Second test confirmed my E2 is extremely low... not on any AI. HELP!

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Soilsample

New Member
45 year old.
I'm not feeling any better than I felt before I began this T journey a year ago.... as a matter of fact I'm worse because I have ZERO SEX DRIVE.
Injecting 1ml Test Cyp 200 every 2 weeks in divided doses every 3.5 days.
Had blood tested on 1/12/17 (in trough before injection) with orders from discount labs.

Testosterone Free+Total, LC/MS - 933

Free Testosterone (direct) - 31.9

Estradiol, Sensitive- 5.3

Im not and never have used any AI.... so concensus here was to confirm testing because it might be a bad lab result.

Second set of labs pulled 1/24/17

Testosterone Free+Total, LC/MS - 501

Free Testosterone (direct) - 15.9

Estradiol, Sensitive- 6.4

My Doctor said "your Estrogen is a little low but you should be feeling fine"
he really doesn't have any ideas on fixing me and now wants me to try seeing an Endocrinologist....

PLEASE Help!
 
Defy Medical TRT clinic doctor

ERO

Member
First off, my 2-cents would be to pass on the Endo appointment as he or she is likely to tell you to quit TRT cold turkey for 2-3 months to establish a basline instead of doing anything useful.

Are you using HCG? If not, adding in 500IU every 3.5 days could help your E2 levels. If your doc won't prescribe it, Defy Medical has a HCG program for guys that are getting their TRT care elsewhere, but that need HCG.
 

Soilsample

New Member
I'm not currently using HCG, never have used it, but I do have some at home that I bought online when I started taking the Testosterone.
If I introduce the HCG into my protocol, how long would you guys suggest waiting before I have another blood test?

Thanks for for the advice!
 

HarryCat

Member
You pulled the second set of labs just before your injection, like the first set of labs, and your total T is half of what it was before? Something is wrong with that. You should not have that much variability.
 

MG123

New Member
If your estradiol is that low with a 933 total T without taking an AI, what in the world was it before starting TRT?

You should wait about a month before testing again after adding the hCG.
 
You're def doing something wrong, wild differences in Total and Free T between the two tests. You can't have any variances in your injection protocol, or when you have labs pulled, you have to do it all strictly the same time-after-time or you'll muck your results. I think you need to concentrate on getting your protocol and testing down before you try and address something else.
 

Soilsample

New Member
Thanks Vince,
My injection protocol is very solid. I inject Monday morning and Thursday night. Very consistently.

HOWEVER I'm a shift worker....
When the latest set of labs was drawn I had been due for my Monday injection but didn't want to mess up the results by injecting right before the draw, so I was actually over due for my injection and I injected right after the blood draw.
It may not make sense but it's the best I could do under the circumstances.
I always try to get my blood drawn on Thursday before my night time injecting but couldn't do it that way due to my work schedule.
 

Soilsample

New Member
MG....
My doctor never tested my Estrodiol. So I don't know what it was before the T treatment began. (Insert "idiot doctor" comment here)
Im planning to sign up with Defy as soon as possible but it might be a couple of months in the future.
 
I think the first one is a lab error, and the second one is just because your total is low.

I had a sensitive test that screwed up, came back at 3.1, and labcorp finally reran it, came back at 21. Ironically, I had an estradiol free ran, which includes a total E2 which is also a sensitive test, that came back at 28, and ordered standard E2 for curiosity and that was 21.

How long was your injection delayed before you got the labs drawn?
 

Soilsample

New Member
My normal injection is Monday morning. The blood draw was early Tuesday, so about 24 hours delay.

I understand it could be lab error but I don't feel any better on the testosterone, and my sex drive is worse than it was before it all began. Also my doctor tested "estrogen" 2 times over this same period and confirmed that "your estrogen is low"
 
My normal injection is Monday morning. The blood draw was early Tuesday, so about 24 hours delay.

