Gene Devine
Super Moderator
I wrote this paper some time ago and thought it may be of help to some of you where elevated E2 may be a problem and where your Doctor is not trained correctly. Some of you may recognize this from my past but nevertheless, it's still very relevant.
Estradiol and Therapeutic Management: What you should know – By Gene Devine
From the beginning...
Estradiol is simply a class of Estrogen of which there are about 30 different types. Estradiol (E2 or 17β-Estradiol, or as Oestradiol) is a sex hormone. Estradiol is abbreviated as “E2” as it has 2 hydroxyl groups in its molecular structure. It is known by many of us as simply “E2 “as its abbreviation.
Many people (even Physicians) simply call Estradiol, Estrogen.
Estradiol is the major sex hormone of interest in foundational Testosterone Replacement Therapies.
Why it Matters
There are basically two very important reasons that we need to care about Estradiol.
The first is that Estradiol is a powerful Testosterone receptor antagonist. What this means to us men is that Estradiol creates a very strong bond to the Androgen Receptors of Testosterone and renders them useless.
However, when testosterone binds to an Androgen Receptor, it activates that receptor and we get the physiological effects we're all looking for. Now, when Estradiol binds to that same receptor it blocks Testosterone from binding, yet it does not activate the receptor, so in short nothing happens.
This means that if your Estradiol serum level is high, no matter how much exogenous testosterone you take it isn't going to help you as it should because too many of your androgen receptors are now blocked by Estradiol and your Free Testosterone has nowhere to go.
Exogenous Testosterone can't do you any good if it doesn't have receptors available to activate…simple enough.
Now, things can get worse believe it or not... some believe that elevated levels of Estradiol can cause the down regulation of Androgen Receptors. What this potentially means is that your body may respond to higher levels of Estradiol by creating fewer Androgen Receptors as cells are replaced in a normal regeneration cycle.
So, not only does Estradiol block the available Androgen Receptors as noted, it may cause your body to produce fewer of them in the future!
This is where many Docs get it wrong and is one primary reason why just “raising Testosterone serum levels” alone as a mono-therapy may not have any immediate effect on a man. It may be that the receptors have been down regulated and so there will be a need to lower Estradiol levels and increase Testosterone levels in order to get a man’s body to up-regulate again and this could take some time.
The second reason we care about Estradiol in men is that we also have Estrogen Receptors and Estradiol will bind to them and cause them to activate. This is fine if you want to grow man boobs (Gynocomastia) add belly fat and get an enlarged prostate, among other things, but not so good if you want to look and feel like a healthy man.
Keep in mind, the aromatase enzyme lives in the skin and has a propensity for abdominal fat. Meaning the more belly fat you have the higher level of aromatase you will have.
Where Estrogen Comes From
Let’s forget environmental estrogens here; the primary pathway for Estradiol production is via the conversion of Testosterone by the Aromatase Enzyme.
What this means is that the Aromatase Enzyme found in every man’s body bonds to Testosterone Receptors and chemically synthesizes it to Estradiol (E2).
Think about this for a minute and realize that this conversion is a double edged sword. All in one process you're 1) losing Testosterone and 2) gaining Estradiol.
Obviously this is not good healthy state to be in and one that needs to be managed correctly.
This is where drugs like an Aromatase Inhibitors (AI) like Anastrozole (brand name Arimidex - aka "adex" etc.) come into a well planned TRT protocol. An AI will bond to the Aromatase Enzyme and prevent it from converting your Testosterone to Estradiol.
Keep in mind, and many men get this wrong; but AI’s do not work directly on Estradiol nor on the Estrogen receptors. It is SERM's like Clomid and Nolvadex that bond to Estrogen Receptors.
SERM's and AI's are different compounds, so don't get them confused. Nolvadex acts as an estrogen antagonist and will not stop the aromatization process. It disrupts the estrogen receptor bond formation process. So, your estrogen will rise but will be blocked from the chest receptors.
So, an AI gives us that double edged sword but now in reverse. An AI will prevent the loss of Testosterone to conversion and consequently lowers our Estradiol levels which helps keep our Androgen Receptors available for Testosterone.
Keep in mind that Anastrozole is a powerful aromatase inhibitor (antagonist) and that too much can easily cause you to push your E2 level to low. Its half life is app. 46.8 hrs so this needs to be kept in mind upon initiating a dosing schedule, especially if self-administering this product. In most all cases it is suggested to start with the lowest possible dose and titrate up based on frequent blood work, until stable levels are attained.
