Hematocrit drives Blood Viscosity- Does that Matter in Men on TRT? Effect of Altitude?

tareload · Jul 1, 2021

Does High Hematocrit Lead to Complications for Men on TRT?

I did a trial of 325 mg/day of aspirin for the last 3 maybe 4 months for a number of reasons. I had also concurrently been slowly ratcheting up my TRT dose from 70 mg/week to 100 mg/week over the same time frame. Pulled blood work last week for a 6 month appt and was expecting to be back...

forums.t-nation.com

Update on my experiment with 325 mg/day of aspirin. Potent reduction in Hct while on TRT. One of the few supplements I've tried that really had a significant effect on Hct. Please consider the risk/reward in your own particular case. I'm just providing the anecdotal data from my own experience.

Nelson Vergel · Jul 1, 2021

readalot said:
Potent reduction in Hct while on TRT.

Really? Do you have it with a buffering agent to avoid GI bleeding?

tareload · Jul 1, 2021

Seriously. I was shocked but I am also heterozygous hemochromatosis carrier so perhaps my experience may not be representative for most.

Thanks for asking. I am taking the standard coated aspirin with no additional buffer but I do take 2g of chewable vitamin C twice daily (Costco chewable) which has been shown to potentially protect against GI issues:

Gastrointestinal effects of the addition of ascorbic acid to aspirin - PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been associated with the damage to the gastrointestinal tract. One proposed mechanism of injury to the gastrointestinal mucosa by NSAIDs is oxygen radical-dependent microvascular injury. There is reasonable evidence to...

pubmed.ncbi.nlm.nih.gov

https://onlinelibrary.wiley.com/doi/abs/10.1111/imj.1969.18.3.248

Comparison of nitric oxide-releasing NSAID and vitamin C with classic NSAID in healing of chronic gastric ulcers; involvement of reactive oxygen species - PubMed

1) ROS-induced enhancement in lipid peroxidation plays an important role in the mechanism of gastric damage induced by ASA, 2) vitamin C attenuates the deleterious effect of ASA on ulcer healing due to its antioxidizing activity by mechanism involving preservation of gastric microcirculation and...

pubmed.ncbi.nlm.nih.gov

Also, I take cetirizine off and on (minimum effective dose) for some type of autoimmune issue that hasn't been named yet. It really does the trick for intermittent horrible acid reflux and urticaria. IIRC, speaking with one knowledgeable rheumatologist, he mentioned it may also be protective against GI injury with NSAIDs. I'd have to look up the body of data on that one.

Best wishes Nelson and hope you are doing well!

tareload · Jul 1, 2021

Nelson Vergel said:
Really? Do you have it with a buffering agent to avoid GI bleeding?

A picture to show just how significant the aspirin result was. Peak was on a 100-125 mg/week TC protocol (some of the data points have some ND or oxandrolone thrown in). Dropping down to 70 mg/week put me back down to the 47-48 range. Aspirin plus 100 mg/week TC put me back down to 44-45 pre-TRT baseline. Hydration before testing about the same for all data points (I drink a lot of water and make sure I have to urinate pretty badly when I do the blood draw each time). I'd estimate a 5-7% reduction in Hct with 3 month use of aspirin. But I may be special case with heterozygous HH mutation.

To the reader, hope this helps and be careful with the potential GI concerns (as Nelson mentioned) and kidneys if yours are compromised.

Does High Hematocrit Lead to Complications for Men on TRT?

https://www.urmc.rochester.edu/news/publications/health-matters/daily-aspirin-worth-the-risks Something to think about for those that may have kidney function similar to 80 yr old. 50 mg/day of oxandrolone with anadrol and some test/tren probably not wise with 325 mg/day of aspirin to combat...

forums.t-nation.com

tareload · Jan 28, 2022

See here for additional commentary and some updates from the literature:

high hematocrit/hemoglobin - what to do

my general doc panicked, told me to immediately stop TRT (not my hormonal clinic) wants to refer me somewhere. stopping not an option. I had 2 readings, 1 before blood donation, 1 after: before donation: RBC - 6.40 Hemoglobin - 18.8 hematocrit - 55.8 after donation: RBC - 6.06 Hemoglobin -...

