Well, shit. I guess I will just be looking for “success” stories of people who have LOW T, yet don’t look and feel like crap. because I’m having second thoughts on taking any form of T after reading this:
Reasons why testosterone replacement can increase anxiety and impulsiveness
Testosterone (or one of its metabolites) can decrease the sensitivity of the adrenal glands, meaning that for a given amount of ACTH (a hormone excreted by the pituitary gland in the brain) less adrenal hormones are produced, including cortisol. If the person’s basal stress state can be characterised as one with elevated stress hormones (Norepinephrine, Epinephrine) with a blunted cortisol response, then testosterone supplementation can interfere with the body’s stress negative feedback mechanism and result in increased stress hormones, especially the inhibition of stress hormone release via the sympathetic nervous system. Cortisol is produced by the adrenal glands (as well as other stress hormones) in response to ACTH. The increase in cortisol is fed back to the brain where it reduces the stress response by reducing the production of ACTH and via the nerve sympathetic nervous system to the adrenal glands.
Testosterone replacement can blunt the cortisol response to ACTH. Without sufficient cortisol the ability of serotonin to inhibit glutamatergic activity in the lateral amygdala is greatly reduced. The amygdale is an area of the brain that is implicated in “flight or fight” stress response, in other words anxiety and panic attacks.
Some of the metabolites of testosterone (namely estradiol and estrone) can increase the binding of cortisol via cortosol-binding globulin, making it unavailable for use as free-cortisol. Again, this can interfere with the negative feedback mechanisms required to suppress the stress response.
Some of the metabolites of testosterone (namely estradiol via aromatisation of testosterone) can inhibit the deiodinase enzyme pathway in the central nervous system and peripheral organ (the liver), reducing the availability of T3 via the inhibition of the conversion of thyroid hormone T4 to T3. The reduction of active T3 can result in the down-regulation of the serotonin 5HT receptors in the brain, increasing the sensitivity of the body’s stress system.
One of the metabolites of testosterone (namely estradiol via aromatisation of testosterone) can increase glutamatergic activity in the brain. Too much activity and we perceive that as stress, anxiety and panic.
One of the metabolites of testosterone (namely estradiol via aromatisation of testosterone) modulates the serotonin 5HT system in a complex way. Initially it seems to up-regulate the 5HT system (good for lowering stress and anxiety), then a little later seems to down-regulate the 5HT system (bad for anxiety).
Men with more body fat are more likely to aromatise more testosterone to estrogen metabolites and experience the problems above. The aromatise enzyme is contained within fat cells.
Men with existing HPA abnormalities - blunted cortisol response to ACTH challenge, flat diurnal salivary cortisol profile, sub-clinical Addison’s disease, adrenal insufficiency, chronic fatigue syndrome or any sub-clinical hypocortisolism condition are more likely to respond to testosterone supplementation negatively.
Men with existing thyroid abnormalities â?? either clinical or sub-clinical hypothyroid or hyperthyroid are more likely to respond to testosterone supplementation negatively.
To address these issued a full workup is required in the following order:
Adrenal profile evaluation
Thyroid profile evaluation
Androgen profile evaluation
Growth hormone profile evaluation
Neurochemical profile evaluation
Each of these needs to be evaluated in the above order and treated in this order."
OOOK, but I’ve had extensive workups. All point to something “wrong”, but doctors can’t/won’t treat it. e.g. my last endo said I have reactive post pradinal hypoglycemia AND pseudopheochromocytoma. But didn’t offer a way to fix either.