Yes, if the enzymes that are involved in the final metabolism of hormones are increased it will lead to a novel form of hypogonadism.
In fact it would lead to an incurable form of hypogonadism. In this thread I quote research papers showing that even when rats are being injected with test cyp it has no effect on their prostates if hormone metabolism is increased.
Hormone/xenobiotic metabolism includes: Phase 1, the deactivation of hormones by CYP450 3A4 and/or Phase 2, during which hormones are deactivated & made water soluble for excretion. The most important of these two in this theory is Phase 2 metabolism, where hormones are conjugated (combined) with sulfide or glucurinide. (and it is the sulfotransferase enzyme that is enhanced when metabolism is increased.)
This is true for various reasons:
1.Sulfunated hormones do not bind to SHBG - this may alter the true bioavailablity of testoterone because the Sulfunated hormones are unable to bind to the androgen receptor. (only a small amount of testosterone is normally conjugated at any on time)
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Sulfunated testosterone is a better substrate for 5aR than unconjugated testosterone (it is therefore a natural anti-androgen) (see; Hydrogenation of Testosterone Sulfate by the Δ4-3-Ketosteroid Reductase of Rat Liver Microsomes)
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The product of 5aR + Testosterone sulfate is DHT sulfate. The product of DHT Sulfate + 3aHSD will be 3aDiolS(ulfate) - not 3aDiolG(lurunide). Leading to low 3aDiolG.
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The literature suggests that the increased sulfotransferase enzyme is present not only in the liver but also in sex hormone dependent tissue.
Phase 1 metabolism is less important, but it can at least also lead to decreased bioavailabilty of thyroid hormones. (so this mechanism could cause ‘brain fog’ etc).
There are problems with this theory.
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If the bioavailabilty of testosterone was substantially decreased, more people would notice muscle loss. However, testosterone sulfate is a better 5aR substrate than normal testosterone and also the sulfotransferase enzyme may be increased in sex-hormone dependent tissue, so that might explain that.
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I have no clue why finasteride should make this happen, unless for some reason the body is still stuck in an enhanced form of metabolism after quitting. (Xenobiotics, like finasteride - and sex hormones are acted upon by Phase 1 and Phase 2 metabolism in exactly the same way).
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DHT levels are normal. For this theory to work either DHT sulfate must be detected as normal DHT or both DHT and DHT sulfate are present at the same time.
Since enhanced metabolism definately can cause the symptoms it is a good theory and worth testing for. (in reality it is the only theory that adequatley explains the stranger symptoms and the ‘crash’). It also explains why NO ONE is growing gynocemastia - estrogens are deactivated in exactly the same way.
I am not stuck on this one theory and I am now investigating 5aR’s role in the CNS.
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