TRT Reference Range

Why is the reference range being lowered? I understand that we don’t know for sure if testosterone dropping in every generation is a bad thing for health outcomes, but should this be a cause for concern? If someone is getting symptoms of low T, but they are within the reference range, they might not get the prescription they need.

It’s probably just a different assay (test), which each have their own reference ranges. You could just ask the specific lab to get more insight.

That said, why are you so concerned about testosterone levels? And how do you know testosterone levels have gone down every generation? The tests have changed and there’s a lot of noise in that data. Finally, prescribing someone TRT or other medications to treat hypogonadism is a clinical decision based on symptoms, tests, and the entire clinical picture. It is highly unlikely that a change in laboratory references ranges is preventing folks from getting prescription T.

In general, people place FAR too much importance on testosterone levels.

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Dr. Austin Baraki seemed to confirm it in my old thread: Declining Testosterone - Medical Q/A with Drs. Feigenbaum & Baraki - Barbell Medicine Forum

I said:

Studies have shown a drop in testosterone in each generation. There are multiple factors that could be contributing to the decline (obesity, lack of exercise, stress, chemicals). Has anyone really nailed it down yet as the most likely culprit, or is it all of these things?

Then he replied:

We don’t really know. We also don’t definitively know whether it’s actually a problem.

I’m concerned about testosterone because I think our current high stress, sedentary lifestyle with rising obesity is contributing to this drop if T. I think Testosterone is important for assertive behavior, risk-taking, and male-female sexual equilibrium, so in short, I’m concerned that men are bigger cowards than their ancestors. Not everything has to be about health outcomes.

He did not confirm it was a thing or that it was a problem so, I’m not sure what you mean.

I’m concerned about testosterone because I think our current high stress, sedentary lifestyle with rising obesity is contributing to this drop if T. I think Testosterone is important for assertive behavior, risk-taking, and male-female sexual equilibrium, so in short, I’m concerned that men are bigger cowards than their ancestors. Not everything has to be about health outcomes.

I don’t think there is a drop in T and I think you’re placing far too much importance on T levels within the normal range based on present evidence.

From my understanding (and correct me if I’m wrong), you DON’T believe that there is a drop in T in our generation compared to previous generations, and Dr. Baraki thinks there IS a drop in T and we don’t know why? So there is disagreement between the two of you?

I’m concerned about testosterone because I think our current high stress, sedentary lifestyle with rising obesity is contributing to this drop if T.

I agree that a high-stress lifestyle, obesity/metabolic disease, poor sleep, and many other lifestyle factors can contribute to clinical hypogonadism. We discuss this regularly.

I think Testosterone is important for assertive behavior, risk-taking, and male-female sexual equilibrium

We are not disputing established biological effects of testosterone.

I’m concerned that men are bigger cowards than their ancestors. Not everything has to be about health outcomes.

You are free to be concerned about this. We are not.

I literally said “we don’t know”. I don’t know whether there is a true “generational drop”, nor do I care about this outside of a individual person/patient-level context. If someone presents with signs or symptoms of hypogonadism I will evaluate them accordingly, since that is my job as a physician. If not, I am not concerned about it, or about “men being bigger cowards than their ancestors”.

Ah, I thought you meant we don’t know what is contributing to the drop, and whether or not it’s a problem.

Do you think it’s possible we are underdiagnosing people because it’s never brought up by the patient or the physician? I read that researchers say only 5% of those with hypogonadism seek treatment.

It’s possible to underdiagnose any condition where an individual with a condition does not seek care, if they seek care and do not report symptoms, or if the physician does not consider a condition as a potential diagnosis. It’s also possible to overdiagnose conditions for a variety of reasons I’ve discussed in our podcast (and the Sigma Nutrition podcast) episode on screening and testing.

A final word: In another thread you said:

There is no such thing as a generalizable “optimal” testosterone level. There is a rather broad physiologically normal range, and variation within this range tends to not be particularly meaningful or predictive of better/worse outcomes.

I understand you are saying that if you’re not hypogonadal, then any increase in test within that range won’t have any additional health outcomes (better or worse). Does this also apply to older men, or could we eventually find out that TRT may increase their quality of life, regardless of the fact that it’s normal for T to decline in aging men?

Also, you do agree that testosterone can influence behavior, so I was wondering if indeed optimizing testosterone in a person who is NOT hypogonadal could still contribute to a positive outlook, less stress, and higher self-esteem through T’s potential behavioral changes and body recomposition? I understand that too much T can increase the risk of health problems, so I wonder if finding a “sweet spot” would actually be beneficial on an INDIVIDUAL basis, rather than a generalizable “optimal” dose.

Thanks for your time, and I always appreciate the work you do.

Based on current evidence, for individuals who are not clinically hypogonadal (i.e., who do not have signs and/or symptoms of hypogonadism, plus a low total testosterone level when measured properly), we do not have clear evidence of health benefit for variations in blood testosterone concentrations within normal ranges. I cannot predict what we “could eventually find out” in the future.

If you expand your scope to include older men with unequivocally low blood levels, you can check out the “Testosterone Trials”, a series of 7 RCTs in men in their 70s treated and evaluated for various outcomes, with some interesting results.

Once again: there is no definition of “optimal” testosterone levels in someone who is not hypogonadal.

We addressed this in the last thread you linked. Physiologic effects of testosterone involve more than just a blood concentration, but also involves things like individual differences in androgen receptor expression and sensitivity – which may render differences in blood levels irrelevant and/or un-interpretable. Furthermore, measurement and interpretation of blood levels is itself fraught with error due to things like circadian rhythmicity, protein binding, lab/assay error ranges, and others. It turns out that endocrinology is more complicated than ordering a test and treating a number.

If I suspect someone may have hypogonadism, I am happy to evaluate and treat it (and frequently do). But it is silly to hold such a myopic focus on a snapshot blood level, and even sillier to reduce major aspects of human behavior, social interaction, and mental health down to such a number.

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Are people with higher AR concentrations and sensitivity healthier because they use testosterone more efficiently? This takes me back to the study you once linked to about how recovery is better for people who work out while on TRT and then come off. This interests me…

I’m not aware of any evidence on this with respect to health.

It’s an even more complex question because AR concentrations will vary by tissue site. Someone who has a higher AR concentration in hypothalamic / pituitary feedback sites would then have naturally lower blood testosterone levels, since they “need” less to get the same effect - and this lower blood level will be physiologically appropriate and of no health consequence. Endocrinology is complex.