Less is more here! Both high and low E2 come with similar side effects such as joint pain, loss of libido, etc.
Estradiol Always Follows Testosterone
Here's where Doctor’s and other Medical Practitioners get it wrong; they forget that Estradiol always follows Testosterone. As your Testosterone serum levels elevate, so will your Estradiol levels.
If your Doctor is not doing something to manage your Estradiol levels (like taking an AI) then you aren't really going to get anywhere with higher Testosterone serum levels because your higher Estradiol levels are just going to cancel out any beneficial effect from the Testosterone. Like I said, your exogenous Testosterone can't do you any good if all your Androgen Receptors are all bound up with Estradiol.
For those of us with "age related" low Testosterone levels, this is a serious issue because our bodies are naturally trying to keep Testosterone levels lower and Estradiol higher by producing more of the Aromatase Enzyme.
If you're a younger man and have low Testosterone serum levels for some other reason, Aromatization may not be as much of an issue, but trust me…it still matters. Keep in mind that many fifty plus year old men have higher estrogen levels than women the same age.
Fat!
Excessive body fat produces Estrogen and Aromatase Enzymes. If you're carrying extra body fat, one of the best things you can do to help your hormone balance is to lose that fat…and for many other health reasons as well.
Problems Associated With Low Estradiol
What is the ideal number for you? That would be for you and your physician to decide. However, keep in mind, there can be just as many complications, if not more, by having your estradiol value too low. It is essential for men to have healthy levels of estrogen in their bodies to function properly.
Some have the mindset that lower is better, which is the wrong type of mindset. In fact, sustaining low levels of estradiol for lengthy periods of time can be downright detrimental!
Here are just some of the issues associated with having your estradiol level too low:
• A feeling of being lethargic, sluggishness, and frequently fatigued.
• Headaches
• Depression
• Dry skin and hair
• Unhealthy nails
• Loss of libido
• Sore, achy joints
• Inability to concentrate
• Panic and anxiety sensations
• Potential risks for osteoporosis and bone fractures
• Potential cardiovascular and immune risks
“In Range” Does Not Mean “Normal”
One of the biggest and more frustrating problems you're likely to face is the problem of most Doctors believing that any blood test value that is "in range" is "normal" and therefore “fine”. I wish it was that simple and that goes for most if not all lab ranges.
Let's take a look at Testosterone values. The Total Testosterone reference range for Quest is 250-1100 ng/dL. But those values were formulated simply by looking at the values of everyone else who has a blood test for Testosterone…let me say that again: “everyone else.”
What's normal for a young guy is to be in the higher end of the reference range. What's normal for an older guy is to be in the lower end of the range…just normal biological processes.
So, while low Testosterone might be "normal" from a lab reference range perspective that doesn't mean it's good or healthy for that matter! I may be an older guy, but why should I be happy with lower Testosterone and elevated Estradiol levels simply because “it's normal”?
All men of all ages should be in the higher end of the reference range if they want to feel good, look good and perform athletically and sexually as men and grow old healthy!
The same holds true for Estradiol levels. The Access Medical Labs reference range for Estradiol Sensitive is 7.6-42.6 pg/ml but "normal" young men are at the low end of that reference range and that's where we all want to be as well.
Trust me, if your Testosterone serum levels is 250 ng/dl and your Estradiol is 42 pg/ml, you may be "in range" for both values, but you aren't going to feel good or have anywhere near the athletic and sexual performance that you would have if your Testosterone level was 800 ng/dl and your Estradiol level was 25 pg/ml.
A word about Estradiol “Sensitive” Testing
Unless your Doctor specifically requests a ‘Sensitive’ assay the lab will default to the standard Estradiol assay designed specifically for women, which is useless for men. The reason for the difference between the two assays is the bell curve from which the test was designed sits within the “normal” range for women and not men.
Therefore, the hormone concentration range appropriate for adult men falls on the flat slope of that bell curve making it completely inaccurate for testing men’s E2 serum levels. Always, ask for the “Sensitive” assay when your Doctor is conducting a blood test and testing for Estradiol.
Natural Variation in Populations
All populations exhibit some amount variation. The average height for men might be 5' 10" but we all know guys who are much taller and much shorter…it’s just a natural part of our existence. This same variation applies to Testosterone serum levels, Estradiol serum levels, and reactions to various therapies as well…we’re all different!
In other words, while what I've outlined holds true in general; how it specifically applys to you will vary.