I understand it could be lab error but I don't feel any better on the testosterone, and my sex drive is worse than it was before it all began. Also my doctor tested "estrogen" 2 times over this same period and confirmed that "your estrogen is low"

Okay but it makes perfect sense.

Your E2 was higher when testosterone was lower, which supports the lower E2 test being an error, and the second one being due to your testosterone decreasing.

The only other explanation is that you're aromatase deficient.
 
Until you inject and test with consistency, the hallmark of a successful protocol, you will have problems...no way around that. From some one that has worked every shift and overnite hours known to man kind while in the military, that's all an excuse on your part. I'm here to help you and not bash you...it's that important to success.
 

Vince

Super Moderator
Personally I need good DHEA levels to keep my E2 level in range. I use dhea to raise my E2, I wonder what your DHEA levels are sitting at?
 

Formula364

New Member
"Given how large an overlap there is between the symptoms of testosterone deficiency, thyroid hormone deficiency, cortisol deficiency, insulin resistance/diabetes, etc., it is important to look at the other hormones for a solution if total testosterone is at a good level." Are you diabetic? Know your SHBG #?

"How much estradiol (E2) is made depends a lot on how high total testosterone becomes and how much aromatase activity is present.

HCG use increases the production of aromatase - increasing estradiol production." As previously suggested w/DHEA.

"When Estradiol goes too low in a male, frequently sexual dysfunction and loss of competitive drive may occur. This is one marker for excessive dosing of an aromatase inhibitor. However, whether or not there is going to be such a negative effect depends on other signals and metabolism.

The sensitivity of each male to estradiol's effects will vary with the levels of other hormones, signals, and metabolic-nutritional status. For example, the estrogen signal, itself, may need adequate progesterone to stimulate the production of estrogen receptors. If hypothalamic-pituitary adrenal dysregulation is present, the estrogen signal is attenuated and symptoms of low estrogen may occur at higher levels. Additionally, thyroid hormone levels increase SHBG levels. The higher the SHBG, the higher the estradiol but less is free to function. Thus the estradiol signal is reduced despite the higher level. Once the other signal and metabolic-nutritional problems are addressed and signaling optimized in the other systems, the male may not have as large a negative effect from estradiol as prior to addressing the other problems first." You could also add Pregnenolone to aid in Progesterone which helps production of estrogen receptors. You haven't been using hCG, and your Preg levels are probably low.
 

Soilsample

New Member
Thanks for all the helpful comments!

I'm also struggling with low Thyroid activity and am in an ongoing test/adjust meds (levothyroxene) cycle with my general practitioner to fix the problem. My Thyroid labs from January 5 showed that my thyroid meds are "beginning to work" according to my doctor. Unfortunately I don't have the test number.

FYI my Sbgh was 16.8

The struggle with shift work isn't an excuse... I was trying to avoid having to wait another week for my blood draw so I chose to push back my injection for the sake of the test. I now realize that this was a mistake and I'll make sure that my blood work is always pulled on the morning of my Thursday night injection.
Again. Thanks for the help!
 

Formula364

New Member
T4 only is a pretty flaccid response (and common) from you Dr. It doesn't guarantee increased T3. Don't drive your DHEA levels too high.
Your SHBG is fairly low - a few points of interest:

"The most common cause of low SHBG is excessive insulin - i.e. insulin resistance. Insulin resistance in turn leads to a cascade of events which results other hormone imbalances such as low testosterone production, suboptimal thyroid hormone activity, adrenal fatigue, etc.

Factors which together in a balance determine SHBG are:
1. Anabolic hormones generally reduce SHBG. These include testosterone, DHEA, insulin, DHT, and growth hormone.
2. Thyroid hormone, Estrogens, and Progesterone (by increasing estrogen receptors/sensitivity), increase SHBG."

"Even with low SHBG - which is difficult to correct since it depends on the balance of so many hormones - when the other hormones and neurotransmitters are optimized, sex drive and the ability to have an erection can often return.

