Found this old post by Dr. Marianco on a different forum and I thought it was interesting enough to share. Ideas? Personal experiences?
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The following is fairly speculative.
High levels of testosterone for long periods of time, can, I think, result in tolerance to the higher levels of dopamine in the brain. The initial almost euphoric feeling that initial TRT can eventually wane to a lesser level. When at hypogonadal levels for a long time, there may be suprasensitivity to dopamine that develops from the dopamine deficit of hypogonadism. This contributes to the high that results from TRT at the onset.
A problem for testosterone therapy is that there is no therapy that really mimics the daily fluctuations in testosterone production. Testosterone tends to be highest in the morning and fall gradually through the day. This means the dopamine levels in the brain will also follow a similar pattern. Testosterone treatment generally follows either a many day decay in level after a large peak (e.g. injections) or a very steady state level (e.g. transdermals or pellets).
Dopamine is one neurotransmitter that clearly can result in tolerance when present at high levels. Dopamine is a neurotransmitter that needs to vary in concentration hour by hour. On of its functions is to provide a feeling of reward on certain events. A reward cannot last forever, it has to have a finite life or one cannot differentiated it as a reward. TRT generally does not have the frequent fluctuations in dopamine level during the course of the day that natural testotserone production lends.
Dopamine sensitivity improves once a deficit is created.
Going off TRT periodically, which is done by ASIH, for example, would then allow dopamine sensitivity to return.
In a way, if dopamine insensitivity is an issue, then one other possible solution would be to have once a month injections such as a colleague of mine uses for her TRT clients. This causes a large peak and then a return to baseline hypogonadism before the next injection. Dopamine levels follow the testosterone curves - in this case having large changes in levels through the month.
The thought of giving a person their whole 4 week supply of testosterone in one injection gives me pause - for example out of concern for a roller coaster experience. The large dose of injection also is a concern. Problems with supraphysiologic levels of testosterone and other hormones at the onsent of treatment is a concern. From her experience, her technique works well for her clients. Perhaps this is one technique that maintains dopamine sensitivity since dopamine levels are constantly changing rather than remaining at the same high levels.
A third approach would be doing TRT in such a way as to avoid very high total testosterone levels - for example, going up to 400-500 ng/dl rather than 650-1000 ng/dl. This way, dopamine levels do not remain constantly high. There then is more headroom for the brain to produce more dopamine in the reward circuits of the brain on demend, without getting to high levels that promote tolerance. If sexual function is not optimal, then optimizing other hormonal systems such as thyroid and adrenal hormones may return sexual function at the lower target testosterone levels. As an example, with good thyroid and adrenal function, sex drive often persists to fairly low levels of testosterone.
---------------------------------------
The following is fairly speculative.
High levels of testosterone for long periods of time, can, I think, result in tolerance to the higher levels of dopamine in the brain. The initial almost euphoric feeling that initial TRT can eventually wane to a lesser level. When at hypogonadal levels for a long time, there may be suprasensitivity to dopamine that develops from the dopamine deficit of hypogonadism. This contributes to the high that results from TRT at the onset.
A problem for testosterone therapy is that there is no therapy that really mimics the daily fluctuations in testosterone production. Testosterone tends to be highest in the morning and fall gradually through the day. This means the dopamine levels in the brain will also follow a similar pattern. Testosterone treatment generally follows either a many day decay in level after a large peak (e.g. injections) or a very steady state level (e.g. transdermals or pellets).
Dopamine is one neurotransmitter that clearly can result in tolerance when present at high levels. Dopamine is a neurotransmitter that needs to vary in concentration hour by hour. On of its functions is to provide a feeling of reward on certain events. A reward cannot last forever, it has to have a finite life or one cannot differentiated it as a reward. TRT generally does not have the frequent fluctuations in dopamine level during the course of the day that natural testotserone production lends.
Dopamine sensitivity improves once a deficit is created.
Going off TRT periodically, which is done by ASIH, for example, would then allow dopamine sensitivity to return.
In a way, if dopamine insensitivity is an issue, then one other possible solution would be to have once a month injections such as a colleague of mine uses for her TRT clients. This causes a large peak and then a return to baseline hypogonadism before the next injection. Dopamine levels follow the testosterone curves - in this case having large changes in levels through the month.
The thought of giving a person their whole 4 week supply of testosterone in one injection gives me pause - for example out of concern for a roller coaster experience. The large dose of injection also is a concern. Problems with supraphysiologic levels of testosterone and other hormones at the onsent of treatment is a concern. From her experience, her technique works well for her clients. Perhaps this is one technique that maintains dopamine sensitivity since dopamine levels are constantly changing rather than remaining at the same high levels.
A third approach would be doing TRT in such a way as to avoid very high total testosterone levels - for example, going up to 400-500 ng/dl rather than 650-1000 ng/dl. This way, dopamine levels do not remain constantly high. There then is more headroom for the brain to produce more dopamine in the reward circuits of the brain on demend, without getting to high levels that promote tolerance. If sexual function is not optimal, then optimizing other hormonal systems such as thyroid and adrenal hormones may return sexual function at the lower target testosterone levels. As an example, with good thyroid and adrenal function, sex drive often persists to fairly low levels of testosterone.
