It took me 2 years to master these interaction below. I am always continuing to learn more.
1. Testosterone can increase dopamine levels in the brain.
2. Increasing dopamine levels may reduce serotonin levels - since their production is inversely related.
3. Serotonin help reduce perceived stress and helps reduce anxiety symptoms.
4. Reduction in serotonin level may increase the likelihood of perceived stress and anxiety.
5. Increased perceived stress and anxiety may cause the brain to increase Adrenocorticotropic Hormone (ACTH) release.
6. The ACTH signal is received by the adrenal glands, which in turn starts the stress response (including increasing cortisol, norepinephrine, epinephrine production, among the 50 hormones produced by the adrenals).
7. Increased perceived stress may activate the sympathetic nervous system, which then increases output of norepinephrine from the brain as part of the fight-or-flight reaction.
8. Increased testosterone may also lead to aromatization of testosterone to estradiol/estrone (estrogens).
9. Estrogens have multiple effects including behavioral effects such as increasing anxiety, irritability, hyperactivity and aggression.
10. Estrogen increases the expression of receptors and other associated proteins for neurotransmitters including serotonin, norepinephrine, and dopamine.
11. Reduction in serotonin level from increased dopamine levels may affect thyroid hormone conversion in the liver from T4 to T3 via the cytochrome P450 2D6 enzyme.
12. Reduction in active thyroid hormone may destabilize mood - perhaps contribute to anxiety, hyperactivity
13. Estrogen itself may compete with thyroid hormone at the thyroid hormone receptor site - creating a virtual hypothyroid state - perhaps also contributing to anxiety - despite normal thyroid hormone levels.
14. Remeron's mechanism of action includes increasing serotonin release, increasing norepinephrine release (at higher doses), and by blocking histamine receptors (accounting for sleepiness and weight gain at lower doses).
15. Remeron, in my experience, does not work well to reduce anxiety.
16. Increased norepinephrine levels from Remeron makes a person more likely to have anxiety when norepinephrine is further increased and serotonin decreased - from other causes - such as those written above.
17. The higher the dose of Remeron, the higher the increase in norepinephrine, the higher the likelihood of anxiety.
18. One of testosterone's functions is to reduce stress by reducing ACTH production from the brain and by directly reducing adrenal gland hormone production (i.e. reducing cortisol production).
19. Should the adrenal gland, from long term exposure to anabolic steriods, become tolerant to the effects of testosterone, testosterone may not be able to reduce stress and anxiety.
20. Adrenal insufficiency may occur from long term anabolic steriod use - where the adrenals cannot make adequate cortisol and other hormones as needed when stressed to handle stress.
21. Adrenal insufficiency/fatigue results in intolerance of stress, fatigue, chronic sleepiness, irritability, anxiety.
22. Tolerance to testosterone's effects in the brain may occur with long term anabolic steriod use.
23. Testosterone usually has a calming effect. This may not occur if tolerance occurs to testosterone.
24. With adrenal fatigue, progesterone levels are reduced.
25. Progesterone is being shunted to create more cortisol in adrenal fatigue.
26. Progesterone has a mood stabilizing, calming, antidepressant, sleep-promoting effects through several mechanisms of action.
27. Progesterone increases seroronin, norepinephrine, GABA, dopamine activity in the brain. Progesterone blocks NMDA Glutamate receptors. Progesterone promotes myelination of nerves to improve signal transmission. Progesterone increases Estrogen receptor sensitivity. Progesterone promotes thyroid hormone activity.
28. Low progesterone levels may lead to increased anxiety, insomnia, tension, and mood instability.
29. Low testosterone levels and high cortisol levels (as a result), may lead to insulin resistance.
30. Insulin resistance not only predisposes one to diabetes, it impairs neuron signal transmission, and directly reduces testosterone production.
31. Insulin resistance may increase the likelihood of mood instability, anxiety, depression.
32. A serotonin-reuptake inhibitor (a group of medications with many members) increases serotonin more specifically than other effects.
33. Increasing serotonin has a calming effect.
33. Increasing serotonin excessively, however, causes a reduction in dopamine production.
34. Excessive serotonin, and subsequent reduction in dopamine causes a motor movement disorder called akathisia.
35. Akathisia has symptoms including anxiety, panic attacks, insomnia, irritability, restlessness, hyperactivity, agitation (to the point of suicide attempts by some people).
36. When attempting to balance or optimize the effects of one hormone/neurotransmitter, one may have to balance or optmize the effects of others to obtain the desired state. Testosterone, Estrogen, Progesterone, Cortisol, Insulin, Thyroid Hormone, Dihydrotestosterone, the metabolites of progesterone, Norepinephrine, Epinephrine, Serotonin, Dopamine, GABA (gamma amino butyric acid), Glutamate, Histamine, etc. are highly interlinked in their effects - with the endpoint of allowing a person to maintain balance between health and the stress the person faces.
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