“High-Normal T”

[JRos895]

For so long we used to believe that “low-normal” estrogen was optimal in men, which seemed to based off of cartoonish representations of hormones rather than scientific evidence. Of course, we now know that low-normal estrogen is not only not optimal, but potentially unhealthy.

Will we soon come to learn that “high-normal” testosterone is potentially unhealthy, or at the very least, not optimal? I hear so many posters and doctors claim that “high-normal” testosterone is optimal, but this seems to have no research backing this and seems based off of a cartoonish representation of testosterone much like the old posture towards estrogen.

In my own experience (for whatever it’s worth) my libido, energy, well-being, and even athletic performance was best when my testosterone is simply “mid-normal”. The only facet that was better with high testosterone was better muscle growth.

@Cataceous @readalot Would love to hear your thoughts on this.

 

[Belekas]

For so long we used to believe that “low-normal” estrogen was optimal in men, which seemed to based off of cartoonish representations of hormones rather than scientific evidence. Of course, we now know that low-normal estrogen is not only not optimal, but potentially unhealthy.

Will we soon come to learn that “high-normal” testosterone is potentially unhealthy, or at the very least, not optimal? I hear so many posters and doctors claim that “high-normal” testosterone is optimal, but this seems to have no research backing this and seems based off of a cartoonish representation of testosterone much like the old posture towards estrogen.

In my own experience (for whatever it’s worth) my libido, energy, well-being, and even athletic performance was best when my testosterone is simply “mid-normal”. The only facet that was better with high testosterone was better muscle growth.

@Cataceous @readalot Would love to hear your thoughts on this.

I'm not that experienced as any of your mentioned guys but have been in the field for close to 20 years. From my own personal experience I'm leaning towards the same outcome as you mentioned here. On 100mg/week I'm right at the top of the range with my TT and cFT. I feel good, libido is ok, sleep is great, body composition changing in regards to my diet manipulation and everything seems to click. With the way my body is responding I def don't need more and even likely that less will be even better. So something to try in the future. Before starting TRT i had barely in range cFT and still felt good, libido was ok, erection good, etc, so wanted just to see if raising my FT would help anything besides athletic body composition which at this point seems like the biggest benefit together with more masculinity and maybe decisivness, if I can say so. Not sure about actual cognitive function performace as I'm still in process of gathering data and figuring it out.

 

[Cataceous]

...
Will we soon come to learn that “high-normal” testosterone is potentially unhealthy, or at the very least, not optimal? ...

@Cataceous @readalot Would love to hear your thoughts on this.

I've been arguing in favor of this viewpoint for some time now. We know that testosterone interacts with a multitude of other hormones, so it's not a stretch to suggest that an excess of testosterone relative to what's appropriate for an individual is going to cause problems. I've also argued that average testosterone levels are already optimized by evolution, selected to give the best chance of reproductive success, which I further argue is a decent marker for overall success in life. There's a possible counter-argument, which says that conditions have changed for recent generations, with less exercise, poor diets, obesity and endocrine-disrupting chemicals all contributing to emasculation. Nonetheless, I'd say this is an argument for being a little above average, not for putting everyone in the top 10%. And there are still going to be some men who do better with below-average levels. This should be acknowledged, and the low-and-slow approach should be applied to TRT as a matter of course.

 

[BigTex]

I think this statement from Defy kind of sums it up:

What are Normal Testosterone Ranges?​

LabCorp defines the normal range for Testosterone in men as: 264 ng/dL to 916 ng/dL.

Does that mean if you have a Testosterone level of 265 ng/dL, you’re in the “normal” range and can’t experience low Testosterone symptoms?

Not exactly. There are a few issues with defined ranges like this.

For one, that range is very wide, and a man who has a level of 265 ng/dL will likely not have the same experience as a man with a level of 800 ng/dL. Yet they would both be considered normal if we only use this Testosterone scale for diagnosis. In addition, every man’s optimal range is unique to him and can depend on many physiological factors.

If you only look at lab-work and a predefined normal Testosterone range, you’re missing half of the story.

That’s why it’s important to incorporate symptomology into diagnosis.

Assessing symptoms helps providers understand how Testosterone levels are actually affecting the patient, which can identify whether there’s a Testosterone deficiency – even if the patient would be considered “normal” based on this range.

