REASONS FOR THE TESTOSTERONE HIGH

[atrollappears]

I've created another thread to show the effects of Testosterone exogenous application on hypogonadal subjects:

If a male is hypogonadal for an extended period of time, then the first exposure to testosterone replacement 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.

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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 replacement. 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.

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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.

The situation isn't totally negative.

As long as one attempts to optimize the entire system, then testosterone will generally have a good effect on libido to one's satisfaction.

If a good amount of testosterone in men - 650 ng/dl - is present and problems remain, then there is more work to be done on the rest of the system to improve function.

Generally, it is very difficult to maintain the testosterone high and very high level of libido as seen in the teenage years. Enough dopamine neurons, for example, may have died off as a result of agin, to prevent full return to a high state.

It is highly important to optimize nutrition to improve function. This may entail more meats and saturated fats in the diet, for example.

Keeping testosterone at fairly flat levels may help, since peaks of testosterone may result in reduction in dopamine receptors and an increase in dopamine reuptake transporters. Keeping testosterone at flat levels may require more frequent dosing. The extreme flat dosing is achieved via testosterone pellet placement.

Once as many factors are addressed, one can then look to see if growth hormone replacement is needed. This may further increase libido in some people.

Libido is effected by the neurotransmitters.

Testosterone + dopamine (w/ proper estrogen) = libido

Prolactin = no libido

Nitric oxide + acetylcholine (w/ proper estrogen) = genital arousal

Norepinephrine (in the spine & genitals) = + orgasm

Serotonin (in the spine & genitals) = - orgasm

This is a simple concept w/ a lot of complexity. For example a lack of B vitamins (B5 for example) & choline can reduce neurotransmitter activity. So dietary & absorption considerations come into play. Often rather then addressing all these components, adding a hormone like testosterone may over time add positively to all the components not just testosterone itself. For example w/ testosterone there may be more enzymatic activity that promotes the retainment of needed factors or gets rid of inhibitory factors. There is a lot of interplay.

Addressing the fatigue is the most important part. The libido should follow.

 

[GyzzBrah]

Daz do you recon it could also be possible that the ''high'' is always present throught trt, but the person simply gets used to it over time, and the actuall physical changes to dopamine, seretonin etc stay the same?

[atrollappears]

Daz do you recon it could also be possible that the ''high'' is always present throught trt, but the person simply gets used to it over time, and the actuall physical changes to dopamine, seretonin etc stay the same?

Nope..!!    Otherwise you would feel it...

Its called down-regulation, or de-sensitization.. Too much of anything however small the amount above normal levels your body will get used to it and take appropriate action...

Homoeostasis kinda sucks..

[justhell]

Hey Daz,whats your thoughts on adding T3 after or during pct after comimg off 18 months of cruise/blast?

[Dinahlady]

.

[Dinahlady]

As well as what you've mentioned, there's a lot of research into amygdala functioning + test. Amygdala is closely related to mood.  Theres even quite a bit of research in to it with females.

The difficulty with these studies is that mood is subjective, but brain function isn't. Often the studies objectively show increased neurotransmission (e.g. of dopamine or in the amygdala) but they can't seem to get data and "prove" that this comes along with increased mood effects. The experimental methods to determine mood are subjective and don't often come out with any correlation, or they come out with one that isn't statistically significant. 

Good topic though. 

[atrollappears]

Hey Daz,whats your thoughts on adding T3 after or during pct after comimg off 18 months of cruise/blast?

T-3 can be catabolic, and is recommended with AAS to avoid muscle loss.... Not the best thing when your HPTA is all over the place... 

18 months thats a long time, what PCT protocol are you employing..?

[justhell]

Yeah Daz its been a while ,more blast than cruise aswell,time to give the body a break.

Because i was running tren e for a while at 500mg pw,i know its gonna be active for a few weeks after last shot.and the sweats keep on coming haha (gotta love them)

10 days after last shot i started clomid 50mg ed,il keep that going for 4 weeks

Been thinking bout starting nolvadex tomorrow? Which Is 2 weeks after starting clomid.

Gonna run 20mg nolvadex ed for 4 weeks then a bit of adex on my last 5 days of pct.