I think we agree more than disagree here so I’ll start with that. However, I don’t think sitting at the top of the range is necessarily “absurd” as you like to constantly say. I’d also say we don’t have good solid data on what are considered top level testosterone levels for healthy young males. We’ve been wrecking our endocrine systems with chemicals and various substances for 100+ years. How long have we been getting testosterone levels for the population. Out of those tests, how many were done in healthy young males? For the ones that were done in healthy young males, how many were done with accurate testing methods? For the ones that were done in healthy young males, which ones were done at a time of day when they were actually at their peak? The list of questions could go on and on…but point being, there’s no way to go back and find a fully optimized society of natural males and test them to see what their levels were. And even if we could, that doesn’t mean being at or slightly above those levels would not be even better, or that maintaining those levels for the entire day instead of for a brief snapshot. And yes, I understand the down(and up)stream impacts on other hormones, but that is a different discussion outside of a strictly best level conversation. Finally, you say 30 is absurdly high. Is 29 absurdly high? How about 28? 27? Regardless of where you decide to drop the “absurd” label, that is a subjective take.
Again we are talking troughs/steady-state here whether injecting daily, EOD, twice-weekly, M/W/F, once weekly not a daily short-lived peak!
A trough FT 30-30+ ng/dL is absurdly high compared to where a healthy young male would sit 12 ng/dL (paper posted below) and this is tested using the most accurate assay, gold standard direct state of the art ED LC-MS/MS assay in healthy men, blood drawn in the early AM!
Again outliers are the ones that would be hitting the 90-95 th percentile and this would be far and few.
Most healthy young males are hitting a TT 500-600 ng/dL (peak), even going back to the 70s when testing was first available you would be looking at 600-800 ng/dL.
Take those TT 500-800 ng/dL (short-lived peak) and thrown in for shits sake a normal SHBG and calculate their FT using the go to linear law-of-mass action cFTV and none of these men would be hitting a peak FT of 20 ng/dL.
Top it off that cFTV tends to overestimated slightly compared against a standardized direct state of the art ED assay so FT would be slightly lower than the cFTV value given!
There is a reason we have a natural 24 hr circadian rhythm with T levels peaking in the early AM.
T was never meant to be elevated let alone amped up 24/7!
Fine balance we are talking about here especially when it comes to disruption of the hormonal milieu let alone neurotransmitters especially dopamine!
Again running too high a trough/steady-state FT level can be just as bad in many ways as running too low a level especially when it comes to libido and erectile function let alone mood!
Again I am not against one running high-end/slightly above trough FT levels if they truly feel great overall, blood markers are healthy and they are not struggling with any sides.
Also need to keep in mind injection frequency when speaking about trough as again there is a big difference between one running a high (20-25 ng/dL) or better yet absurdly high (30-30+ ng/dL) trough FT injecting daily vs every 3.5 days let alone once weekly!
Stressing the point here that a
trough/steady-state FT 30-30+ ng/dL is absurdly high compared to where most healthy young males would sit at peak and that is short-lived to boot!
Clear as day here!
Look over the 2 papers posted below, healthy males, direct state of the art ED LC-MS/MS assay was used, blood was drawn in a fasted state in the early AM!
ECE 2024 Poster Presentation
www.endocrine-abstracts.org
*Serum samples were analyzed from healthy men participating in the SIBLOS/SIBEX and EMAS studies, both population-based cohort studies
* mFT levels were measured in 867 men using ED LC-MS/MS as previously reported (1). Subsequently, 95% reference ranges were determined using the non-parametric method
Reassessment of FT in women and men with state-of-the-art methodology confirms previously established FT percentages but highlights limitations of differen
academic.oup.com
Reference: 1. Fiers T, Wu F, Moghetti P, Vanderschueren D, Lapauw B, Kaufman JM. Reassessing Free-Testosterone Calculation by Liquid Chromatography–Tandem Mass Spectrometry Direct Equilibrium Dialysis. J Clin Endocrinol Metab. 2018;103(6). doi:10.1210/jc.2017-02360
Age-stratified reference ranges for directly measured serum free testosterone in healthy men (2024)
Joeri Walravens, Gido Snaterse, Nick Narinx, Leen Antonio, Tim Reyns, Tom Fiers, Jean-Marc Kaufman & Bruno Lupauw
Introduction
Determination of serum (calculated) free testosterone (FT) in clinical practice has been suggested by several clinical guidelines for the diagnosis of male hypogonadism in men with borderline total T concentrations and in situations with altered sex hormone-binding globulin, as it correlates better with androgen exposure than total T. The gold-standard for the determination of FT levels is considered to be directly measured free testosterone (mFT) using equilibrium dialysis followed by mass spectrometry (ED LC-MS/MS). However, no widely accepted reference ranges are available for this clinical parameter. We established mFT reference ranges for healthy men aged 18 to 69 years.
Objective
To establish reference ranges for measured FT in serum of healthy adult men.
Methods
Reference ranges were determined following Clinical & Laboratory Standards Institute guideline C28-A3c per age decade. Serum samples were analyzed from healthy men participating in the SIBLOS/SIBEX and EMAS studies, both population-based cohort studies. Exclusion criteria were medications or conditions that affect sex steroid metabolism or a BMI larger than 35 kg/m2. mFT levels were measured in 867 men using ED LC-MS/MS as previously reported (1). Subsequently, 95% reference ranges were determined using the non-parametric method.