Ok, that's enough rambling from me for now on this subject matter. I wrote this as a basic primer; there's a lot more to this subject, so use this as a springboard to do more research on your own and learn.
Estradiol and Therapeutic Management: What you should know – By Gene Devine
From the beginning...
Estradiol is simply a class of Estrogen of which there are about 30 different types. Estradiol (E2 or 17β-Estradiol, or as Oestradiol) is a sex hormone. Estradiol is abbreviated as “E2” as it has 2 hydroxyl groups in its molecular structure. It is known by many of us as simply “E2 “as its abbreviation.
Many people (even Physicians) simply call Estradiol, Estrogen.
Estradiol is the major sex hormone of interest in foundational Testosterone Replacement Therapies.
Why it Matters
There are basically two very important reasons that we need to care about Estradiol.
The first is that Estradiol is a powerful Testosterone receptor antagonist. What this means to us men is that Estradiol creates a very strong bond to the Androgen Receptors of Testosterone and renders them useless.
However, when testosterone binds to an Androgen Receptor, it activates that receptor and we get the physiological effects we're all looking for. Now, when Estradiol binds to that same receptor it blocks Testosterone from binding, yet it does not activate the receptor, so in short nothing happens.
This means that if your Estradiol serum level is high, no matter how much exogenous testosterone you take it isn't going to help you as it should because too many of your androgen receptors are now blocked by Estradiol and your Free Testosterone has nowhere to go.
Exogenous Testosterone can't do you any good if it doesn't have receptors available to activate…simple enough.
Now, things can get worse believe it or not... some believe that elevated levels of Estradiol can cause the down regulation of Androgen Receptors. What this potentially means is that your body may respond to higher levels of Estradiol by creating fewer Androgen Receptors as cells are replaced in a normal regeneration cycle.
So, not only does Estradiol block the available Androgen Receptors as noted, it may cause your body to produce fewer of them in the future!
This is where many Docs get it wrong and is one primary reason why just “raising Testosterone serum levels” alone as a mono-therapy may not have any immediate effect on a man. It may be that the receptors have been down regulated and so there will be a need to lower Estradiol levels and increase Testosterone levels in order to get a man’s body to up-regulate again and this could take some time.
The second reason we care about Estradiol in men is that we also have Estrogen Receptors and Estradiol will bind to them and cause them to activate. This is fine if you want to grow man boobs (Gynocomastia) add belly fat and get an enlarged prostate, among other things, but not so good if you want to look and feel like a healthy man.
Keep in mind, the aromatase enzyme lives in the skin and has a propensity for abdominal fat. Meaning the more belly fat you have the higher level of aromatase you will have.
Where Estrogen Comes From
Let’s forget environmental estrogens here; the primary pathway for Estradiol production is via the conversion of Testosterone by the Aromatase Enzyme.
What this means is that the Aromatase Enzyme found in every man’s body bonds to Testosterone Receptors and chemically synthesizes it to Estradiol (E2).
Think about this for a minute and realize that this conversion is a double edged sword. All in one process you're 1) losing Testosterone and 2) gaining Estradiol.
Obviously this is not good healthy state to be in and one that needs to be managed correctly.
This is where drugs like an Aromatase Inhibitors (AI) like Anastrozole (brand name Arimidex - aka "adex" etc.) come into a well planned TRT protocol. An AI will bond to the Aromatase Enzyme and prevent it from converting your Testosterone to Estradiol.
Keep in mind, and many men get this wrong; but AI’s do not work directly on Estradiol nor on the Estrogen receptors. It is SERM's like Clomid and Nolvadex that bond to Estrogen Receptors.
SERM's and AI's are different compounds, so don't get them confused. Nolvadex acts as an estrogen antagonist and will not stop the aromatization process. It disrupts the estrogen receptor bond formation process. So, your estrogen will rise but will be blocked from the chest receptors.
So, an AI gives us that double edged sword but now in reverse. An AI will prevent the loss of Testosterone to conversion and consequently lowers our Estradiol levels which helps keep our Androgen Receptors available for Testosterone.
Keep in mind that Anastrozole is a powerful aromatase inhibitor (antagonist) and that too much can easily cause you to push your E2 level to low. Its half life is app. 46.8 hrs so this needs to be kept in mind upon initiating a dosing schedule, especially if self-administering this product. In most all cases it is suggested to start with the lowest possible dose and titrate up based on frequent blood work, until stable levels are attained.
Less is more here! Both high and low E2 come with similar side effects such as joint pain, loss of libido, etc.