There’s also a difference between “normal” and “optimal.” At Defy Medical, we want to keep you in a healthy, normal range, but we also want you to be at an optimal range for your body, which might be higher than what a primary care or non-specialty doctor would have you reach.

Based on treating roughly 15,000 patients, we’ve found that the average optimal range for men is around 800 ng/dL – 950ng/dl. However, this isn’t a hard and fast rule, and it depends how the patient is responding to Testosterone replacement therapy.

That’s why we don’t offer cookie-cutter programs – because each patient has specific needs and unique optimal ranges.

Seems that is a typical issue here where treating the numbers is more important than treating the symptoms. Optimal should be at the point in which you no longer experience symptoms and that is, as in most things with the human body, very independent.

 

[JRos895]

I think this statement from Defy kind of sums it up:

What are Normal Testosterone Ranges?​

LabCorp defines the normal range for Testosterone in men as: 264 ng/dL to 916 ng/dL.

Does that mean if you have a Testosterone level of 265 ng/dL, you’re in the “normal” range and can’t experience low Testosterone symptoms?

Not exactly. There are a few issues with defined ranges like this.

For one, that range is very wide, and a man who has a level of 265 ng/dL will likely not have the same experience as a man with a level of 800 ng/dL. Yet they would both be considered normal if we only use this Testosterone scale for diagnosis. In addition, every man’s optimal range is unique to him and can depend on many physiological factors.

If you only look at lab-work and a predefined normal Testosterone range, you’re missing half of the story.

That’s why it’s important to incorporate symptomology into diagnosis.

Assessing symptoms helps providers understand how Testosterone levels are actually affecting the patient, which can identify whether there’s a Testosterone deficiency – even if the patient would be considered “normal” based on this range.

There’s also a difference between “normal” and “optimal.” At Defy Medical, we want to keep you in a healthy, normal range, but we also want you to be at an optimal range for your body, which might be higher than what a primary care or non-specialty doctor would have you reach.

Based on treating roughly 15,000 patients, we’ve found that the average optimal range for men is around 800 ng/dL – 950ng/dl. However, this isn’t a hard and fast rule, and it depends how the patient is responding to Testosterone replacement therapy.

That’s why we don’t offer cookie-cutter programs – because each patient has specific needs and unique optimal ranges.

Seems that is a typical issue here where treating the numbers is more important than treating the symptoms. Optimal should be at the point in which you no longer experience symptoms and that is, as in most things with the human body, very independent.

I’m not sure this point sums it up—if anything it goes against what I was trying to say because they endorse the “high-normal” theory because they claim that 800-950 is generally the best place for testosterone levels.

I agree that a level of 265 (or 365 for that matter) should probably treated when a man is symptomatic. But why is 916 any better than 265? Who says that it’s better and healthier to have high normal testosterone levels relative to low normal testosterone levels? The prolactin range is generally 3-20 (I forget the units)—does anybody ever aim for a prolactin of 20 just because it is “high-normal”?

I honestly think statements like the above epitomize many clinics desire to cater to certain mens’ desire to have a high testosterone level, and not necessarily to help them achieve full symptom relief.

 

[JRos895]

I've been arguing in favor of this viewpoint for some time now. We know that testosterone interacts with a multitude of other hormones, so it's not a stretch to suggest that an excess of testosterone relative to what's appropriate for an individual is going to cause problems. I've also argued that average testosterone levels are already optimized by evolution, selected to give the best chance of reproductive success, which I further argue is a decent marker for overall success in life. There's a possible counter-argument, which says that conditions have changed for recent generations, with less exercise, poor diets, obesity and endocrine-disrupting chemicals all contributing to emasculation. Nonetheless, I'd say this is an argument for being a little above average, not for putting everyone in the top 10%. And there are still going to be some men who do better with below-average levels. This should be acknowledged, and the low-and-slow approach should be applied to TRT as a matter of course.

Thank you @Cataceous for your thoughtful point.

I wonder if one reason testosterone levels have been falling in recent decades is perhaps because it is actually healthier to have slightly below average levels of testosterone. No doubt there are negative factors causing the fall in testosterone (e.g., obesity), but perhaps also because it has become evolutionary disadvantageous to have levels of 800/900+.

I think one day we will look back and realize how unhealthy it was to aim for “high normal” (800-1000) testosterone levels in the same way we look back today and realize how unhealthy it was to manipulate estrogen into the “low normal” range (10-15).

