T
Could you please expand on this?
T
tareload
Guest
If you search for the term adrenergic on here or autonomic dysfunction / adrenergic on TNation and look at posts from Unreal... or myself you'll find a lot of content and all the literature. I'll try to link some example posts later for convenience later.
EDIT:
Ended up in ER last month
Ok new update. I got blood results back for testing of the pheochromocytoma and those all came back in range. I just received back the urine test results but they are saying something a little different. My urine metanephrine was 215(High) range (58-203). I message my GP about this and he...
www.excelmale.com
Nandrolone Experiences
studies agree with me. So no I won't speak for myself lol, I seldom do when i make a claim it's what data say. But yeah high dose test will blow you up like a water buffalo. I like my gains lean, my prostate small, and my hair juvenile! Couldn't care less about strength gains, I don't need to...
www.excelmale.com
Nandrolone Experiences
studies agree with me. So no I won't speak for myself lol, I seldom do when i make a claim it's what data say. But yeah high dose test will blow you up like a water buffalo. I like my gains lean, my prostate small, and my hair juvenile! Couldn't care less about strength gains, I don't need to...
www.excelmale.com
nandrolone- atrophy in quads? Also, legalities and terminology
I’ve been on 25mg Anavar daily for 2 weeks, and it’s awesome. Strength is going up during each workout. I started BPC today for a nagging back injury. I am turned off by Deca’s reported side effects What’s the rest of ur protocol look like?
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Test C, Tren A, Oxandrolone
I know @unreal24278 posted this study a while back and it’s a real gem (kind of hiding in plain sight in terms of tangible measurements on an observational study) in my opinion testing on actual humans. Self reported dosages per week were modest on the AAS arm: Measurable and significant...
forums.t-nation.com
What is TRT and What is NOT TRT
Anyone able to answer my question about the change in FSH ref range?
forums.t-nation.com
What is TRT and What is NOT TRT
@wolf359; Thanks for the suggestions. However, citrulene or arginine worsen my bipolar illness, making me hyper(citrulene) or manic(arginine). I’m taking liothyronine(T3) because several of my doctors believe that I have cellular thyroid resistance. Labs are useless because they can’t reveal...
forums.t-nation.com
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However, 1,200 ng/dL is pretty much double the norm, and that's for healthy young men. Beyond that, you'd be hard pressed to find many men naturally over 1,000 ng/dL who don't have elevated SHBG, and thus more pedestrian free testosterone.
I again reject that "maintaining mid-range physiological T levels" can be characterized as micro-dosing. We would have to debate which sample of men is actually skewed. In the broader TRT world the number of men using low-concentration testosterone gels is significant, and this cohort is largely maintained at physiological levels. The men on dated protocols using infrequent injections are the ones skewing the numbers. They inject non-physiological amounts of testosterone in order to maintain physiological levels at the end of each injection cycle. The supraphysiological peaks are largely ignored. The modern Xyosted product makes this glaringly obvious, with its doses limited to 50, 75 and 100 mg TE per week.
We discussed this previously and I explained that I have minimal objections to experienced guys exploring moderately higher doses if they have already tried a range of physiological levels and are willing to accept whatever nebulous risks may exist. There are U-shaped mortality curves for most hormones, even if causality isn't established. What I object to is men being started on TRT at higher levels, even if in range. This is the opposite of the low-and-slow approach promoted by Dr. Crisler and others. What happens to those men who would feel best with numbers that are average or below—probably about half the population? They get screwed by the high-and-fast approach, never really experiencing what's best for them. By the time they decide they don't feel that great at higher numbers their bodies may be acclimated to the higher doses. Then the withdrawal symptoms from dosing lower are misinterpreted as the lower dose not working. And round and round they go.
While the norm or statistical mean indicates average testosterone levels, the mean does not serve as the single generalizable marker for physiological levels of T. It simply serves as the average derived from men across the range. In fact, in teen males natural TT can reach levels of 1,200 ng/dL.
That notwithstanding, I agree fully with your points pertaining to the perspective that guys should not be started too high when starting testosterone replacement therapy.
My primary stance is that men on this forum, or any other forum, who are experiencing side effects or suboptimal results from TRT should explore, and be encouraged to explore, options to optimize their replacement therapy. These options might include adding is adjunct therapies such as HCG, DHEA, pregnenolone, or gonadorelin. Other options could include exploring different esterfied preparations of testosterone, combined ester preparations, modifying dose frequency, and titrating dose down OR up.