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high hematocrit/hemoglobin - what to do

@ readalot You are responding to something I never said to create a gotcha-moment. I did not claim absence of evidence equals evidence of no risk of high hematocrit on TRT, I merely pointed out that you have no evidence proving otherwise, although to an unaware reader your post implies you do.

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Nelson Vergel · Jan 28, 2022

Recently published poster presentation:

PD20-06 DEVELOPMENT OF SECONDARY POLYCYTHEMIA WHILE ON... : Journal of Urology

An abstract is unavailable.

journals.lww.com

tareload · Jan 28, 2022

Nelson Vergel said:
View attachment 19301

Recently published poster presentation:

PD20-06 DEVELOPMENT OF SECONDARY POLYCYTHEMIA WHILE ON... : Journal of Urology

An abstract is unavailable.

journals.lww.com

CONCLUSIONS:

In the first year after starting testosterone therapy, development of secondary polycythemia significantly increases the risk for MACE and VTE in a matched cohort of men. To our knowledge, this is the first study that demonstrates secondary polycythemia as a possible underlying etiology associating TT and major adverse cardiovascular events. Physicians should counsel men on the small but real risk of MACE and monitor hematocrit among men receiving T therapy.

Substitute the word erythrocytosis for polycythemia in the article above.

See this paper below for more discussion of why this may be an issue. In the first year on TRT, you'd essentially be fitness testing the cardiovascular system by artificially increasing Hct in those who are susceptible (hemochromatosis carriers, those whose Hct is sensitive to exogeneous Testosterone). Those whose vasodilation capacity can't overcome Hct/viscosity increase (inflammation status, etc.) will lose.

Hence, Hct guidelines are not arbitrary (@Jurek Kletsy), they are based on reference range for humans at rest. Going above that may help those achieve better peak performance, but what if the individual's heart in question (or their cardiovascular system) is not in a position to support that higher power output?

high hematocrit/hemoglobin - what to do

@ readalot You are responding to something I never said to create a gotcha-moment. I did not claim absence of evidence equals evidence of no risk of high hematocrit on TRT, I merely pointed out that you have no evidence proving otherwise, although to an unaware reader your post implies you do.

www.excelmale.com

Thanks for sharing @Nelson Vergel.

Nelson Vergel · Jan 29, 2022

TRT and erythrocytosis

Testosterone therapy and secondary erythrocytosis (2021) Joshua White, Francis Petrella, and Jesse Ory Secondary erythrocytosis is one of the most common adverse events associated with testosterone therapy (TT). Upon encountering this, clinicians will often either adjust TT dosing, stop...

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tareload · Apr 4, 2022

https://www.liebertpub.com/doi/full/10.1089/andro.2021.0013

Abstract

Objective: Hematocrit (HCT)/hemoglobin (Hb) ratio in (%/g/dL) is around 3, with high fidelity between measured and derived Hb (applying the conversion using HCT) in various pathologies. We examined changes in HCT and Hb values and HCT/Hb, compared with baseline, in men with adult-onset testosterone deficiency (TD) given testosterone therapy (TTh).
Materials and Methods: Data were analyzed from an observational, prospective registry study at various time points in 353 men with adult-onset TD receiving testosterone undecanoate (median follow-up: 105 months). After establishing baseline HCT/Hb, we compared (cf. baseline) changes in HCT, Hb, and HCT/Hb at 12, 48, 72, and 96 months. Regression analyses determined predictors of HCT and Hb change.
Results: TTh was associated with (p < 0.0001) increases in median HCT and Hb; 44% to 49% and 14.5 to 14.9 g/dL at final assessment, respectively. Regression analyses showed that HCT change was associated with baseline HCT and testosterone levels, while Hb change was associated with baseline Hb, HCT, and testosterone levels. In the total cohort and subgroups, HCT/Hb increased significantly at all time points (p < 0.0001, cf. baseline) with over 90% of men demonstrating increases. Linear regression showed that the ratio of HCT change/Hb change (i.e., difference between HCT at the various time points and baseline value/difference between Hb at the various time points and baseline value), following TTh at each time point was higher than the baseline HCT/Hb ratio.
Conclusion: HCT increase was greater than we anticipated from the established HCT/Hb of 3. We speculate that increased erythrocyte life span with associated higher Hb loss via vesiculation could account for our observation. This could have a bearing when using HbA1c as an indicator in men with adult-onset TD on TTh.