 

[bruin]

My regular range is about 1100.
about 3 years ago my Dr brought this up, "that my level was very high and he had a concern"
The brief discussion was that historically, for years I had been on that level. I have never had a negative side effect and never been on an inhibitor. I feel great all systems GO, the residual lab findings always reflected "normal ranges"
His response was that obviously I was one of those individuals that functions well at the present results.

 

[Cataceous]

...
Based on treating roughly 15,000 patients, we’ve found that the average optimal range for men is around 800 ng/dL – 950ng/dl. ...

I wonder how many of these men tried lower levels for >2 months in order to have a valid point of comparison? What fraction started out higher and titrated down until they felt better, but not necessarily best? Based on reports on Defy's default protocols I suspect the latter category is highly overrepresented. Fifteen thousand cases would have good statistical power if evaluated with scientific rigor, but without the details I see no need to be overly credulous.

 

[BigTex]

I’m not sure this point sums it up—if anything it goes against what I was trying to say because they endorse the “high-normal” theory because they claim that 800-950 is generally the best place for testosterone levels.

I agree that a level of 265 (or 365 for that matter) should probably treated when a man is symptomatic. But why is 916 any better than 265? Who says that it’s better and healthier to have high normal testosterone levels relative to low normal testosterone levels? The prolactin range is generally 3-20 (I forget the units)—does anybody ever aim for a prolactin of 20 just because it is “high-normal”?

I honestly think statements like the above epitomize many clinics desire to cater to certain mens’ desire to have a high testosterone level, and not necessarily to help them achieve full symptom relief.

I am not so sure men desire to have high numbers rather than not having the symptoms of low T. Most men go to clinics basically as un-informed and wanting medical help because they feel bad.

In the science of the human body there is a law called the law of individuality, meaning every object whether natural or man-made has a unique quality or characteristic in it which is not duplicated in any other object. When you say that 800-960 may not be healthy and lower amounts may be better you are completely discounting individuality between living organisms. If you drop down to say 500 and still have symptoms is that still optimal/healthy? Since we don't have any evidence that 800-900 is not healthy for those that have no symptoms at that range we can't just assume it is unhealthy, especially if no unhealthy side effects exists. There are no meta-analysis studies, controlled Trials or Observational studies so observation/expert opinion become our guide. 15,000 subjects is a pretty large sample size. I am sure the experts at Defy look at all aspects of dosing at any level including unhealthy side effects. You have absolutely got to treat the symptoms and not worry about a number. Unwanted side effects must be taken into account. I have no idea how Defy does with prescribing dose but I would imagine it is very individual and not some cookie cutter dosing to hit that 800-900 mark. The fact that science has show we all react slightly different to medicine doses tells me that it is very possible that some are completely healthy at higher doses and free of symptoms while others require less.

What is the evidence hierarchy



What part does age play in this whole thing. Is a 27 year old with low T and all the side effects better with a 350 or better off towards the high end where so may any others that age are? Still individuality isn't it? Would it not depend on symptoms and unhealth side effects? Does someone who is 65 need to be at the high end of a 27 year old? It's got to be based on the individual. Again you just can't assume a number is important where there are so many variables involved.

I think you guys should go back and listen again to Dr. Lipshultz's interview again. He talked about a study he did where that examined 1000's of patients T numbers and cardiovascular markers and they found that those with higher numbers had less cardiovascular abnormal markers. He said the significance was very high. Is that evidence that higher normal doses are not so unhealthy?

Can men <40 year of age have hypogonadal symptoms of low T with a serum T level of 400 or less? Again, there seems to be no clear threshold.

lil40 - Vasectomy Reversal, Infertility, Hypogonadism Treatment, Urologist - Dr. Larry Lipshultz

lil40

www.larrylipshultz.com

Dr. Lipshultz does base line studies of athletes he deals with that do large doses and says it is very rare if non existent that he ever sees any cardiovascular issues. So again, we have seen very little evidence that a high normal or even more is not healthy. Yet we are assuming lower levels are more healthy? Even Lipshultz advises that when you get on TRT to start low and titrate up to the point you have no symptoms and no unhealthy side effects. Again, there is no specific number for this because of the individuality factor.

Is it making men healthier now that TT levels have fallen so drastically in the past 50 years?