Very low dose therapy aimed at mid-range physiological levels is a step in the right direction for some, but should not be used prescriptively for all.
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Here's a counterexample in which a CDC-harmonized test has teenagers' range top as 785 ng/dL while for adults it's 916 ng/dL.
You follow some good advice with an oxymoron. "Very low dose therapy" implies lower-range and below-range levels. Normal-dose therapy implies mid-range physiological levels. Is Zyosted "very low dose"? Tell me there's not this skewed perspective about testosterone, in which the more-is-better mindset leads to attempts to redefine normal. You wouldn't be talking this way about other hormones. "Well I think I'll inject some estradiol so that I can be supraphysiological and maybe feel better." On the contrary, with estradiol we've seen guys fretting endlessly about higher levels and going to great lengths to restrict it to "normal" levels. Hopefully such thinking will be supplanted by an emphasis on balance. If we don't know what's optimum for us then let evolution be our guide, at least initially. Average numbers for healthy young individuals were selected over time to give the best odds of successfully procreating and raising offspring. This isn't such a bad proxy for overall success in life, given that historically you had to attract and retain a mate, as well as provide for her and the offspring.
Face validity for the CDC test is very low considering it’s generally accepted that sex hormones peak in late adolescence.
It is also known that reference ranges have been consistently titrated downward to reflect what is normal for our population. As our population has become ‘bigger’, these ranges have been shifted downward reflect what is normal for people who are less lean and have a higher BMI. As such, our norm or mean has shifted downward, not necessarily reflecting what is optimal but perhaps reflecting simply what is normal for a ‘less lean’ population. For example, prior to 2017 LabCorp used the range of 348-1197 ng/dL which was obtained through the Framingham Heart Study using lean males. However, in 2017 it adopted a much lower reference range to reflect a higher BMI population’s testosterone, resulting in a range of 264-916 ng/dL. Again, that downward shift does not necessarily reflect a healthier cohort.
Evolution has been supplanted with inorganic changes that have occurred at a rapid pace. Highly energy dense foods and sedentary lifestyles leading to higher BMIs, obesity, and its associated morbidities are not a normal part of evolution. As higher BMIs have led to a population norm of lowered testosterone levels, this does not necessarily reflect healthier population, one that is to be modeled with reverence.
Many men on TRT feel great at higher levels than the statistical mean. Some experience side effects. Should some of these men explore levels at the mean? Yes. Will everyone feel their best at the mean? No.
One issue is that the test for the older range was not harmonized. But let's take a closer look at its source. The mean free testosterone for this young cohort is 14.2 ng/dL. Question: What total testosterone does this correspond to when SHBG is average, about 30 nMol/L? Answer: 625 ng/dL. What about two standard deviations higher, at the top of the reference range? Answer: 940 ng/dL. This demonstrates that the high end of total testosterone is skewed by individuals with elevated SHBG.
It's assumed that higher body fat in participants in the newer study leads to higher estradiol and lower testosterone production. However, another factor is that BMI is negatively associated with SHBG. Lower SHBG drives down total testosterone even as the production rate stays the same.
A few key takeaways…
…a total testosterone of 1197 ng/dL is not double physiological testosterone levels in men. It is merely double the mean.
…the mean tells you the statistical average testosterone levels in a cohort. It does not, however, serve as the flagship level for health and wellness.
…face validity is very low for the CDC harmonized test given that it is generally accepted that sex hormones peak in late adolescence. As such, validity of the study is questionable.
…any man on TRT experiencing negative side effects may benefit from shooting for mean levels of testosterone. However, achieving mean T levels does not work for everyone, and there are examples even in this skewed sample of men on Excelmale that have not achieved resolution to their side effects by titrating downward. There are in fact, examples of men that have experienced worsened side effects after long trials of downward titration.
…there are a plethora of strategies one may incorporate to achieve an optimized TRT, downwards and upwards titration included.
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Everybody’s different, but if your bloodwork is great and you feel better with more test and there aren’t any negative sides, I don’t see any compelling reasons not to be on the higher end of the spectrum. I think everybody owes it to themselves to experiment with that and find what works best for them, whether that’s lower or higher.
