Men’s Sexual Health - Dr. Mohit Khera

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BigTex

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Men’s Sexual Health: why it matters, what can go wrong, and how to fix it

Mohit Khera interviewed by Peter Attia MD

Mohit Khera, M.D., M.B.A., M.P.H., Professor, is the Director of the Laboratory for Andrology Research at McNair Medical Institute, Baylor College of Medicine. He is also the Medical Director of the Executive Health Program at Baylor. Dr. Khera is a Board-certified urologist. As you will notice on Dr. Khera's web page, he has collaborated with Dr. Lipshultz here in Houston on research projects. Both of them are at Baylor College of Medicine in the medical center.


Very interesting video covering a wide range of men's sexual issues. About 2:08:00 he discusses testosterone replacement. He also says that giving 200 mgs IM every two weeks is the worst thing you can do because this causes a high rate of erythrocytosis. Then he discusses a better option of going twice a week. Later on Dr. Khera discusses what Dr. Crisler claimed back in the early 2000's that each of us should be treated individually because of the difference in androgen receptor sensitivity and that should be tested (2:11;00). He also mentions how blood ranges mean very little because of individuality. This completely explains why I was able to compete at a world class level with very minimal doses of testosterone than others.

 
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Defy Medical TRT clinic doctor

Men’s Sexual Health: why it matters, what can go wrong, and how to fix it

Mohit Khera interviewed by Peter Attia MD
mkhera
Mohit Khera, M.D., M.B.A., M.P.H., Professor, is the Director of the Laboratory for Andrology Research at McNair Medical Institute, Baylor College of Medicine. He is also the Medical Director of the Executive Health Program at Baylor. Dr. Khera is a Board-certified urologist. As you will notice on Dr. Khera's web page, he has collaborated with Dr. Lipshultz here in Houston on research projects. Both of them are at Baylor College of Medicine in the medical center.


Very interesting video covering a wide range of men's sexual issues. About 2:08:00 he discusses testosterone replacement. He also says that giving 200 mgs IM every two weeks is the worst thing you can do because this causes a high rate of erythrocytosis. Then he discusses a better option of going twice a week. Later on Dr. Khera discusses what Dr. Crisler claimed back in the early 2000's that each of us should be treated individually because of the difference in androgen receptor sensitivity and that should be tested (2:11;00). He also mentions how blood ranges mean very little because of individuality. This completely explains why I was able to compete at a world class level with very minimal doses of testosterone than others.

I’ve never asked this question on here, and my doctor had no clue. You and others (Nelson, Cataceous, Readalot, etc) seem to be knowledgeable about a lot of the research, so here goes. Has there been any study related to CAG repeat / androgen receptors that would indicate what general dosages / levels might be appropriate or “optimal” for a specific individual? I get the fact there are other factors at play that will influence this, but the only thing I ever found (didn’t save it) was a study done that showed a correlation between CAG repeat length and when an individuals hematocrit would go above 50 (if I am remembering right).
 
I’ve never asked this question on here, and my doctor had no clue. You and others (Nelson, Cataceous, Readalot, etc) seem to be knowledgeable about a lot of the research, so here goes. Has there been any study related to CAG repeat / androgen receptors that would indicate what general dosages / levels might be appropriate or “optimal” for a specific individual? I get the fact there are other factors at play that will influence this, but the only thing I ever found (didn’t save it) was a study done that showed a correlation between CAG repeat length and when an individuals hematocrit would go above 50 (if I am remembering right).
Not that I am aware of. General state of affairs as of 2015 in this review:


Testosterone and heart:


Clearly more is NOT always better.

CAG repeat and HDL / FMD:




A "general" correlation of cag repeat length length and quantitative therapeutic FT target for optimal health in HH would be nice but not aware of one. I assume the optimum FT target for optimal muscle hypertrophy is just a tad south of what will kill you over some specified time frame.

FFM:


See Fig. 1. Note the highest TT level measured.
 