Increases SHBG:
Estrogens (particularly Estradiol)
Progesterone (by increasing Estrogen receptors)
Thyroid Hormone (particularly Hyperthyroidism)
Liver Disease
Anorexia, Starvation
Hypoglycemia (low insulin)

Reduces SHBG:
Insulin (and insulin resistance)
Testosterone
Growth Hormone
DHEA
Other Androgens
Obesity
Hypothyroidism
Excessive Cortisol (Cushing's Syndrome or Disease)
Progestins (such as by blocking progesterone's effects)

The primary purpose of a binding protein such as SHBG is to prolong the life of testosterone in the body. Otherwise, with a half-life of 10-100 minutes - testosterone would be almost totally eliminated from the body within 50 minutes to 8.3 hours without constant production or frequent application of testosterone." You need to investigate more frequent injections until you raise SBHG.

"The quickest way to increase SHBG is to treat a person with T3 (Cytomel) or to a lesser extent Armour Thyroid, when optimizing thyroid hormone signaling. This increases SHBG production from the liver. Optimizing thyroid signaling first is important to set the stage for subsequent testosterone treatment. Doing so helps correct low SHBG.

Low SHBG is one of many reasons testosterone levels are so low in diabetes type 2. When SHBG is low due to insulin resistance/diabetes type 2 and high insulin level, treatment with testosterone helps reduce insulin resistance. Over several months time, SHBG self-corrects as other metabolic improvements with testosterone treatment occur such as loss of belly fat. Of course, in the presence of diabetes type 2, one of the first things to do is to optimize thyroid hormone and treat the insulin resistance with medications such as Metformin or Actos. This would help improve SHBG and would set the stage for testosterone treatment, minimizing problems that can occur with testosterone treatment - such as anxiety, irritability, fatigue, excessive estrogen, etc."
 

Formula364

New Member
And some more helpful text from Dr. Mariano on TRT and Thyroid:

"Usually, when I start testosterone replacement therapy (TRT), I also have to be ready to adjust thyroid hormone because exogenous testosterone can reduce thyroid signaling.

Changing one signal (as in testosterone) causes multiple downstream signaling changes in other systems. As long as one is ready to make the adjustments to thyroid hormone signaling and other signaling systems with TRT (such as estrogen signaling, adrenal signaling, nervous system, immune system, metabolism, nutrition, etc.), then one can avoid some complications with TRT, such as anxiety, fatigue, hypertension, insomnia, body aches, etc.

Off the top of my head, there are several possible ways TRT can reduce thyroid hormone signaling, including the following:

1. Exogenous testosterone suppresses testicular testosterone production AND testicular thyroid releasing hormone (TRH) production. This reduces brain TSH production, lowering thyroid hormone production from the thyroid gland.

2. Exogenous testosterone may reduce liver production of thyroid binding globulin. This reduces the half-life of thyroid hormone. This leads to a reduction in available thyroid hormone.

3. Exogenous testosterone can lead to a simultaneous conversion of testosterone to estradiol. The increase in estradiol can increase liver production of thyroid binding globulin. This can lead to a reduction in free thyroid hormone levels (Free T3, Free T4). This then reduces thyroid signaling.

4. Exogenous HCG (human chorionic gonadotropin) not only increases testicular production of testosterone and sperm but also increases aromatase enzyme production. The increase in aromatase enzyme can then lead to an increase in estradiol production from testosterone. This (as noted above) can lead to a reduction in thyroid signaling.

5. Exogenous testosterone can suppress ACTH (adrenocorticotropic hormone) production from the brain. And it can directly suppress adrenal cortical activity, including cortisol production. This can then lead to an increase in norepinephrine production, then immune system inflammatory signaling. This can then shift thyroid metabolism so that T4 is converted to reverse T3 (the waste product pathway) instead of being converted to T3 (the active thyroid hormone). This can reduce both T4 levels and T3 levels, leading to a reduction in thyroid signaling.

