second.

[KayXo]

Can you provide a reference to receptors increasing/decreasing in number, please?

Progesterone downregulates estrogen receptors, this is a VERY well known fact. Downregulates means decreasing. You even later stated that estrogen downregulates estrogen receptors so that receptors are constantly increasing or decreasing depending on other hormonal factors in the body.

https://www.glowm.com/resources/glowm/cd/pages/v5/v5c004.html

"The half-life of steroid hormone receptors ranges from 2 to 4 hours for ERα,155 4 hours for AR,157 7 to 10 hours for PR,158 and 19 hours for GR.159"

Progesterone (among other things) builds the temporary milk producing duct and related gland structures in the breast for lactation.  Those almost always disappear over time when lactation stops (or pregnancy terminates).

I don't intend to EVER stop/reduce progesterone so these structures (lobulo-alveolar) shall remain and not atrophy. I personally don't see a reason to stopping it.

Progesterone is also well-known for causing mood issues (depression in particular) and triggering unwanted hair growth.

Are you talking about progesterone or other progestogens such as medroxyprogesterone acetate? Progesterone and a few other progestogens (dydrogesterone, hydroxyprogesterone acetate) have absolutely no androgenic effects, these have been verified in several studies, they don't increase levels of androgen (my T levels have remained at around 20 ng/dl on high dose progesterone) nor are they androgen receptor agonists. This is why these can be safely prescribed to pregnant women who may have a female fetus.

Also, progesterone increases allopregnanolone which is known to be anxiolytic and anti-depressive due to GABA agonist activity. It actually makes me happy and some have testified its mood enhancing properties. Plenty of studies on that. Also depends on how much estrogen you are taking with it as P downregulates E.

Very important to differentiate between progestogens as their molecular structures differ and it makes a significant difference in terms of effects.

I think you are out of your mind.    And yes, I'm fully aware that a lot of people do it.  And every medical authority, practice guideline, and care standard on the planet opposes it.  Aside from the older studies still referenced in regard to clotting issues, there are plenty of other reasons to avoid such high levels, not the least of which is the increase in cancer-causing metabolites produced in metabolizing the excess.  You may be exception to the rule.  If so, good for you.  But you're advocating an extreme.  Finally, risks pertain to future possibilities, not current health and results.  Cancer in 10 years, etc. (or whatever).

Please provide evidence (studies) that show that high levels of bio-identical estradiol increase risk of coagulation and pulmonary embolism, cancer.

Breast cancer incidence in transsexual women is extremely rare (despite decades of aggressive treatment and researchers' interest in reporting such matters) and according to one of the leading authorities worldwide on transsexual treatment, Prof. Gooren, is the same as genetic males not on HRT. His original treatment was quite aggressive and consisted of high doses of ethinyl estradiol. Also, Harry Benjamin noted no incidence (in his book, The Transsexual Phenomena) among his transsexual patients in the 1960's although doses were VERY high by today's standards. VERY high! Finally, he includes a note from a urologist who treated thousands of men with prostate cancer patients with VERY high dosages of DES and observed no cancer from treatment in all his years of experience.

As to clotting, do consider the following:

- studies on men with prostate cancer wanted to observe coagulation (and cardiovascular) changes under high dosages of patches and injectables (bio-identical estradiol), with levels ranging from 400-700 pg/ml. The median age was 75 and the oldest man was 91. As you know, health risks increase significantly with age. And, yet, health risks were NOT increased. In fact, one article concluded that this treatment had a protective effect towards thrombosis.
- pregnant women experience levels up to 75,000 pg/ml, several orders higher than my levels. Absolute risk of DVT in pregnant women is 0.05-0.2%. Some women are pregnant several times during their lives.

The only randomized controlled study that noted an increase in breast cancer risk (but decrease in colon cancer risk) was in women treated with conjugated equine estrogens AND medroxyprogesterone acetate. Those treated with only estrogen had a decreased incidence of breast cancer risk. Also, clotting increased, more on the combo HRT because both these are NOT bio-identical and have an exaggerated tendency to increase coagulation.

I personally know transwomen who, on ethinyl estradiol, developed DVT but later upon switching to injectable bio-identical estradiol had no recurrence after several years, although doses were quite high.

I can gladly provide all references to you, in private, if you wish.

I've been on hormones for 10 years + and in most of those years, on moderate to high doses of estrogen.

It is you, however, that is advocating to the extreme.

I'm not advocating extremes. I'm simply suggesting that if development is less than satisfactory on lower doses, then I personally think that higher doses may prove beneficial for SOME, should the doctor be onboard. I don't consider risks from higher doses significant due to current evidence available. I'm not a doctor but I have spent thousands of hours reading full studies, speaking with doctors and transsexual women worldwide. This is my opinion. You do your own research, speak with doctors and make your own conclusions. It's important to not simply accept assertions, take a proactive approach and remain critical. Read the studies, the literature, question. We, as transsexuals, have been told several things about hormones but it is up to us to verify this information on our own; doctors also disagree...some don't mind prescribing higher doses while some refuse to do so. Find out for yourself and discuss with your doctor(s).

even an excellent endocrinologist is groping in the dark to some extent when you consider the stunning lack of research, any research - never mind long-term, peer-reviewed, double blind studies - on the effects, good, bad, or indifferent, of cross-sex hormone administration.

I agree on some points but if one takes the time to really review the research, including studies on transsexual, ciswomen and men with prostate cancer patients, read anecdotal evidence from thousands of transsexual women worldwide in forums, one starts to get a pretty good idea. I think, sadly, many doctors don't have the time to do the research and have, obviously, not been trained in university to treat such a unique population. We can bring something to the table. I have and my doctors have always appreciated my input. I am under the supervision of my family physician and a reputable endocrinologist from Cambridge with decades of experience with transpeople. They have no problems with my current regimen as I proposed it.  

[LeaP]

Progesterone downregulates estrogen receptors, this is a VERY well known fact.

Yes, I mentioned regulation.  I was asking about your comment about the NUMBERS of receptors, which is completely different.  As far as I'm aware, the receptor sites still exist, but have more or less affinity depending on regulation.

Will go through the rest of your thoughtful answer later.  Thanks!

[Ms Grace]

This is becoming a medical ping pong session, I think the question has well and truly been answered - locking the thread.