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  1. #1
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    Ever wonder where the "high" went after initially starting TRT?

    Dr. Mariano is a well respected Physician in the TRT vertical. I've read many of his papers and I consider him one of the best. The paper below describes why men get that initial "high" when they start a new TRT protocol after being low for a prolonged period of time. There are also other points of interest in this paper as well. This is very good read fellows...enjoy!
    ------------------------------------

    If a male is hypogonadal for an extended period of time, then the first exposure to testosterone repla***ent can be exhilarating. Then it eventually goes away.

    Here is a simplification of what may be happening:

    Testosterone increases dopamine signaling in the brain. Dopamine signaling promotes sex drive, attention, interest in activities, elevates mood, and is calming in effect since it also reduces norepinephrine signaling. Without testosterone, there may be an increase in dopamine receptor concentration due to the loss of dopamine signaling.

    Testosterone, itself, has a calming effect on the brain. It helps reduce norepinephrine signaling. Losing testosterone loses another of the control signals on norepinephrine production.

    The loss of testosterone production is also accompanied by a loss of testicular thyroid releasing hormone production. This results in a reduction in thyroid hormone production. This results in a reduction in metabolism and energy. The brain compensates by increasing norepinephrine production to increase energy. This increase in norepinephrine signaling can promote insomnia, irritability, anxiety. It also does not usually improve energy well.

    Over time, with aging, thyroid hormone production is reduced. This compounds the problem of thyroid loss accompanying testosterone production loss, including a further increase in norepinephrine signaling to compensate for the loss.

    Testosterone, overall, is an anti-inflammatory signal and helps govern adrenal function, preventing excessive production of cortisol. Without testosterone, under increased norepinephrine signaling levels, high cortisol production may occur - which may or may not cause problems.

    The elevated norepinephrine signaling may then be accompanied by pro-inflammatory cytokine signaling as the brain becomes chronically elevated by stress signaling/norepinephrine. Over time, this may then cause hypothalamic-pituitary-adrenal dysregulation with low cortisol production.

    Estradiol, functioning as an MAO, increases serotonin greater than norepinephrine. It promotes competitiveness, drive, sex drive, aggressiveness. Without testosterone, however, and the dopamine increase it promotes, Estradiol would tend to flatten sex drive and promote irritability and aggression, anger, instead. Unless testosterone production is very low, Estradiol can be maintained since so little in relationship to testosterone, is needed in men. The relative change in signaling strengths of each poses problems of excessive estrogen. This includes increased thyroid binding globulin and reduction of free thyroid hormone signals. Excess estrogen, by increasing serotonin excessively, may reduce sex drive.

    Norepinephrine is important for sexual function. It promotes the high and excitement that accompanies sex drive / libido. But in excess, it does not. It causes tension, stress, distress, anxiety, irritability, which lowers sex drive. To increase norepinephrine, the brain may reduce serotonin, GABA, then dopamine production - causing problems with deficiencies in serotonin, GABA and dopamine.

    Excessive norepinephrine production also causes insulin resistance. The increase in insulin production that results is pro-inflammatory. It also further reduces testosterone production. Insulin also promotes fat storage. The resulting increase in fat results in an increase in Leptin and other pro-inflammatory signals from fat cells.

    And so on and so on. These are some of the changes that permeate the system from the loss of testicular testosterone production. Some are added to by changes in the metabolism of the other cells which produce other signals such as thyroid hormone, through the process of aging or with nutritional problems or with genetic predisposition to other signaling or metabolic problems or through structural changes such as the loss of cells in the hippocampus and other brain structures.

    -----

    So what happens when testosterone is replaced?

    There is a reversal of some of the initial signaling problems.

    Because there is a larger number of dopamine receptors from the dopamine signaling deficit caused by the loss of testosterone, there is dopamine supersensitivity to the surge of dopamine signaling that accompanies the increase in testosterone with repla***ent. This can cause a high - with heightened sex drive, alertness. and an elevated mood.

    Testosterone would also free up thyroid hormone by reducing thyroid binding globulin, reversing estrogen's effects, improving function from this angle. This would improve energy

    Testosterone would then reduce excessive norepinephrine signaling, which as it comes more in normal physiologic strength, helps dopamine in providing a higher level of libido, sex drive, and an emotional high.

    The testosterone to estrogen ratio would improve, reducing effects of excess estrogen. Insulin signaling is reduced. The body becomes less in an inflammatory state.

    The person feels better, if not feels a high from the initial treatment with testosterone.