Nelson Vergel · Apr 4, 2022

readalot said:
https://www.liebertpub.com/doi/full/10.1089/andro.2021.0013

Abstract
Objective: Hematocrit (HCT)/hemoglobin (Hb) ratio in (%/g/dL) is around 3, with high fidelity between measured and derived Hb (applying the conversion using HCT) in various pathologies. We examined changes in HCT and Hb values and HCT/Hb, compared with baseline, in men with adult-onset testosterone deficiency (TD) given testosterone therapy (TTh).
Materials and Methods: Data were analyzed from an observational, prospective registry study at various time points in 353 men with adult-onset TD receiving testosterone undecanoate (median follow-up: 105 months). After establishing baseline HCT/Hb, we compared (cf. baseline) changes in HCT, Hb, and HCT/Hb at 12, 48, 72, and 96 months. Regression analyses determined predictors of HCT and Hb change.
Results: TTh was associated with (p < 0.0001) increases in median HCT and Hb; 44% to 49% and 14.5 to 14.9 g/dL at final assessment, respectively. Regression analyses showed that HCT change was associated with baseline HCT and testosterone levels, while Hb change was associated with baseline Hb, HCT, and testosterone levels. In the total cohort and subgroups, HCT/Hb increased significantly at all time points (p < 0.0001, cf. baseline) with over 90% of men demonstrating increases. Linear regression showed that the ratio of HCT change/Hb change (i.e., difference between HCT at the various time points and baseline value/difference between Hb at the various time points and baseline value), following TTh at each time point was higher than the baseline HCT/Hb ratio.
Conclusion: HCT increase was greater than we anticipated from the established HCT/Hb of 3. We speculate that increased erythrocyte life span with associated higher Hb loss via vesiculation could account for our observation. This could have a bearing when using HbA1c as an indicator in men with adult-onset TD on TTh.

I bet these men were on Androgel or Testim

tareload · Apr 5, 2022

Nelson Vergel said:
I bet these men were on Androgel or Testim

Materials and Methods

The data used were from an observational, prospective, cumulative registry study40 of 353 men [median age (IQR): 60.0 (55.0, 64.0), median follow-up (IQR): 105 (78, 141) months] with adult-onset TD (serum TT ≤12.1 nmol/L) given testosterone undecanoate (TU) 1000 mg/12 weeks following an initial 6-week interval). Data were collected at a minimum of 6-month intervals.

tareload · Apr 5, 2022

@Systemlord FYI as something to consider:

https://www.liebertpub.com/doi/full/10.1089/andro.2021.0013

Obviously you'll want to continue tracking fasting glucose and you should get a fasting insulin test. However, your HbA1c may be affected by TRT?

tareload · May 7, 2022

High Hematocrit: Effect on Blood Pressure & Effect of Altitude on Hematocrit

I don't think comparing the same dose per week of 1 IM shot versus 2 subq shots leads to more testosterone. What it does is smoothing peaks and valleys, so testosterone tests may catch what seems more testosterone blood levels. Having lower peaks may lower the chances to stimulate more red...

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GreenMachineX · May 25, 2022

Does hemoglobin play a role in viscosity at all, or just hematocrit? As of 2 weeks ago, my hct was 49.1 and my hgb was 17.7. I've never had a hgb that high with a hct that low before and according to cmp, I was adequately hydrated (or close to it), and not overhydrated.

tareload · Jul 6, 2022

Polycythemia with testosterone therapy increases CV risk

Too bad they used term polycythemia instead of erythrocytosis. Will perpetuate confusion.

Kaplan-Marans, Elie. "Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy. Letter." The Journal of Urology (2022): 10-1097.

DISCUSSION

Whether or not exogenous testosterone causes MACE or VTE is actively debated, with different evidence showing that TT is either protective, neutral or dangerous for cardiovascular or thrombotic outcomes.19 It is possible that a concurrent, independent risk factor may be driving these adverse events. Whether or not secondary polycythemia may be driving this potential risk has never been evaluated in a population of men using TT. Understanding the factors that may cause MACE or VTE in men on TT is critical to understand, not only for patient and prescribers but for future trial designs investigating this association.

