Managed hematocrit but not hemoglobin?

[Belekas]

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 to ride till the wheels fall off, or I got him wrong? I was 3 years on 250mg test-e, doing heavy resistance training 5-6x/week, eating tons of food, doing tons of cardio and my HC was around 52% at max without no blood donations fwiw. Now with all the info you experienced guys post here this is a contradiction so I'm very interested here as he's a real doc that has a lot of patients as I assume. Ofc I don't know for sure as I haven't done my research on him but if thats the case then what he is doing ain't looking to be the healthiest option? My thinking would be if all numbers look good, BP looks pretty, etc, for now, that doesn't mean they will look the same or not worse in year or years time and that might do some or serious damage by that time.

 

[Blackhawk]

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 to ride till the wheels fall off, or I got him wrong? I was 3 years on 250mg test-e, doing heavy resistance training 5-6x/week, eating tons of food, doing tons of cardio and my HC was around 52% at max without no blood donations fwiw. Now with all the info you experienced guys post here this is a contradiction so I'm very interested here as he's a real doc that has a lot of patients as I assume. Ofc I don't know for sure as I haven't done my research on him but if thats the case then what he is doing ain't looking to be the healthiest option? My thinking would be if all numbers look good, BP looks pretty, etc, for now, that doesn't mean they will look the same or not worse in year or years time and that might do some or serious damage by that time.

Where is ANY actual clinical data that shows HCT 60% is fine and safe?

 

[Belekas]

Where is ANY actual clinical data that shows HCT 60% is fine and safe?

I'm interested in that as well. He said "I can find no evidence that elevated HCT SOLELY due to TRT is an “issue”. "If someone has persistent HCT of 60 or Hb over 20 then I recommend they have a full workout for sleep apnea or any other contributing issue.
Even one of our local hematologists doesn’t “freak out” until Hb over 20." Copy, paste from our short chat.

 

[Systemlord]

Where is ANY actual clinical data that shows HCT 60% is fine and safe?

There’s a study out there on mice who were genetically altered and hematocrit at 83% and no circulatory problems, active and healthy.

 

[Blackhawk]

There’s a study out there on mice who were genetically altered and hematocrit at 83% and no circulatory problems, active and healthy.

LOL!

 

[Systemlord]

There’s a study out there on mice who were genetically altered and hematocrit at 83% and no circulatory problems, active and healthy.

LOL!

Really, no drugs or heroin and no I didn’t hit my head. These links should take some of the humor out of my post and inject some level of seriousness.

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis - PubMed

We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs...

pubmed.ncbi.nlm.nih.gov

If you‘ve got the time, I employ you to watch the video in it’s entirety.

Enjoy-> 21:15

 

[madman]

I'm interested in that as well. He said "I can find no evidence that elevated HCT SOLELY due to TRT is an “issue”. "If someone has persistent HCT of 60 or Hb over 20 then I recommend they have a full workout for sleep apnea or any other contributing issue.
Even one of our local hematologists doesn’t “freak out” until Hb over 20." Copy, paste from our short chat.

The results from the TRAVERSE study which will be released in early 2023 should help clear some of this up!

Although the sad fact of the matter is are we really going to be any better off?

1.62% Androgel!



Study Design: The Testosterone Replacement Therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study is a randomized, double-blind, placebo-controlled, parallel-group, non-inferiority, multicenter study. Eligible participants are men, 45 to 80 years, with serum testosterone concentration <300 ng/dL and hypogonadal symptoms, who have evidence of pre-existing CV disease or increased risk of CV disease. Approximately 6,000 subjects will be randomized to either 1.62% transdermal testosterone gel or a matching placebo gel daily for an anticipated duration of up to 5 years. The primary outcome is CV safety defined by the major adverse CV event (MACE) composite of nonfatal myocardial infarction, nonfatal stroke, or death due to CV causes. The trial will continue until at least 256 adjudicated MACE endpoints have occurred to assess whether the 95% (2- sided) upper confidence limit for a hazard ratio of 1.5 can be ruled out. Secondary endpoints include prostate safety defined as the incidence of adjudicated high-grade prostate cancer and efficacy in domains of sexual function, bone fractures, depression, anemia, and diabetes. As of July 1, 2021, 5,076 subjects had been randomized.