    ----

    Over time, however, with increased dopamine signaling, dopamine receptor production is reduced back to a normal amount. Dopamine, as the reward signal, the feel good signal, can't be elevated for a prolonged period of time excessively, without problems occurring. It no longer becomes a reward signal if it is elevated for a prolonged period of time. Tolerance, through receptor reduction, occurs.

    After the initial high, other problems also occur.

    Exogenous testosterone suppresses testicular thyroid releasing hormone production. This reduces thyroid hormone production, undoing the initial increase in free thyroid hormone that testosterone caused. If there is hypothyroidism in the first place, this exacerbates that problem.

    If there are other neurotransmitter, hormone, cytokine signaling problems or metabolic-nutritional problems outside of hypogonadism, these may complicate or undo what testosterone initially did.

    If the man aromatizes testosterone to estrogen excessively, problems with excessive estrogen occur. If aromatization is not enough, then problems with too little estrogen occur. In either case, sex drive is impaired.

    Thus, the hypogonadal man returns to Earth. And the initial high is lost.
    __________________
    -

    Romeo B. Mariano, MD, physician, psychiatrist

    Any information provided on www.definitivemind.com is for informational purposes only, is not medical advice, does not create a doctor/patient relationship or liability, is not exhaustive, does not cover all conditions or their treatment, and will change as knowledge progresses. Always seek the advice of your physician or other qualified health provider before undertaking any diet, exercise, supplement, medical, or other health program.

  2. #2
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    i guess thats why blasting once in a while is a good thing! thanks for the post GD!

  3. #3
    J DIESEL3 is offline Associate Member
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    Great post gd! And thanks for taking the time to pass this info. on J

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    I am hoping someone can elaborate on the ideas above with regards to my current situation.

    I am a 21 year old male that has been experiencing low libido among other things.

    I have been treated with antipsychotics for 12+ years for my tourettes. These medications are the root cause of my low libido.

    My recent bloodwork came back with a test level of 20. The secretary never told me the units. But setting average/optimal levels and ranges aside.. I think my low test is the cause of my current problems.. Low libido, anxiety, unpredictable energy/mood. My mood and energy can change quite easily. When I eat it changes too much than whats normal.

    Does anyone have any prior knowledge of people on antipsychotic medications who use hormonal therapy to counter balance their bodies?

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    Quote Originally Posted by Parsons51 View Post
    I am hoping someone can elaborate on the ideas above with regards to my current situation.

    I am a 21 year old male that has been experiencing low libido among other things.

    I have been treated with antipsychotics for 12+ years for my tourettes. These medications are the root cause of my low libido.

    My recent bloodwork came back with a test level of 20. The secretary never told me the units. But setting average/optimal levels and ranges aside.. I think my low test is the cause of my current problems.. Low libido, anxiety, unpredictable energy/mood. My mood and energy can change quite easily. When I eat it changes too much than whats normal.

    Does anyone have any prior knowledge of people on antipsychotic medications who use hormonal therapy to counter balance their bodies?
    You're hijacking this thread.

    Start a new one and post as much about your self as possible.

    See if you can get your blood work and post.

    Many hormonial imbalances can cause depression like symptoms.

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    I could only pronounce 2 words in that entire write up joke..........I read a similar article recently, not as in depth but basically stating that dopamine was responsible for the good feeling men got in that first little while after starting TRT. Interesting stuff for sure.

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    Vettester is offline Banned
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    Great information! Thanks for posting, GD.

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    As always gd, great info. Of course I had to read it a couple times! And btw, the hippocampus is my favorite place at the zoo!

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    ecdysone is offline Knowledgeable Member
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    Quote Originally Posted by kelkel View Post
    As always gd, great info. Of course I had to read it a couple times! And btw, the hippocampus is my favorite place at the zoo!
    Oh, God now I'll never be able to go there again, without this thought in my mind!!

    Anyway, thanks as always GD.

  10. #10
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    Quote Originally Posted by kelkel View Post
    As always gd, great info. Of course I had to read it a couple times! And btw, the hippocampus is my favorite place at the zoo!
    LMAO......that's OK Kel, I always thought globulin was something you dressed up as for halloween.

  11. #11
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    Am I reading into this wrong way , should We take A break from trt every once on a while ?

  12. #12
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    Quote Originally Posted by JAMIE07652 View Post
    Am I reading into this wrong way , should We take A break from trt every once on a while ?
    no! IMHO i suggest blasting once in a while, and maybe staking with deca or var!