You can’t cleanly compare TT and FT levels between injected test and naturally produced test, either. Just like with thyroid hormones in the blood, there are so many other things going on that are different between supplementing it and what happens when it’s naturally produced that it’s not as simple as that. Someone with a natural TT of 1000 and that same someone with an injected TT of 1000 aren’t going to be the same.
He technically still is microdosing compared to the most common dosing schemes, which have historically been one bolus dose of 200 or so every 2 weeks. Debating whether the total amount is still too high seems like another thing. He’s injecting a very small amount of oil every day.
You can’t cleanly compare TT and FT levels between injected test and naturally produced test, either. Just like with thyroid hormones in the blood, there are so many other things going on that are different between supplementing it and what happens when it’s naturally produced that it’s not as simple as that. Someone with a natural TT of 1000 and that same someone with an injected TT of 1000 aren’t going to be the same.
He technically still is microdosing compared to the most common dosing schemes, which have historically been one bolus dose of 200 or so every 2 weeks. Debating whether the total amount is still too high seems like another thing. He’s injecting a very small amount of oil every day.
madman
Super Moderator
T levels in healthy young males peak around age 19.
Even then everyone needs to keep in mind that such levels are not maintained 24/7 let alone it is far from common that a healthy young male is hitting a peak TT 1000+ ng/dL.
T levels of a healthy young male follow a diurnal 24 hr circadian rhythm and will start to rise gradually throughout the night reaching a short-lived peak between 6-8 am and start declining later in the day well into the early evening reaching a nadir between 6-8 pm.
Fluctuations from peak--->trough would be around 20-25%.
When getting lab work done to see where natural endogenous levels sit testing should be done between 6-10 am as we want to test at the peak.
Just to be clear before everyone keeps on blaming this that and the other people need to be aware that the main reason for the lower reference range adopted from the more recent 2017 study comes down to harmonized reference ranges and standardized assays as testosterone concentrations were measured using a higher-order liquid chromatography-tandem mass spectrometry method.
*A large study of more than 9,000 men has established harmonized reference ranges for total testosterone in men that when applied to assays that have been appropriately calibrated will effectively enable clinicians to make a correct diagnosis of hypogonadism, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.
Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe (2016)
Thomas G. Travison,1 Hubert W. Vesper,3 Eric Orwoll,4 Frederick Wu,5 Jean Marc Kaufman,6 Ying Wang,4 Bruno Lapauw,6 Tom Fiers,7 Alvin M. Matsumoto,8 and Shalender Bhasin2
Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe - PMC
Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating assays to a reference ...
www.ncbi.nlm.nih.gov
Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men.
Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating assays to a reference method and standard.
Population: The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis.
Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at the Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges.
Results: Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy non-obese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men.
Conclusion: Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.
The reference ranges provide the basis for differentiating low from normal testosterone levels, and are, therefore, essential for making the diagnosis of hypogonadism. We have published reference ranges for circulating testosterone levels generated in healthy nonobese men who were participants in the Framingham Heart Study (FHS) (4); similar data have been published in other populations (5–11). However, an important unresolved question is whether the reference ranges generated in one population of men can be applied more broadly to men in other geographic regions and in other populations. The distribution of testosterone concentrations could vary in men from different regions due to interassay or interlaboratory differences, or biological or environmental factors.
The objective of this initiative of the Endocrine Society was to compare the distribution of total testosterone concentrations in epidemiologic studies that included men from different geographic regions of the United States and Europe and to generate consensus reference ranges for total testosterone levels in men. We anticipated that, notwithstanding the substantial interindividual variation in testosterone levels observed within each cohort, there would also be significant and correctable variation in mean testosterone levels between cohorts owing specifically to differences in measurement technology. We sought to minimize the influence of these systematic differences by harmonizing all measurements to a higher-order standard prior to the estimation of reference ranges.
Accordingly, serum testosterone levels were measured in male participants of four epidemiologic studies: the FHS, the European Male Aging Study (EMAS), the Osteoporotic Fractures in Men Study (MrOS), and the Sibling Study of Osteoporosis (SIBLOS). Because different assays were used for measuring testosterone levels in these four epidemiologic studies and because these assays used different calibrators, the assays were cross calibrated centrally by measuring testosterone levels in serum samples from a subset of men in each cohort in the Centers for Disease Control and Prevention (CDC) Clinical Reference Laboratory using an assay calibrated with higher-order reference materials and using serum-based reference materials as additional accuracy controls.