Take-home points

*the clinical significance of a hematocrit >54% is unknown

*Although it is not yet clear what upper limit of hematocrit level is clinically desirable, dose adjustments may be necessary to keep hematocrit below 52–54%

*There are conflicting reports in the literature regarding the association between secondary erythrocytosis and MACE and VTE. This conflicting evidence in part contributes to the varying definitions of what is a “high” hematocrit while on TT

*Despite this, the evidence for secondary polycythemia causing harm during TT is scarce, and the hematocrit-based cutoffs present in multiple guidelines appear to be arbitrarily chosen

*The Endocrine Society uses a hematocrit threshold of >50% as a relative contraindication to initiating TT and >54% as an indication to discontinue treatment [1]. The European Association of Urology (EAU) guidelines on hypogonadism also state that the hematocrit should not exceed 54%, while recent Canadian guidelines cite 55% as the safe upper limit [15, 40]. The AUA guidelines on testosterone deficiency define polycythemia as a hematocrit of 52% and recommend stopping or reducing treatment if the hematocrit reaches 54% [14]

*The upper limit of normal for hematocrit in most laboratory reference ranges in healthy adult males is 54%, which is where this value is likely derived

*The major limitation to using these studies is that they involve population sampling, and do not investigate men on testosterone. Regardless, a hematocrit of ≥54% appears to be the consistent threshold to discontinuing or reducing treatment utilized by major urologic governing bodies, while the evidence for this specific cutoff is lacking

*Phlebotomy is effective in the management of erythrocytosis in patients with PV in reducing thromboembolic events and this benefit may be conferred onto patients with secondary erythrocytosis secondary to TT, though there is no high-quality evidence to support this claim

Management of Erythrocytosis in Men Receiving TRT

Management of Erythrocytosis in Men Receiving Testosterone Therapy: Clinical Consultation Guide (2022) Pranjal Agrawal, Sajya M. Singh, Taylor Kohn 1. Introduction Testosterone deficiency, previously known as male hypogonadism, affects approximately 25% of all men, with a prevalence that...

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post #4

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...

www.excelmale.com

*Despite this, the evidence for secondary polycythemia causing harm during TT is scarce, and the hematocrit-based cutoffs present in multiple guidelines appear to be arbitrarily chosen

*Polycythemia and erythrocytosis have been used interchangeably, though polycythemia implies an increase in all blood cells and so erythrocytosis is more accurate when describing the increased erythrocyte mass related to TT [13]. Erythrocytosis confers an increased blood viscosity and concerns arise from the potential increased risk of thromboembolic events including myocardial infarction and cerebrovascular accidents

*Amongst randomized controlled trials (RCTs), meta-analyses do not support an increased risk of MACE; however, these trials are not designed to detect MACE as their primary outcome and are often underpowered to do so. Unfortunately, none of these aforementioned trials evaluated secondary polycythemia as a potential independent risk factor for these adverse events. Amongst multiple guidelines currently, polycythemia is grounds for TT cessation or modification, without evidence that this actually increases the risk

*Another treatment option includes phlebotomy though the benefits of this practice are not clear in men with secondary erythrocytosis from TT

*Polycythemia can be divided into primary and secondary according to its etiology. Primary polycythemia, also known as polycythemia vera (PCV), is due to an over-production of erythrocytes secondary to intrinsic cellular defects within the bone marrow. PCV is often due to a mutation in JAK2, a tyrosine kinase, leading to the proliferation of erythrocytes independent of cellular control

*The secondary subtype is due to either a physiological response to decreased tissue oxygenation or from inappropriate stimulation of erythropoiesis, such as with TT [18]