We demonstrated that developing secondary polycythemia while receiving TT, defined as a hematocrit over 52%, was associated with increased risk of developing MACE and VTE during the first year of therapy. TT itself, in the absence of polycythemia, did not appear to increase risk of MACE/VTE in hypogonadal men. To our knowledge, this is the first study to establish secondary polycythemia from TT as an independent risk factor for MACE/VTE using a specific hematocrit-based cutoff.

We used a large national database to answer this question, hypothesizing that real-world data would be best suited to address this issue. Men with high baseline hematocrit are often excluded from randomized trials, and in clinical practice pre-treatment blood work is often not done, and guidelines are frequently not followed.20,21 This leaves a large population of men using TT who are not represented by RCTs. Our findings are somewhat supported by prior literature. The TOM (Testosterone in Older Men with Sarcopenia) trial, an RCT that was stopped early due to increased risk of cardiovascular adverse events, included older men with a high incidence of comorbid conditions.22 While this trial only included 209 men, their demographic information is similar in nature to our study, which included a large proportion of men with comorbid conditions. Like most RCTs on testosterone, the TOM trial did not report hematocrit values in those men with cardiovascular events. One systematic review on this topic did not find overall increased cardiovascular risk, however they did find an increased event rate in the first 12 months of therapy, supporting our window of 1 year for evaluation of MACE/VTE.23 Another review reinforced the value of using large databases in answering this question, highlighting that all published RCTs on this topic are underpowered to assess any association with treatment and cardiovascular outcomes.24 This will hopefully be addressed by the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial (NCT03518034), however polycythemia or hematocrit-based adverse events are not listed as an outcome.

It is well established that TT increases the risk of secondary polycythemia,25 with higher rates in longer-acting modalities and lower rates in shorter-acting modalities.16 Multiple national guidelines use elevation in hematocrit as a trigger to stop or change TT in men. TT cessation triggers include 55% from Canadian guidelines,9 54% from endocrine society guidelines and European urology guidelines,5,26 and between 50%–54% from American urological guidelines.10 While the rationale for these cutoffs is not cited in these guidelines, they appear to come from the Framingham heart study, which found an increase in adverse cardiovascular outcomes with a hematocrit of 49% or higher.8 These findings were confirmed in a more recent prospective cohort study, which found an increased rate of overall and cardiovascular-related mortality once hematocrit entered the range of 50%–54%.27 Neither of these studies specifically studied men on testosterone, and thus the currently existing hematocrit cutoffs amongst TT users is arbitrary. For the purposes of our study, we chose a cutoff of 52%, reflecting other published literature, and to ensure a relatively large comparator arm.10,16

The strengths of this study include its use of a large multi-institutional database and being a real-world snapshot of the effects of TT in a U.S. cohort. There is increasing evidence that nonrandomized evidence from large databases can accurately emulate a large-scale RCT, lending validity to these results.28 Detailed propensity-score matching increased the validity of our findings. Lastly, our sensitivity analyses, and analysis of TT-naïve men, support the role of polycythemia as an independent, critical factor in the development of MACE/VTE.

Limitations include the inability to segregate results by type of testosterone prescription. In addition, a large percentage of the men included are Caucasian (86%), and the matched populations have a relatively high comorbidity index, limiting the generalizability of the findings to minorities and healthy individuals. Furthermore, we were not able to match the 2 groups by baseline hematocrit, as the men in the polycythemia group had a higher baseline hematocrit. Therefore, we cannot definitively determine whether the increased risk of MACE/VTE is due to hematocrit reaching 52% or due to men with higher baseline hematocrit starting TT. Regardless, the baseline hematocrit in the polycythemia group was 47.4%, which according to U.S., Canadian and European guidelines does not warrant further investigation before starting TT. Lastly, due to the limitations of the TriNetX database, we were unable to analyze hematocrit as a continuous variable.