Estradiol Always Follows Testosterone
Here's where Doctor’s and other Medical Practitioners get it wrong; they forget that Estradiol always follows Testosterone. As your Testosterone serum levels elevate, so will your Estradiol levels.
If your Doctor is not doing something to manage your Estradiol levels (like taking an AI) then you aren't really going to get anywhere with higher Testosterone serum levels because your higher Estradiol levels are just going to cancel out any beneficial effect from the Testosterone. Like I said, your exogenous Testosterone can't do you any good if all your Androgen Receptors are all bound up with Estradiol.
For those of us with "age related" low Testosterone levels, this is a serious issue because our bodies are naturally trying to keep Testosterone levels lower and Estradiol higher by producing more of the Aromatase Enzyme.
If you're a younger man and have low Testosterone serum levels for some other reason, Aromatization may not be as much of an issue, but trust me…it still matters. Keep in mind that many fifty plus year old men have higher estrogen levels than women the same age.
Fat!
Excessive body fat produces Estrogen and Aromatase Enzymes. If you're carrying extra body fat, one of the best things you can do to help your hormone balance is to lose that fat…and for many other health reasons as well.
Problems Associated With Low Estradiol
What is the ideal number for you? That would be for you and your physician to decide. However, keep in mind, there can be just as many complications, if not more, by having your estradiol value too low. It is essential for men to have healthy levels of estrogen in their bodies to function properly.
Some have the mindset that lower is better, which is the wrong type of mindset. In fact, sustaining low levels of estradiol for lengthy periods of time can be downright detrimental!
Here are just some of the issues associated with having your estradiol level too low:
• A feeling of being lethargic, sluggishness, and frequently fatigued.
• Headaches
• Depression
• Dry skin and hair
• Unhealthy nails
• Loss of libido
• Sore, achy joints
• Inability to concentrate
• Panic and anxiety sensations
• Potential risks for osteoporosis and bone fractures
• Potential cardiovascular and immune risks
“In Range” Does Not Mean “Normal”
One of the biggest and more frustrating problems you're likely to face is the problem of most Doctors believing that any blood test value that is "in range" is "normal" and therefore “fine”. I wish it was that simple and that goes for most if not all lab ranges.
Let's take a look at Testosterone values. The Total Testosterone reference range for Quest is 250-1100 ng/dL. But those values were formulated simply by looking at the values of everyone else who has a blood test for Testosterone…let me say that again: “everyone else.”
What's normal for a young guy is to be in the higher end of the reference range. What's normal for an older guy is to be in the lower end of the range…just normal biological processes.
So, while low Testosterone might be "normal" from a lab reference range perspective that doesn't mean it's good or healthy for that matter! I may be an older guy, but why should I be happy with lower Testosterone and elevated Estradiol levels simply because “it's normal”?
All men of all ages should be in the higher end of the reference range if they want to feel good, look good and perform athletically and sexually as men and grow old healthy!
The same holds true for Estradiol levels. The Access Medical Labs reference range for Estradiol Sensitive is 7.6-42.6 pg/ml but "normal" young men are at the low end of that reference range and that's where we all want to be as well.
Trust me, if your Testosterone serum levels is 250 ng/dl and your Estradiol is 42 pg/ml, you may be "in range" for both values, but you aren't going to feel good or have anywhere near the athletic and sexual performance that you would have if your Testosterone level was 800 ng/dl and your Estradiol level was 25 pg/ml.
A word about Estradiol “Sensitive” Testing
Unless your Doctor specifically requests a ‘Sensitive’ assay the lab will default to the standard Estradiol assay designed specifically for women, which is useless for men. The reason for the difference between the two assays is the bell curve from which the test was designed sits within the “normal” range for women and not men.
Therefore, the hormone concentration range appropriate for adult men falls on the flat slope of that bell curve making it completely inaccurate for testing men’s E2 serum levels. Always, ask for the “Sensitive” assay when your Doctor is conducting a blood test and testing for Estradiol.
Natural Variation in Populations
All populations exhibit some amount variation. The average height for men might be 5' 10" but we all know guys who are much taller and much shorter…it’s just a natural part of our existence. This same variation applies to Testosterone serum levels, Estradiol serum levels, and reactions to various therapies as well…we’re all different!
In other words, while what I've outlined holds true in general; how it specifically applys to you will vary.
Ok, that's enough rambling from me for now on this subject matter. I wrote this as a basic primer; there's a lot more to this subject, so use this as a springboard to do more research on your own and learn.