Last edited by a moderator:
Not that I am aware of. General state of affairs as of 2015 in this review:


Testosterone and heart:


Clearly more is NOT always better.

CAG repeat and HDL / FMD:




A "general" correlation of cag repeat length length and quantitative therapeutic FT target for optimal health in HH would be nice but not aware of one. I assume the optimum FT target for optimal muscle hypertrophy is just a tad south of what will kill you over some specified time frame.

FFM:


See Fig. 1. Note the highest TT level measured.
I figured this was the case. You just hear so much about the CAG repeat and “receptor resistance” that it made sense to my simple mind there might be a way to target general levels based off of it.
 
Very interesting video covering a wide range of men's sexual issues. About 2:08:00 he discusses testosterone replacement. He also says that giving 200 mgs IM every two weeks is the worst thing you can do because this causes a high rate of erythrocytosis.
I try to hammer this home all the time and this sometimes falls on deaf ears. It’s one thing to start a man out on a protocol every 2-3 weeks, quite another when nothing else is working and options are limited.
 

Men’s Sexual Health: why it matters, what can go wrong, and how to fix it

Mohit Khera interviewed by Peter Attia MD

Mohit Khera, M.D., M.B.A., M.P.H., Professor, is the Director of the Laboratory for Andrology Research at McNair Medical Institute, Baylor College of Medicine. He is also the Medical Director of the Executive Health Program at Baylor. Dr. Khera is a Board-certified urologist. As you will notice on Dr. Khera's web page, he has collaborated with Dr. Lipshultz here in Houston on research projects. Both of them are at Baylor College of Medicine in the medical center.


Very interesting video covering a wide range of men's sexual issues. About 2:08:00 he discusses testosterone replacement. He also says that giving 200 mgs IM every two weeks is the worst thing you can do because this causes a high rate of erythrocytosis. Then he discusses a better option of going twice a week. Later on Dr. Khera discusses what Dr. Crisler claimed back in the early 2000's that each of us should be treated individually because of the difference in androgen receptor sensitivity and that should be tested (2:11;00). He also mentions how blood ranges mean very little because of individuality. This completely explains why I was able to compete at a world class level with very minimal doses of testosterone than others.


Hard to believe you missed this!

 

However, the relationship between CAG-RL and androgen receptor functioning has been shown to be tissue-specific (36, 37). While the effect of testosterone on adolescent depression is likely related to its effect on brain morphology and functioning (39), the relationship between CAG-RL and androgen receptor functioning in the central nervous system is not well-investigated. Perrin et al. (40) and Paus et al. (41) found a higher correlation between testosterone levels and white matter volume in male adolescents with fewer (≤22) CAG repeats than in those with longer (>23) CAG repeats. As myelination in the adolescent brain is considered an expression of structural maturation related to the effects of androgens (41), this may indicate that a lower number of CAG repeats is related to increased AR functioning in brain tissue. In adults, however, no correlation between CAG-RL and cortical AR mRNA, used as a surrogate parameter for androgen receptor functioning, was observed in a small-scale study of psychiatric patients (42). In summary, the effect of testosterone on androgen receptor activity in relation to the CAG-RL on brain function and its implications in mental health is insufficiently understood.

Limitations​

The exact relationship between testosterone and androgen receptor functioning is not fully understood, probably due to confounding factors, including non-genomic effects, potential epigenetic effects, and modifying genetic polymorphisms, which we were not able to account for in the present study. However, neither of these factors has been implicated in depression and its severity in humans so far.
 
Not that I am aware of. General state of affairs as of 2015 in this review:


Testosterone and heart:


Clearly more is NOT always better.

CAG repeat and HDL / FMD:




A "general" correlation of cag repeat length length and quantitative therapeutic FT target for optimal health in HH would be nice but not aware of one. I assume the optimum FT target for optimal muscle hypertrophy is just a tad south of what will kill you over some specified time frame.