*By comparing these new CDC-derived values with the original values obtained on these men from each cohort, we developed normalizing equations permitting translation from the original cohort-specific measurements to the CDC standard, and then applied them to the full sample of values in each cohort.
Because testosterone levels decline with advancing age, we first generated reference ranges in healthy nonobese young men, 19 to 39 years, as this approach based on limits derived in a healthy young population has been favored historically for analytes that exhibit clinically meaningful age-related trends, such as estradiol and bone mineral density. Because of the well-known effect of obesity on testosterone levels and on age-related change in testosterone levels, we present age-adjusted reference ranges in nonobese men, and additionally for all men, by decades of age.
General approach
First, fasting morning serum samples obtained from 100 men from each of the four cohorts, in which testosterone levels had previously been assayed locally, were transported to the central laboratory at the CDC. These 100 men with previous assay results from the local laboratory were chosen at random to approximate the distribution of age and other factors within each of the four cohorts. At CDC, testosterone concentrations were measured on each sample using a higher-order (a reference method against which other methods are compared) liquid chromatography-tandem mass spectrometry (LC-MS/MS) method under the supervision of Dr. Hubert Vesper. We then developed transformational equations for each study describing the relationship between the 100 local and 100 central measurements, providing an estimate of the systematic variation in local measurements from the reference standard. These normalizing equations were applied to all testosterone levels measured in each of the four cohorts to generate harmonized values. These harmonized measurements were in turn used to derive standardized, age-specific reference ranges in each of the four cohorts and overall.
FHS
The original FHS cohort was established in 1948 by recruiting 5209 men and women between the ages of 30 and 62 from Framingham, Massachusetts. In 1971, the study enrolled 5124 of the original participants’ adult children and their spouses, who constituted the Second Generation Cohort (Generation 2). The Generation 2 examination 7 was attended by 1625 men between 1998 and 2002. Exclusion of men with prostate cancer undergoing androgen deprivation therapy (n = 8), men receiving testosterone therapy, and men with missing testosterone data (n = 158) resulted in a sample of 1459 for Generation 2.
A Third Generation Cohort (4095 children of Generation 2, referred to as Generation 3) was established from 2002 to 2005 (14) (http://nhbli.nih.gov/about/framingham). Of the 1912 men who attended the first Generation 3 examination in 2002 to 2005, 1893 had total testosterone measurements, and 962 were #40 years, among whom 456 men of Generation 3 were free of cancer, cardiovascular disease, diabetes mellitus, hypertension, hypercholesterolemia, and obesity [body mass index (BMI) .30 kg/m2 ] and constituted the reference sample. The men who were receiving androgen deprivation therapy or had undergone orchiectomy for prostate cancer or were taking testosterone were excluded.
The FHS combined sample was created by combining Generation 2 and Generation 3 samples. Generation 2 examination 7 was attended by 1625 men between 1998 and 2002. Exclusion of men with prostate cancer undergoing androgen deprivation therapy (n = 8), men receiving testosterone therapy, and men with missing testosterone data (n = 158) resulted in a sample of 1459 for Generation 2. This sample of 3352 men (1459 men in Generation 2 plus 1893 men in Generation 3) constituted the FHS combined sample.
Generation of reference ranges in healthy, nonobese (BMI <30 kg/m2 ) young men
First, we selected men, 19 to 39 years, who were nonobese (BMI,<30 kg/m2 ) and free of major comorbidities, as described (4). Because men,<40 years were available only in the FHS and SIBLOS studies, data for 1185 men meeting these criteria from these cohorts were included in this analysis.
Age-specific reference ranges in nonobese men
We computed reference ranges for individuals with BMI,<30 kg/m2 by decades of age (19 to 39, 40 to 49, 50 to 59, 60 to 69, 70 to 79, and 80 to 99 years). There were 6933 men from the four cohorts meeting this BMI criterion. The analyses were first performed within each cohort, and then the cohorts were combined to derive model-based estimates of age trends in population quantiles.
*Table 4 provides age-specific estimates of the percentiles of total testosterone distribution derived from all studies combined, after harmonization, using constrained quantile regression models. As is the case with the exploratory estimates described in Table 3, we observed age-related decreases in concentrations at the lower end of the distributions, whereas the upper centiles were largely stable across the age groups. Thus, among nonobese men, the age-specific 95th percentile estimates lie in a tight range (839 to 850 ng/dL), whereas the 5th percentile estimates vary more substantially, ranging from 304 in men 19 to 39 years of age to 252 in those 70 to 79 and 218 in those 80 and above.
