Study suggests WHY low SHBG is actually bad despite T levels

[Ausguy222]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/

Says it all, really.

In this study we have demonstrated that in the absence of SHBG large amounts of Te rapidly enter the cell where they are inactivated by conjugation to glucuronic acid and effluxed. In the presence of SHBG however, while there is reduced Te uptake, glucuronidation and efflux of Te are also reduced and the effects of Te on androgen responsive genes are enhanced. This in vitro study of the role of SHBG may have significant clinical relevance, and as such, the assessment of androgen deficiency in vivo should simply rely not only on measurements of total Te alone but also on the evaluation of serum SHBG levels.

These findings clearly demonstrate that SHBG plays an important regulatory and intracellular role to modify Te metabolism and function and to promote cell growth. These observations will need to be confirmed in other androgen sensitive tissues. If a consistent effect is demonstrated, it will significantly change our current understanding of the role of SHBG in health and disease.

[Cataceous]

James also recently alluded to this or related studies.

Per the study, without SHBG present, "intracellular testosterone is rapidly glucuronidated and effluxed."   

IOW, "fast metabolizers" and "hyperextreters" are doing both at the INTRACELLULAR level in addition to the serum level.

[Ausguy222]

Interesting, I did search to try and find a prior link.

Certainly makes sense why notorious SHBG lowering compounds - such as Proviron and Drostanalone, can TAKE AWAY libido when overdone - certainly has happened to me, a low SHBG guy.

[Cataceous]

He didn't post a link, so I'm glad you did...

[Dr Justin Saya, MD]

Certainly fits when you follow the clues of how low SHBG guys generally respond to TRT (including the impact of frequency of administration).

[Ausguy222]

Certainly,

I wonder where the cut off line is in real practice? And whether other hormones permeate differences or if it is solely Test based.

[PeakT]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/

Says it all, really.

In this study we have demonstrated that in the absence of SHBG large amounts of Te rapidly enter the cell where they are inactivated by conjugation to glucuronic acid and effluxed. In the presence of SHBG however, while there is reduced Te uptake, glucuronidation and efflux of Te are also reduced and the effects of Te on androgen responsive genes are enhanced. This in vitro study of the role of SHBG may have significant clinical relevance, and as such, the assessment of androgen deficiency in vivo should simply rely not only on measurements of total Te alone but also on the evaluation of serum SHBG levels.

These findings clearly demonstrate that SHBG plays an important regulatory and intracellular role to modify Te metabolism and function and to promote cell growth. These observations will need to be confirmed in other androgen sensitive tissues. If a consistent effect is demonstrated, it will significantly change our current understanding of the role of SHBG in health and disease.

Just read this:  super interesting find.  Thx.