In an analysis of data from 4045 AYA men aged 15 to 39 years who participated in the National Health and Nutrition Examination Surveys (NHANES) and had their total testosterone (TT) levels measured during 1999-2016, TT was significantly lower among those in the later (2011-2016) compared with earlier (1999-2000) survey cycles, Soum D. Lokeshwar, MD, an incoming urology resident at Yale School of Medicine, reported. Mean TT decreased over time from 605.39 ng/dL in 1999-2000 to 567.44, 424.96, 431.76, and 451.22 ng/dL in 2003-2004, 2011-2012, 2013-2014, and 2015-2016, respectively, The declining trend was statistically significant.

Elevated body mass index (BMI) was significantly and independently associated with decreased TT levels, with mean BMI rising from 25.83 kg/m2 in 1999-2000 to 27.21, 27.12, 27.81, 27.96 kg/m2 in 1999-2000, 2003-2004, 2011-2012, 2013-2014 and 2015-2016, respectively. Even in men with normal BMI (18.5-24.9 kg/m2), TT levels declined from 664.79 to 529.24 ng/dL between 1999-2000 and 2015-2016.

Declining testosterone levels in AYA men with increased obesity could lead to the early development of cancer. In addition, low testosterone has been associated with diminished libido and may increase the likelihood of erectile dysfunction. Lower testosterone levels also are associated with lower exercise levels.

Patel P, Fantus R, Lokeshwar S, et al. Trends in serum testosterone levels among adolescents and young adult men in the United States. Presented at the American Urological Association 2020 Virtual Experience held in May. Abstract MP78-01.

Fantus R, Chang C, Bennet N, et al. The association between exercise and serum testosterone among men in the United States. Presented at the American Urological Association 2020 Virtual Experience held in May. Abstract PD25-03.

 

[BigTex]

I wonder how many of these men tried lower levels for >2 months in order to have a valid point of comparison? What fraction started out higher and titrated down until they felt better, but not necessarily best? Based on reports on Defy's default protocols I suspect the latter category is highly overrepresented. Fifteen thousand cases would have good statistical power if evaluated with scientific rigor, but without the details I see no need to be overly credulous.

It might be interesting to hear from someone at Defy on this since we can only guess.

 

[Cataceous]

... When you say that 800-960 may not be healthy and lower amounts may be better you are completely discounting individuality between living organisms. If you drop down to say 500 and still have symptoms is that still optimal/healthy? ...

A rough statistical approach suggests that total testosterone of 800-950 ng/dL puts something like 85% of men above their natural youthful levels. How then is this a reasonable target, especially for the average guy just starting TRT? Isn't it just an extension of the more-is-better thinking surrounding testosterone? Many guys suffer for it, as documented in the forums. Instead, why not cater to the 85% and have an initial target of 500-600 ng/dL—or free T equivalent? A large majority would no longer have symptoms of hypogonadism. With that baseline established, those wanting to try higher levels might be better able to recognize any tradeoffs involved.

 

[JRos895]

From what I’ve read on the forum, it seems like many of Defys starting protocols surpass the upper limit of what might be considered a reasonable high-dose. 140mg a week seems like a commonly described Defy protocol, whereas I would consider 100mg to be a reasonable high-dose.

 

[Systemlord]

140mg a week seems like a commonly described Defy protocol, whereas I would consider 100mg to be a reasonable high-dose.

A 75 mg weekly protocol has my trough numbers at 454, not a bad trough level, 100 mg would easily at put me at or slightly above 1000 ng/dL 1-2 days after my injection since my trough levels were 697 ng/dL.

A 140 weekly protocol would likely keep me well above the normal range for the majority of the week.

 

[BigTex]

A rough statistical approach suggests that total testosterone of 800-950 ng/dL puts something like 85% of men above their natural youthful levels. How then is this a reasonable target, especially for the average guy just starting TRT? Isn't it just an extension of the more-is-better thinking surrounding testosterone? Many guys suffer for it, as documented in the forums. Instead, why not cater to the 85% and have an initial target of 500-600 ng/dL—or free T equivalent? A large majority would no longer have symptoms of hypogonadism. With that baseline established, those wanting to try higher levels might be better able to recognize any tradeoffs involved.