Discussion
These data show that the cross-calibration of assays using a higher-order standard and a higher-order assay in a central laboratory provides a substantial reduction in intercohort variation. This suggests that measurement variation contributes to the previously observed variation in mean testosterone levels among epidemiological cohorts from different geographic regions, the substantial interindividual variation in hormone levels within any cohort notwithstanding. The distribution of harmonized total testosterone values in healthy nonobese young men was very similar between the FHS Generation 3 and the SIBLOS cohorts—2 geographically distinct cohorts. The 2.5th, 5th, 50th, 95th, and 97.5th percentile values in healthy nonobese young men were 264, 303, 531, 852, and 916 ng/dL, respectively (Table 2).
*We conclude that standardized hormone measurements calibrated to a higher-order benchmark, such as that offered by the CDC Clinical Reference Laboratory, provide a rational and feasible approach to generating harmonized reference ranges for testosterone and possibly other analytes.
*The data reported in this work illustrate the promise and feasibility of generating reference ranges using harmonized values that can be applied across different geographic regions of the world to CDC-certified laboratories that use a common calibrator. Such calibrators for testosterone and some other analytes are now available from the National Institute of Standards and Technologies
*In summary, these data demonstrate the feasibility and potential value of generating harmonized reference ranges for testosterone concentrations, whose serum total testosterone concentrations have been measured in a CDC-certified laboratory. There was a remarkable concordance in age-adjusted harmonized testosterone levels among men in four geographically distinct cohorts, suggesting that intercohort variation may be influenced by interassay variation. Further studies of the distribution of testosterone concentrations in other racial and ethnic groups and in populations in other regions of the world are needed to demonstrate the applicability of these ranges to broader populations of men in different regions of the United States and the world.
Also, keep in mind that the authors of the more recent 2017 study were the same ones who contributed to the previously published reference ranges taken from the 2011 study.
*We have published reference ranges for circulating testosterone levels generated in healthy nonobese men who were participants in the Framingham Heart Study (FHS) (4)
Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography-Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts (2011)
Shalender Bhasin, Michael Pencina, Guneet Kaur Jasuja, Thomas G. Travison, Andrea Coviello, Eric Orwoll,* Patty Y. Wang,* Carrie Nielson,* Frederick Wu,* Abdelouahid Tajar,* Fernand Labrie, Hubert Vesper, Anqi Zhang, Jagadish Ulloor, Ravinder Singh, Ralph D’Agostino, and Ramachandran S. Vasan
Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts - PMC
Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based ...
www.ncbi.nlm.nih.gov
TABLE 3. Distribution of total and free testosterone in the FHS reference sample (n=456)
TT 348.3 - 1196.6 ng/dL (2.5/97.5)
Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe (2016)
Thomas G. Travison,1 Hubert W. Vesper,3 Eric Orwoll,4 Frederick Wu,5 Jean Marc Kaufman,6 Ying Wang,4 Bruno Lapauw,6 Tom Fiers,7 Alvin M. Matsumoto,8 and Shalender Bhasin2
Table 4. Model-Based Estimates of Population Centiles for Total Testosterone Concentrations (ng/dL) Based on Data From NonobeseMen (N = 6933) and in All Men (N = 9054) in the Four Harmonized Cohorts
All nonobese men (age 19-39) TT 267-929 ng/dL (2.5/97.5)
Q&A TESTOSTERONE REFERENCE INTERVAL CHANGES (ADULT MALES) (2017)
1. Why is Labcorp changing the testosterone reference interval?
A: Labcorp is changing to the recently standardized reference interval for adult males based upon testosterone assays standardized to the CDC reference method. This change was driven by the consensus effort for accurate testosterone testing, which was endorsed by a group of professional associations, government agencies, and commercial entities in 20210.
One of the objectives outlined within the consensus statement was to establish standardized testosterone reference intervals by age and gender. Travison et al. published a population-based study at the beginning of 2017 which:
*Evaluated more than 9,000 adult male patients from different geographic regions of the United States and Europe.
*Included 1,185 adult males younger than 40 years of age, with a BMI less than 30.