  13. #13
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    Hey bass .. I guess I read into the post that you develop. A tolerance to test .

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    Quote Originally Posted by JAMIE07652 View Post
    Hey bass .. I guess I read into the post that you develop. A tolerance to test .
    Where did you read that?

    Hes not saying a man develops a tolerance or that it just stops working or becomes useless after time.

    He's stating that for the first few weeks a man who was severely hypogonadal for an extended period of time might experience euphoric "highs" from the return of good testosterone levels ...which makes sense when you think about it given the shitty suppressed condition they were in.

    Rather his point is that after a few weeks/months (different for each man) that "high" will most likely diminish and he wont feel that incredible feeling anymore but he will continue to experience the benefits of TRT as we all do.

    We hear this from men here all the time and I thought it was relevant for our discussion.

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    Yep^^^ I know many guys including myself have reported feeling a big difference within the first week or so which doesn't line up with what we know about the effects of testosterone but now we know it's the dopamine that's acting that quickly. Good info.

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    Quote Originally Posted by JD250 View Post
    LMAO......that's OK Kel, I always thought globulin was something you dressed up as for halloween.
    JD I'm still recovering from yesterdays piercing of my intellect with Ec's "agglutinate." Still trying to figure out how to use it in a sentence! Damn.

  17. #17
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    Good luck, I don't think I'll be able to use that one on the jobsite.

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    Quote Originally Posted by JD250 View Post
    Yep^^^ I know many guys including myself have reported feeling a big difference within the first week or so which doesn't line up with what we know about the effects of testosterone but now we know it's the dopamine that's acting that quickly. Good info.
    Correct JD; that's part of his point.

    There are other jems in this paper if you haven't caught them; but it's this statement that's worth every penny in reading and understanding:

    So what happens when testosterone is replaced?

    There is a reversal of some of the initial signaling problems.

    Because there is a larger number of dopamine receptors from the dopamine signaling deficit caused by the loss of testosterone , there is dopamine supersensitivity to the surge of dopamine signaling that accompanies the increase in testosterone with repla***ent. This can cause a high - with heightened sex drive, alertness. and an elevated mood.

    Testosterone would also free up thyroid hormone by reducing thyroid binding globulin, reversing estrogen's effects, improving function from this angle. This would improve energy

    Testosterone would then reduce excessive norepinephrine signaling, which as it comes more in normal physiologic strength, helps dopamine in providing a higher level of libido, sex drive, and an emotional high.

    The testosterone to estrogen ratio would improve, reducing effects of excess estrogen. Insulin signaling is reduced. The body becomes less in an inflammatory state.

    The person feels better, if not feels a high from the initial treatment with testosterone .

    WONDERFUL!

  19. #19
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    I also think part of the issue here is that like everything else - we get used to how we are feeling and therefore not as in tune. The good/great doesn't go away all together, we just get used to it to some extent imho.

    This is behind why some physicians do take their patients off for a period - not that it is a healthy decision, but they think once the patient crashes and feels like crap again the level of satisfaction with the treatment and therefore compliance with the protocol will improve. This methodology has made the circles in this field and we run into it every so often here.

  20. #20
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    Gdevine.. Like I said I might have read into the data a little too much . But , it seems to me that the data read ( between) the line a short break might not be a bad idea ? .. Idk

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    I don't remember getting a high/rush when starting TRT?

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    Quote Originally Posted by JAMIE07652 View Post
    Gdevine.. Like I said I might have read into the data a little too much . But , it seems to me that the data read ( between) the line a short break might not be a bad idea ? .. Idk
    IMO this "break" thing is just ridiculous.

    The body thrives on regularity and all this will do is send a man needlessly crashing and end up feeling like shit while throwing off all the other pathways at the same time...only to restart all over again...nonsense to me my friend.

    Think of this way; does a normal healthy man's system ever just shut down and restart as a normal biological processes??? Nope...

    So why a break?

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    Quote Originally Posted by Times Roman View Post
    I don't remember getting a high/rush when starting TRT?
    I do TR but I attribute more to the hCG protocol and not the Test.

  24. #24
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    Trust me , I will never stop taking my test and like u said going back to my shitty life , ever ! If anything , I'm thinking of a little. Blast cycle ! Thx for your input and what u say makes sence ..

  25. #25
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    I felt that "high" each time my levels of gel were increased, and as the article relates, that feeling went away after a period of time. I would talk about this to my endo and he would just sort of look at me, but never offered any explanation for what was happening. Thank you for showing us that information.

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