*The mechanism behind secondary erythrocytosis from TT is multifactorial

*The marked decrease in hepcidin is hypothesized to increase iron metabolism, systemic absorption of iron, and erythropoiesis

*Another mechanism behind secondary polycythemia involves erythropoietin (EPO) [21]. Cellular hypoxia stimulates EPO, a renal cytokine, causing an increase in red blood cell production directly in the bone marrow

*EPO levels failed to decline after subsequent hemoglobin rises, demonstrating the possibility for uninhibited stimulation

*Estradiol, a breakdown product of testosterone via aromatase, may also play a role in polycythemia

*The increase in estradiol via increased aromatization in men on TT may increase telomerase activity, resulting in increased hematopoietic stem cell proliferation and survival [23]

*OSA by itself is believed to cause erythrocytosis via hypoxemia [25]. Combined with TT, it is possible that the effects on erythrocytosis may be compounded, either through higher metabolic requirements with elevated testosterone, changes in response to hypoxia, and physiologic changes to the airways

*Erythrocytosis can lead to increased blood viscosity [27, 28]. At the molecular level, it has been shown to impact platelet adhesiveness and bleeding time [29]. Elevated hematocrit levels can also increase thromboxane A2 concentrations thereby activating new platelets and increasing platelet aggregation [16]

*Patients with obstructive sleep apnea, advanced age, obesity, type II diabetes mellitus, elevated baseline hematocrit (>50%), and those who live in high altitudes are at higher risk of developing erythrocytosis after TT [32]

*Testosterone formulation, dose, and pharmacokinetics collectively determine the risk of erythrocytosis [11]. The general hypothesis is that increased duration in supraphysiological testosterone levels results in an increased risk of erythrocytosis

*Secondary erythrocytosis is a predictable side effect of testosterone replacement therapy with objective increases in hematocrit noted after one month of therapy

*The percentage increase in hematocrit continues to increase in a linear dose-dependent fashion [38]. Side effects of secondary erythrocytosis resulting from hyperviscosity include paresthesias, blurred vision, fatigue, and headaches [39]

*There are conflicting reports in the literature regarding the association between secondary erythrocytosis and MACE and VTE. This conflicting evidence in part contributes to the varying definitions of what is a “high” hematocrit while on TT

*The Endocrine Society uses a hematocrit threshold of >50% as a relative contraindication to initiating TT and >54% as an indication to discontinue treatment [1]. The European Association of Urology (EAU) guidelines on hypogonadism also state that the hematocrit should not exceed 54%, while recent Canadian guidelines cite 55% as the safe upper limit [15, 40]. The AUA guidelines on testosterone deficiency define polycythemia as a hematocrit of 52% and recommend stopping or reducing treatment if the hematocrit reaches 54% [14]

*The upper limit of normal for hematocrit in most laboratory reference ranges in healthy adult males is 54%, which is where this value is likely derived

*The major limitation to using these studies is that they involve population sampling, and do not investigate men on testosterone. Regardless, a hematocrit of ≥54% appears to be the consistent threshold to discontinuing or reducing treatment utilized by major urologic governing bodies, while the evidence for this specific cutoff is lacking

*In a meta-analysis of all randomized controlled trials for TT and cardiovascular risk by Corona et al., they concluded that the existing evidence does not support a causal role between TT and adverse CV events when hypogonadism is appropriately diagnosed and treated [45]. While there is no convincing evidence that links polycythemia in patients who are on TT and MACE, physicians should be prepared to discuss the risks with their patients in a shared-decision making approach

*Therapeutic phlebotomy is one way in which patients may “treat” erythrocytosis. Phlebotomy is a mainstay of treatment in PCV and there are no absolute contraindications [48]

*Phlebotomy is effective in the management of erythrocytosis in patients with PV in reducing thromboembolic events and this benefit may be conferred onto patients with secondary erythrocytosis secondary to TT, though there is no high-quality evidence to support this claim

