OK, what I am about to write is a fairly dense post:
Attempting to raise SHBG to treat sexual dysfunction/hypogonadal symptoms is irrational in my view. My view, unlike the contrary view that low SHBG can cause hypogonadal symptoms, is at least supported by some emergent published evidence and a logic that I will try to explain clearly:
While there is
valid evidence that
high SHBG & low free T (low free androgen index; low FAI) is associated with hypogonadal symptoms; there is no evidence (that has been subjected to rigorous research & statistical methods) that low SHBG is associated with hypogonadal symptoms that I have seen.
While I certainly see anecdotes ( including from those whose anecdotes I assign more than a scintilla of value like
@GreenAmine ) and informal hypothesizing about low SHBG & hypogonadal symptoms, the more likely (in my estimation) modulating influence involves megalin (SHBG promoter gene) and nongenomic, at least in part, action (e.g., at Sertoli cell surfaces).
I consider it unlikely that lowering SHBG causally induces hypogonadal symptoms considering the rapid onset of these symptoms, and what we know about the SHBG promoter gene - megalin (though admittedly, what we know is markedly limited).
Rather than low SHBG inducing hypogonadal symptoms
per se, there may be an influence on spermatogenesis & sexual function mediated by SHBG-androgen (i.e., different androgens with SHBG binding affinity form a different complex with SHBG; e.g., methenolone-SHBG or boldenone-SHBG) complexes that are taken up into Sertoli cells (testicular cells that are involved in spermatogenesis). We have evidence of megalin's influence on secondary sex characteristics & SHBG-T complexes being taken up into Sertoli cells via megalin receptors, and
criticially, that have been shown to influence PKA activity by nongenomic mechanisms (e.g., via cell-surface receptors).
The rapidity of onset (after, e.g., front-loading EQ, Primo) in hypogonadal symptoms suggests that, perhaps, there is an interaction between AR & SHBG at the cell surface (without uptake therein), increasing PKA activity via megalin receptor. There is evidence that the intracellular interaction of the AR-SHBG complex with megalin receptor may increase PKA activity and this could influence AR-mediated transcription by altering AR phosphorylation and that of its coactivators.
Nobody has ascertained at what SHBG concentration problems arise (sexual dysfunction & hypogonadal symptoms) - but I suspect that it is
extremely low.
Conclusion:
Rather than low SHBG inducing hypogonadal symptoms
per se, perhaps it is more likely that the particular effects of different AR-SHBG complexes in and at Sertoli cells (and perhaps, speculatively, via other cell surface receptors, e.g., in the hypothalamo-pituitary axis), differentially influence hypogonadal symptoms.
My view is supported by the frequent observation of the onset of hypogonadal symptoms being a
rapid (i.e., nongenomic) effect, e.g., the onset of these symptoms after a Primo or EQ bolus (especially front-loaded) is consistently reported as rapid (too rapid to be mediated exclusively by genomic action; reduction to SHBG, etc.)