I don't think 800-950 is a target at all, as you said 85% seem to do well here. Would they do better at a lower level? Since we don't know that the 85% would have be
asymptomatic at 500-600, we can't assume that a lower dose would have caused that. As Dr. Lipshultz advised, always start out on the low end and titrate to the point there are no my symptoms and no unhealthy side effects. This is very individual and seems like a logical approach. I would bet money that Defy uses this exactly approach. Any clinic that is using 800-950 as a target IMHO is taking the wrong approach. That to me is no different from starting everyone on on 150mg of test cypionate every 7 days. Some do well on that and some have unwanted side effects. Again, I have no idea how Defy prescribes TRT but I would think they base their prescription on a very individual basis.

Myself, I hit ~950 using 40mg,every 5 days. Most are prescribed more than that, I went in at 320 and was diagnosed as androgen deficient and had all of the common symptoms In my case, I had unhealthy side effects with a low dose that most don't even react to. I had to completely stop to get rid of the sides. Were the symptoms gone at 950? Absolutely, but the unhealthy health effects were not. So where do I go from here.....20mg every 5 days? Or try a different ester? I have dropped down to 400 and 500 and felt like crap. Should I just get over it because the numbers are more "normal"? When medicine starts taking that approach, I will have to go back to self medication.

Are youthful levels too low (Reference Range: 250-827 ng/dL- Quest)? Not long ago it was higher that than Seems youthful have fallen dramatically in the last 50 years. That has been shown to be very unhealthy yet the FDA keeps lowing the bar on the high end. What happens when you base your dosing off a number and guys still have symptoms? Isn't it best to treat symptoms and not worry about numbers? The FDA abstractly determines that only people with less that 300 have low T and will have low T symptoms. Therefore, insurance won't cover the guy who has a 400 level but the same symptoms as a guy who has a level of 100. Yea, I know we are trying to stop any kind of abuse but in the process are we not throwing the 400 level, symptomatic hypogonadal guys under the bus and telling them their problem can't exist because that number is too high? What does a doctor do, send them home and tell them to go UG. This seems to be a big problem in this industry that we treat numbers and not symptoms. The number is irrelevant high or low if you still have symptoms.

 

[BigTex]

From what I’ve read on the forum, it seems like many of Defys starting protocols surpass the upper limit of what might be considered a reasonable high-dose. 140mg a week seems like a commonly described Defy protocol, whereas I would consider 100mg to be a reasonable high-dose.

I was started out with 100mg/10 days and developed side effects. Once started, they are hard to get rid of. So how do we take into account individual difference from one human to another? Once again, we are making assumptions about what Defy does but we have no data on what how they make protocols. 100mg for you might be a reasonable high dose but apparently it was way to much for me. What about the guy who still has symptoms?

 

[Systemlord]

I was started out with 100mg/10 days and developed side effects. Once started, they are hard to get rid of. So how do we take into account individual difference from one human to another? Once again, we are making assumptions about what Defy does but we have no data on what how they make protocols. 100mg for you might be a reasonable high dose but apparently it was way to much for me. What about the guy who still has symptoms?

It would appear the protocols Defy dishes out are diverse, yet Dr. Saya has said before in most of his patients, that biomarkers are healthier, men feel better with Free T levels at or slightly above the normal ranges.

This gives some credibility to my thread, “At what Free T level do you feel optimal”, where 68.2% of men on this forum said they feel their best.

 

[BigTex]

Thanks you @Systemlord. As I suspected, Dr. Saya and his team are treating symptoms and not numbers and watching for unhealthy biomarkers.

 

[Cataceous]

... As Dr. Lipshultz advised, always start out on the low end and titrate to the point there are no my symptoms and no unhealthy side effects. This is very individual and seems like a logical approach. I would bet money that Defy uses this exactly approach. ...

I would take that bet. There are many posts on here in which Defy newcomers describe starting with doses well over 100 mg/week. What is the justification for supraphysiological dosing right from the start—when it's widely believed that titrating downwards is more difficult than titrating upwards? I'm still a supporter of Defy, but this is one area where our views appear to diverge.

 

[Fernando Almaguer]

Dr. Lipshultz started me on 200mg/week and later 1mg anastrozole per week and 20mg tamoxifen per day. I guess they were trying to kill my gyno lol

 

[Blackhawk]

Dr. Lipshultz started me on 200mg/week and later 1mg anastrozole per week and 20mg tamoxifen per day. I guess they were trying to kill my gyno lol

This might imply that his concept of starting low is in relation to AAS use.

"starting low" is not well defined.