*Utilized testosterone assays harmonized to the CDC reference method.
*Standardized testosterone reference interval for nonobese adult males (19-39 years of age, BMI <30) was calculated as 264-916 ng/dL.
2. Why is Labcorp's reference interval changing to a lower numeric range?
A: Labcorp's previous reference interval was adopted from a 2011 study that included a population of lean healthy males and utilized a testosterone LC/MS-MS assay prior to the introduction of the CDC standardization protocol. The previous reference interval was based on the Framingham Heart Study Population analyzed by Bhasin et al. and was the only comprehensive total testosterone reference interval study available at that point in time. Labcorp adopted this reference interval for testosterone result interpretation and reporting.
In early 2017, Travison et al. demonstrated that obesity is directly associated with lower testosterone levels in male patients, and the new standardized reference interval established included adult males between 19-39 years old with a BMI less than 30. The lower numeric range in the standardized reference interval reflects a difference in average subjects with higher BMIs as well as harmonization to the CDC reference method.
2011 study: TT 348.3 - 1196.6 ng/dL (2.5/97.5)
2016 study: TT All nonobese men (age 19-39) TT 267-929 ng/dL (2.5/97.5)
2011 study: testosterone LC/MS-MS assay
2016 study: testosterone assays standardized to the CDC reference method (higher-order liquid chromatography-tandem mass spectrometry method)
Labcorp: pre-2017 TT 348-1197 ng/dL---> July 2017 TT 264-916 ng/dL
Strengthandlibido
Member
"Someone with a natural TT of 1000 and that same someone with an injected TT of 1000 aren’t going to be the same."
This is where I get hung up. Just how different is it, I wonder. Should we be aiming for normal physiological range, high-normal, or supraphysiological if only slightly so?
madman
Super Moderator
A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years (2014)
Discussion
Using data-driven modeling and analysis, we have derived a normative model of total testosterone throughout the lifespan. We have shown that in the average healthy male testosterone is low in pre-puberty, rises from age 11, and peaks at age 19 at 15.4 (7.2– 31.1) nmol/L [mean (2.5–97.5 percentile)]. Thereafter TT falls slightly to age 40 years to 13.0 (6.6–25.3) nmol/L. We find no evidence to support a progressive decline in testosterone in middle-aged and older men, sometimes termed the ‘andropause’, as TT does not fall significantly in the average man after the age of 40 years. Our analyses show that the 95% prediction limit increases from 18.7 nmol/L at age 40 years to 24.5 nmol/L at age 88 years. This increase in variation with increasing age demonstrates that reference ranges for TT that do not take chronological age into account are inappropriate for the assessment of an individual’s testosterone levels.
*Our model is derived from data from multiple sources of the measurement of TT in over 10,000 healthy males aged between 3 and 101 years. This is both a strength and weakness of the study. The strength is that modeling power is increased by the provision of large numbers of data points for a wide range of ages: it has been previously shown that models that include both prepubertal, pubertal, and adult ages can be used to derive important insights for a restricted age range [47]. The weakness is the approximate heterogeneity of the values obtained from diverse sources, especially as assay conversion factors were used that have known high correlation but are nevertheless inexact. This includes studies that involve convenience samples (e.g. primary care and outpatient attendees) as well as those that involve population-derived cohorts. Further limitations of our approach are that insufficient data were found to model accurately neonatal ages and that we had to exclude potentially useful studies that used in-house assays which lack standardization and harmonization, and for which no conversion formula has been published [48]. Ten of the thirteen studies used as data sources (Table 1) excluded subjects taking medication that could affect the endocrine system, but three studies [5,6,49] (combined n = 2,371 of 10,097) do not have equivalently explicit inclusion criteria. We can therefore not rule out the possibility that a small number of subjects were on medication that increased their TT levels.
Figure 4. The validated model. Our dataset (n = 10,098) of observed total testosterone for ages 3–88 years, split into normative ranges determined by mean predicted values (blue line) and one (red), two (blue), three (green), and four (purple) standard deviations higher and lower than the predicted values. doi:10.1371/journal.pone.0109346.g004
Figure 5. The validated model in centiles. Normative ranges for the model of total testosterone from ages 3–88 years. In the average case (red line) total testosterone remains constant for age .40. However, the variance in normative ranges increases for these ages, with 1st to 99th centile ranges of 5.6–27.6 nmol/L at age 35 years and 4.1–33.1 nmol/L at age 88 years. doi:10.1371/journal.pone.0109346.g005
It’s hard to say because it’s all speculative because despite all the blood tests we take and measurements we have, there’s still always more that we can’t really know or measure, and hormones all interact with one another.