When possible, I usually prefer to consider first optimizing thyroid signaling, adrenal function, immune system function, nervous system function, metabolism and nutrition, to allow a smoother transition to testosterone replacement therapy.

There are times when adding testosterone simultaneously while addressing the other systems is important to help break some positive feedback loops between systems that contribute to illness. For example, high insulin/insulin resistance/diabetes, obesity, inflammatory signaling, stress/norepinephrine signaling, and lower testosterone production can be involved in multiple positive feedback loops which can cause significant illness. Adding testosterone when it is low in such a person can help unravel the self-perpetuating signaling loops that keep a person ill.

Most often, men will have to increase the dose of thyroid hormone after starting TRT. I have yet to see a need to lower thyroid hormone in men who start TRT.

Off the top of my head, one possible mechanism by which testosterone can lead to an increase in thyroid hormone is if there is significant inflammatory cytokine signaling resulting in a shift of T4 metabolism to Reverse T3 rather than T3.

If exogenous testosterone helps reduce inflammatory cytokine signaling, it can then help reduce reverse T3, leading to an increase in T3 production from T4.

On the other hand, increased inflammatory signaling can also lead to an increase in sympathetic nervous system norepinephrine production, i.e. stress signaling. This may then increase deiodinase enzyme production, increasing T4 to T3
conversion.

If Testosterone reduces stress/norepinephrine signaling - and testosterone is usually a very calming signal unless a lot is transformed to estradiol - then the addition of exogenous testosterone would negate norepinephrine's increase in T3 production.

This can possibly negating the gain from the above anti-inflammatory effects of testosterone. This would lead to a wash in thyroid change from the addition of testosterone via these two mechanisms.

The sum of the above and other pathway influences on thyroid hormone would determine whether or not thyroid hormone increases or decreases with the addition of exogenous testosterone.

In my experience, usually, exogenous testosterone generally reduces thyroid hormone signaling. The population that I may see, however, may be different from that seen by other physicians.


· Question: Thanks for the detailed answer Dr. Mariano. And does higher and higher
estradiol bind more thyroid, making you more hypo?

I'm thinking if estradiol is brought down with DIM or arimidex, it would then
free up your bound thyroid, meaning you'd lower your thyroid dose. Yes? No

Answer:
It not that estradiol binds more thyroid hormone. Estradiol increases liver production of thyroid binding globulin which binds thyroid hormone, leaving less in the free form.

Reducing estradiol vis DIM or Arimidex works to a certain point, then worsens the situation.

Lowering estradiol would reduce thyroid binding globulin production. This increases free thyroid hormone. However, if thyroid binding globulin is reduced excessively, then the half-life of thyroid hormone is reduced. This results in an increased breakdown of thyroid hormone, leading to a reduction in total thyroid hormone.

Arimidex also has a limit in reducing estradiol. In some men, the body may compensate by increasing production of estradiol via alternative pathways when its production via the aromatase enzyme is reduced excessively. Thus there may be a ceiling in reducing estradiol after which the body uses other pathways to produce estrogen. Also other estrogens may be produced when estradiol is reduced excessively. One can't also reduce estradiol excessively before the liver compensates by increasing cholesterol production.

It is a matter of balance. Estrogens are monitored more closely by the brain than testosterone in determining production of the reproductive hormones."

I hope this gives you better understanding and more info to discuss with your Dr. Just my opinion: hCG will help you greatly, and get T3 if possible. When you do this, everything will shift around so don't hold yourself to any previous numbers.

Complete thread is here: http://www.swolesource.com/forum/mens-health-ancillary-medication/10-trt.html
 
Last edited:

Soilsample

New Member
Wow!
Thanks so much for all the information.
Obviously it is critical to get my Thyroid function on point so that I can get a better handle on the shbg and Estradiol.
I wish my doctor was up to speed on all this!
 
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