Regardless of these limitations, this study lends prescribers a practical approach to informing about risks of TT, and reinforces existing guideline practices of checking hematocrit prior to prescribing.5 It also provides a hematocrit-based cutoff that comes directly from a population of men using TT, and can hopefully allow future guideline statements to remain consistent across recommendations. Future studies that aim to assess cardiovascular outcomes in men on testosterone (such as the ongoing TRAVERSE study, NCT03518034) should perform detailed analysis on hematocrit change to investigate this as a possible association.

CONCLUSION

Men using TT should be aware that they are at a higher risk for MACE/VTE if their hematocrit reaches or exceeds 52% during the first year of therapy. This is especially relevant in men with cardiovascular comorbidities. Hematocrit-based cutoffs should be incorporated into the outcomes of future RCTs investigating MACE/VTE and TT.

Quick video recap:

ShareFile

aua.sharefile.com

Nelson Vergel · Jul 6, 2022

readalot said:
Future studies that aim to assess cardiovascular outcomes in men on testosterone (such as the ongoing TRAVERSE study, NCT03518034) should perform detailed analysis on hematocrit change to investigate this as a possible association.

I have been saying this for years. The studies should also include T/E2 ratios (both hormones measured by LC/MS).

tareload · Jan 1, 2023

Managed hematocrit but not hemoglobin?

Just for fun I had a quick chat with one TRT Doc from the US in FB group, won't mention his name for now, regarding this issue and he said he and his hematologists ain't even worried even upto 60% HC if all other markers, BP are good, and client feels not sides. So basically thats a green pass...

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Related thread.

tareload · Jan 1, 2023

readalot said:
View attachment 15203

A picture to show just how significant the aspirin result was. Peak was on a 100-125 mg/week TC protocol (some of the data points have some ND or oxandrolone thrown in). Dropping down to 70 mg/week put me back down to the 47-48 range. Aspirin plus 100 mg/week TC put me back down to 44-45 pre-TRT baseline. Hydration before testing about the same for all data points (I drink a lot of water and make sure I have to urinate pretty badly when I do the blood draw each time). I'd estimate a 5-7% reduction in Hct with 3 month use of aspirin. But I may be special case with heterozygous HH mutation.

To the reader, hope this helps and be careful with the potential GI concerns (as Nelson mentioned) and kidneys if yours are compromised.

Does High Hematocrit Lead to Complications for Men on TRT?

https://www.urmc.rochester.edu/news/publications/health-matters/daily-aspirin-worth-the-risks Something to think about for those that may have kidney function similar to 80 yr old. 50 mg/day of oxandrolone with anadrol and some test/tren probably not wise with 325 mg/day of aspirin to combat...

forums.t-nation.com

An ethical scientist reports and publishes data that supports AND data that refutes a hypothesis. After my latest round I wanted to give a quick update that 120 mg/week of Test Cyp for 8 weeks plus 325 mg aspirin daily did not result in same promising results I highlighted quoted above. My Hct is again back to 50% so the hypothesis that aspirin supplementation directly reduces RBC production rate is not supported by my data.

My apologies for giving a false hope previously but that is the latest data I have. I will provide a dose response curve with my data as time allows.

tareload · Jan 3, 2023

Since @PeterBond brought up this excellent reference...some highlights from Chap 34.

What do you think the moderate or severe hypovolemia cases mean for your cardiac output and workload? Ask your Doc?

Enjoy.

Williams Hematology, 9th Edition Mc Graw Hill : Free Download, Borrow, and Streaming : Internet Archive

Williams Hematology 9th E

archive.org

@Nelson Vergel in case you are interested. Good review.

tareload · Jan 3, 2023

Increased cardiac output and microvascular blood flow during mild hemoconcentration in hamster window model | American Journal of Physiology-Heart and Circulatory Physiology

The effect of small hematocrit (Hct) increases on cardiac index (cardiac output/body wt) and oxygen release to the microcirculation was investigated in the awake hamster window chamber model by means of exchange transfusions of homologous packed red blood cells. Increasing Hct between 8 and 13%...

journals.physiology.org

Note well all you hard charging workout people:

Finally:

Hematocrit or Hemoglobin or RBC are incomplete measure of blood viscosity. Hct+plasma viscosity gives you a much better picture absent direct characterization of whole blood viscosity.