I think everyone should safely experiment over longer periods of time with all of them to see which they personally prefer. Anecdotally, most guys I’ve known do better and feel more normal/good when their free T is higher than some of the normal ranges, at least 25ng/dl as I recall. Definitely not the case for all of them though. I’ve struggled with low cortisol issues and some thyroid anomalies so mine’s been all over the place at the same total test dose, as well as how I felt, showing there’s a lot more going on than simply looking at some reference numbers. Thyroid’s it’s own can of worms too. I also have sleep apnea and can’t stomach a CPAP so at times some doses will make that worse despite everything else better, so there’s that consideration too.
As I recall my doctor uses a relatively small amount for himself, around 100mg a week, because he’s very sensitive to testosterone in his words. He claims to feel amazing all the time. I do better with higher amounts, though I also look like someone that probably did naturally have higher amounts and am a bigger guy. I also probably have lower DHT now since finasteride, and the higher amounts might be making up for it. We’ll see on my next tests where that’s at. I also do better with HCG, where as it makes some guys feel worse.
It’s a series of trade offs, and everyone has to experiment and find which trade offs they personally prefer while maintaining standards of good health, like your blood pressure not being 200/90 and things like that.
madman
Super Moderator
At least now we have the option to use the most accurate testing methods by choosing a lab/assay that has been certified through the CDC Hormone Standardization Program for total testosterone, estradiol, and soon enough the much-needed free testosterone.
How the CDC Clinical Standardization Programs Are Improving Hormone Tests
www.excelmale.com
*CDC Hormone Standardization Program (CDC HoSt) Certified Testosterone Assays (UPDATED 12/2021)
*CDC Hormone Standardization Program (CDC HoSt) Certified Estradiol Assays (UPDATED 12/2021)
*Measuring FT is technically challenging and shows high variability. The CDC clinical standardization program is developing a high throughput method using the gold-standard equilibrium dialysis (ED) procedure with isotope dilution ultra-high-performance liquid chromatography-tandem mass spectrometry (ID-UHPLC-MS/MS)
*Assays that are standardized are designed to provide accurate results, traceable to “true” value-assigned certified reference materials and gold-standard reference methods. Results obtained using standardized methods can be compared across assays, institutions, populations, and past and future test results, thereby improving diagnosis, treatment, and outcomes of patients
*We conclude that standardized hormone measurements calibrated to a higher-order benchmark, such as that offered by the CDC Clinical Reference Laboratory, provide a rational and feasible approach to generating harmonized reference ranges for testosterone and possibly other analytes
*CDC-certified laboratories that use a common calibrator. Such calibrators for testosterone and some other analytes are now available from the National Institute of Standards and Technologies
How the CDC Clinical Standardization Programs Are Improving Hormone Tests
CDC STANDARDIZED TOTAL T and ESTRADIOL ASSAYS and soon to be FREE TESTOSTERONE!
Measurement of Free Testosterone in Serum Using Equilibrium Dialysis Coupled With ID-UHPLC-MS/MS: Comparison Between Equilibrium Devices (2021) Hui Zhou, Ph.D., Ashley Ribera, BS, Amonae Dabbs-Brown, BS, Uliana Danilenko, Ph.D., Hubert W. Vesper, Ph.D. Centers for Disease Control and...
www.excelmale.com
*CDC Hormone Standardization Program (CDC HoSt) Certified Testosterone Assays (UPDATED 12/2021)
*CDC Hormone Standardization Program (CDC HoSt) Certified Estradiol Assays (UPDATED 12/2021)
*Measuring FT is technically challenging and shows high variability. The CDC clinical standardization program is developing a high throughput method using the gold-standard equilibrium dialysis (ED) procedure with isotope dilution ultra-high-performance liquid chromatography-tandem mass spectrometry (ID-UHPLC-MS/MS)
*Assays that are standardized are designed to provide accurate results, traceable to “true” value-assigned certified reference materials and gold-standard reference methods. Results obtained using standardized methods can be compared across assays, institutions, populations, and past and future test results, thereby improving diagnosis, treatment, and outcomes of patients
*We conclude that standardized hormone measurements calibrated to a higher-order benchmark, such as that offered by the CDC Clinical Reference Laboratory, provide a rational and feasible approach to generating harmonized reference ranges for testosterone and possibly other analytes
*CDC-certified laboratories that use a common calibrator. Such calibrators for testosterone and some other analytes are now available from the National Institute of Standards and Technologies
With the median likely close to the average it means that 1,197 ng/dL is around double or more that of half the men. Or looked at another way, any guy going on TRT who pushes his testosterone this high has almost a 50% chance of being at least double his peak youthful levels. The situation is even worse when you look at free testosterone.