Results
We present 95% mFT age-stratified reference ranges. These reference ranges show an expected, decreasing trend of mFT with aging. Lower limits and median mFT decrease at a remarkably stable rate of, on average, 12% per decade up into the 6th decade of life. However, in the upper limit, a marked decrease of 25% occurs after 39 years, followed by smaller decreases of 6% per decade in older age categories.
We present 95% mFT age-stratified reference ranges
Age category (years) | Median mFT (ng/dl) | 95% mFT reference range (ng/dl) |
18-29 (n=140)
30-39 (n=252) | 12.0
9.8 | 6.7-25.3
4.9-18.5 |
40-49 (n=207) | 8.1 | 4.3.14.2 |
50-59 (n=146) | 7.1 | 3.8-12.8 |
60-69 (n=126) | 6.4 | 3.4-11.7 |
70-79 (n=125) | 5.6 | 2.7-8.7 |
Conclusion
We have determined mFT reference ranges in healthy men aged 18 to 69. These reference ranges are a first step to improving the framework for further development and integration of free testosterone measurements and calculations in clinical practice.
Again how many healthy young males are running around with a peak FT 25.3 ng/dL!
The median FT value for healthy young men 18-29 years is 12.0 ng/dL!
Throw the Jasuja and Bhasin 2022 study in there too!
Again healthy males, direct state of the art standardized ED LC-MS/MS assay was used, blood was drawn in a fasted state in the early AM!
Critical point here!
Look at where the men 19-39 years in the 50th (14.1 ng/dL), 75th (19.0 ng/dL), 90th (24.0 ng/dL) and 97.5th (30.9 ng/dL) percentile values for absolute FT values sit!
* In healthy nonobese men, 19 years or older, the 2.5th, 10th, 25th, 50th, 75th, 90th and 97.5th percentile values for absolute free testosterone were 66, 91, 116, 141, 190, 240, and 309 pg/mL, respectively (Table 3).
Again how many healthy young males are running around with a peak FT 24.0-30.9 ng/dL!
The 50th percentile value is 14.1 ng/dL!
https://onlinelibrary.wiley.com/doi/abs/10.1111/andr.13310
Reference Intervals for Free Testosterone in Adult Men Measured Using a Standardized Equilibrium Dialysis Procedure (2022)
Ravi Jasuja, Ph.D.; Karol M. Pencina, Ph.D.; Daniel J. Spencer, BS; Liming Peng, MS; Fabiola Privat, BS; Waljit Dhillo; MD, Ph.D.; Channa Jayasena, MD, Ph.D.; Frances Hayes, MD; Bu B. Yeap, MB, BS, Ph.D.; Alvin M. Matsumoto, MD; Shalender Bhasin, MB, BS
Again you heard it here first only at Nelson's
ExcelMale! @
Nelson Vergel Was going to drop this bomb a few days ago but you let down the curtains early LOL! https://onlinelibrary.wiley.com/doi/abs/10.1111/andr.13310 Reference Intervals for Free Testosterone in Adult Men Measured Using a...
www.excelmale.com
ABSTRACT
Background
Free testosterone (FT) determination may be helpful in evaluating men suspected of testosterone deficiency, especially in conditions with altered binding-protein concentrations. However, methods for measuring FT by equilibrium dialysis and reference intervals vary among laboratories.
Objective
To determine reference intervals for FT in healthy, nonobese men by age groups as well as in healthy young men, 19 to 39 years, using a standardized equilibrium dialysis procedure.
Methods
We measured FT in 145 healthy, nonobese men, 19 years or older, using a standardized equilibrium dialysis method performed for 16 hours at 37ºC using undiluted serum and dialysis buffer that mimicked the ionic composition of human plasma. FT in the dialysate was measured using a CDC-certified liquid chromatography-tandem mass spectrometry assay.
Results
In healthy nonobese men, the 2.5th, 10th, 50th, 90th, and 97.5th percentile values for FT were 66, 91, 141, 240, and 309 pg/mL, respectively; corresponding values for men 19 to 39 years, were 120, 128, 190, 274 and 368 pg/mL, respectively. FT levels by age groups exhibit the expected age-related decline. FT levels were negatively associated with body mass index, age, and SHBG levels. Percent FT was lower in middle-aged and older men than young men adjusting for SHBG level.
Discussion
Further studies are needed to determine how these reference intervals apply to the diagnosis of androgen deficiency in clinical populations and in men of different races and ethnicities in different geographic regions.
Conclusion
Reference intervals for free FT levels (normative range 66-309 pg/mL [229- 1072 pmol/L] in all men and 120-368 pg/mL [415-1274 pmol/L] in men, 19-to-39 years), measured using a standardized equilibrium dialysis method in healthy nonobese men, provide a rational basis for categorizing FT levels. These intervals require further validation in other populations, in relation to outcomes, and in randomized trials.
Put the nail in the coffin here!
This is coming from the man who would be considered the father of testosterone who has made huge contributions regarding testosterone therapy and men's health let alone has treated 1000s of men over decades!
Would be considered one of the top heavyweights when it comes to (research/clinical experience) in the field of hormone replacement therapy!
Puts most endos to shame when it comes to treating symptoms vs numbers!
Even then one of the main points he always stresses:
Dr.Abraham Morgentaler
* what's important to understand though is that the concept of testosterone therapy in theory is designed to replicate youthful levels of testosterone to help people who are deficient in this hormone, the goal isn't to make them into supermen and the real question is why do people want to go above normal if at all, much of the concept of treating up lets say a 1000 let's say our normal upper limit, in the anti-aging community or age management community there are some people who believe the there's an optimal level of testosterone that may be 1200 or 1500 or even I've heard 1800 and the basis for that is WEAK!