FFM:


See Fig. 1. Note the highest TT level measured.
Still looking for the Natty 1500 ng/dl guy?
 
Still looking for the Natty 1500 ng/dl guy?
The truth is out there along with the 50 ng/dl FT stud!

Nice work here:


 
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I’ve never asked this question on here, and my doctor had no clue. You and others (Nelson, Cataceous, Readalot, etc) seem to be knowledgeable about a lot of the research, so here goes. Has there been any study related to CAG repeat / androgen receptors that would indicate what general dosages / levels might be appropriate or “optimal” for a specific individual? I get the fact there are other factors at play that will influence this, but the only thing I ever found (didn’t save it) was a study done that showed a correlation between CAG repeat length and when an individuals hematocrit would go above 50 (if I am remembering right).

No.

Would not get to caught up on this!

*A strictly defined threshold to TD is likely to be replaced by a continuum spanned by genetics as well as symptom specificity. In addition, the effects of externally applied testosterone can be markedly influenced by the CAG repeats and respective pharmacogenetic implications are likely to influence indications as well as modalities of testosterone treatment in hypogonadal men. Investigation of CAG repeat polymorphism in exon 1 of the androgen receptor gene may be useful in testosterone treatment regimens adjustment

*Genetic studies on AR could offer important insight into the most severe forms, as in complete AR resistance (ie, Morris Syndrome). However, in the mildest forms of resistance, such as those characterizing an expanded CAG repeat in exon 3 of AR, the hypothalamus-pituitary-testis axis resets itself because of a variation in the negative feedback, compensating for the diminished bioactivity of AR with a resulting minimal or null effect on phenotype.13 Hence, studying CAG repeat length is not useful in understanding the biology of androgen deficiency in the normal population, although it can be useful for pharmacogenetic purposes.

* Determination of the CAG polymorphism of the AR gene is not recommended for routine practice, but in the near future it can be used in particular for the selection of individual therapy for androgen deficiency


*The same applies to androgen receptor gene CAG repeat lengths >24 in the presence of symptoms and normal testosterone levels may be considered as a state of preclinical TD [93]

*
In humans, the AR gene comes in many forms, called alleles. The best-studied alleles are those involving a CAG repeat sequence that encodes a polyglutamine tract near the amino end of the androgen receptor. This CAG repeat has different lengths for different people. In humans, the number of AR CAG repeats ranges from as few as 9 to as many as 36, but population averages are typically between 17 and 24 (Chamberlain et al., 1994; Hsiao et al., 1999; Irvine et al., 2000; La Spada et al., 1991). Individuals with higher numbers of AR CAG repeats will normally have diminished testosterone action on cellular functioning, effectively making males with high AR CAG repeats less masculine regarding most sexually dimorphic traits when compared to males with fewer AR CAG repeats (Loehlin et al., 2004; Simanainen et al., 2011)

*
Based on a total sample of 57,826 males occupying 78 countries, the overall average number of AR CAG repeats was found to be 21.40. National averages ranged from 17.00 to 23.16. Five countries had averages in the 17.00s; they were Swaziland (17.00), Zambia (17.00), Sierra Leone (17.30), Nigeria (17.58), and Senegal (17.90). Five countries had averages of 23.00 or higher; they were Lithuania (23.00), Mongolia (23.00), Ireland (23.07), Thailand (23.10), and Romania (23.16).




 
I’ve never asked this question on here, and my doctor had no clue. You and others (Nelson, Cataceous, Readalot, etc) seem to be knowledgeable about a lot of the research, so here goes. Has there been any study related to CAG repeat / androgen receptors that would indicate what general dosages / levels might be appropriate or “optimal” for a specific individual? I get the fact there are other factors at play that will influence this, but the only thing I ever found (didn’t save it) was a study done that showed a correlation between CAG repeat length and when an individuals hematocrit would go above 50 (if I am remembering right).


 
Hard to believe you missed this!

WOW! I sure did. And you did a much better job presenting the whole lecture.
 
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