See the U-shaped mortality curve for just about every hormone. Do you see any flaws in my argument based on natural selection? Natural selection of the fittest is what led to these averages. If having total testosterone of 1,200 ng/dL were most favorable to success in life then that would be the average.
See @madman's post.
I'm not aware of anyone saying that physiological dosing alone is a panacea. But I think it's a step in the right direction. Certainly it is for the numerous men in the forums who complain of elevated hematocrit or high estradiol. Beyond that you're doubtless aware of my hypothesis that the hormonal disruption of TRT leads to many of the other negative side effects. Testosterone is just one variable out of many. Tweaking them all gets complicated in a hurry. That's why I encourage use of the nasal gel, at least for starters. You can raise your testosterone without causing massive upheaval elsewhere.
WOW! I didn’t expect this type of turnout. Thank you all for the input.
I am 3 weeks in, and starting to feel a little more motivated. I also seem to be, in general, angry. I don’t feel any sides yet. This is my chief concern.
The conversation gravitated towards what is a high/low dose. I have previously been on 140mg weekly as a single dose, so I looked back at old labs. This is 4 years ago:
Free T - 2.88 (.87 - 5.47)
Total T - 1420 (375 - 1000)
SHBG - 53.4 (20-60)
Is there any value in getting labs now that I have completed 3 weeks? Giving consideration to my current regimen of 20mg Enanthate daily, and previous labs in the ranges depicted above on 140mg cypionate weekly - what are your thoughts? Am I overdosed right now?
I am 3 weeks in, and starting to feel a little more motivated. I also seem to be, in general, angry. I don’t feel any sides yet. This is my chief concern.
The conversation gravitated towards what is a high/low dose. I have previously been on 140mg weekly as a single dose, so I looked back at old labs. This is 4 years ago:
Free T - 2.88 (.87 - 5.47)
Total T - 1420 (375 - 1000)
SHBG - 53.4 (20-60)
Is there any value in getting labs now that I have completed 3 weeks? Giving consideration to my current regimen of 20mg Enanthate daily, and previous labs in the ranges depicted above on 140mg cypionate weekly - what are your thoughts? Am I overdosed right now?
Blood levels stabilize in about 5-6 times the half life of the ester you are using. With Enanthate’s half-life being ~5 days, 4-5 weeks into your new regimen is when you should conduct blood work. Your next set of labs will give you a quantitative view of how high you numbers are. If you feel good and are not experiencing negative side effects (e.g., high blood pressure, water retention, very low HDL, psychological issues) then you are likely at a good dose for you personally. However, if you do experience negative side effects, that COULD be an indication that you are taking too much testosterone. (And if that is the case, a reasonable course of action would be to lower the testosterone dosage ~20% to 16 mg daily and reassess 4-5 weeks later).
For most guys, it takes about 12 weeks on a new regimen to feel stable and acclimated. So keep that in mind that you may experience subtle changes in mood and energy until that point.
When were those old labs done relative to the injections?
If your goal is to operate in the realm of normal physiology then yes, you are overdosed. It should be clear from the above exchange that I think it's a mistake to maintain such levels, particularly if you haven't tried a range of normal levels first. A lack of immediate side effects is no guarantee that you won't be harmed in the long run. Even if the risk is low, why conduct such an experiment on yourself without seeing if you can achieve comparable or better results at normal levels? As demonstrated with Xyosted, normal dosing of testosterone enanthate can be in the range of 50-100 mg per week. For daily injections this is about 7-14 mg. Personally I've experimented with injecting as little as 3.7 mg of testosterone per day without feeling hypogonadal. This is the equivalent of 5.1 mg of enanthate.
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