*There are no evidence-based guidelines that outline the frequency or volume of phlebotomy protocols in patients receiving TT

*Whether or not phlebotomy has a role to play in the management of secondary polycythemia deserves further study

*At this point, phlebotomy appears to be a safe approach to reducing hematocrit but physicians should be aware that it may not be sufficient in reducing hematocrit levels on a long-term basis

 

[Blackhawk]

I'm interested in that as well. He said "I can find no evidence that elevated HCT SOLELY due to TRT is an “issue”. "If someone has persistent HCT of 60 or Hb over 20 then I recommend they have a full workout for sleep apnea or any other contributing issue.
Even one of our local hematologists doesn’t “freak out” until Hb over 20." Copy, paste from our short chat.

Really, no drugs or heroin and no I didn’t hit my head. These links should take some of the humor out of my post and inject some level of seriousness.

Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis - PubMed

We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs...

pubmed.ncbi.nlm.nih.gov

If you‘ve got the time, I employ you to watch the video in it’s entirety.

Enjoy-> 21:15

I wasn't laughing AT you! Just at the information. I still am. I am not going to base my own care decisions on mouse study trivia, nor Wiggins/Campbell's presentation. They take off from that study as reference and then state that no one is at risk below 55%. Sorry, I've had high hematocrit and become symptomatic at 52%.

If this mouse research leads to genetic modifications that can be performed on us to thrive with 83% hematocrit, I am all for it.

 

[Systemlord]

I am not going to base my own care decisions on mouse study trivia, nor Wiggins/Campbell's presentation.

Neither am I because that would be foolish.

 

[tareload]

the clinical significance of a hematocrit >54% is unknown

Why would using Hct as the primary study effect be very challenging?

Hint:

Almost no one pays attention to plasma viscosity or whole blood viscosity. Hct only part of the total picture.


I should just put this one in my signature for efficiency:

Plasma viscosity: a forgotten variable - PubMed

Evaluation of plasma viscosity has been underutilized in the clinical practice. Plasma viscosity is determined by water-content and macromolecular components. Plasma is a highly concentrated protein solution, therefore weak protein-protein interactions can play a role that is not characterized...

pubmed.ncbi.nlm.nih.gov

Another:

Blood viscosity as a forgotten factor and its effect on pulmonary flow

The effect of smoking on blood viscosity is widely known. There are, however, few studies on the effect of blood viscosity on pulmonary circulation.We aimed to observe the relationship between blood viscosity and pulmonary circulation among smokers and ...

www.ncbi.nlm.nih.gov

Study up guys if you want to get a better picture. 52 or 54% Hct means very different clinical picture depending on the patient.

Whole Blood Viscosity and Cardiovascular Diseases: A Forgotten Old Player of the Game

www.ncbi.nlm.nih.gov

 

[tareload]

More...

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

Hi ExcelMale folks, I wanted to start off by expressing my gratitude for this site, all of the amazing work that has been put in to make this place such a great source of information. I would expect no less from a chemical engineer :). I've been following this "debate" about how to properly...

www.excelmale.com

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...

www.excelmale.com

If you have a Doc that understands and appreciates the above like Dr. Saya you are fortunate indeed.

 

[M.J]

Normally symptoms of high hemoglobin is high blood pressure, headaches, fatigue, abdominal pain and rarely vision changes.

High estrogen cause increase the amount of water retention leading to stiff joints, the exact opposite of low estrogen.

You’re barking up in the wrong tree with this idea your “normal blood parameters“ is causing stiff joints. You become a little dehydrated after donating, the loss of water may lessen your fluid retention in your joints, but it is a bandaid solution and ill advised.

My endocrinologist just contacted me, tells me he talked at length to a hematologist about my monthly phlebotomies and says there are no longer necessary.

My last hemoglobin was 18.4 and hematocrit 53%, both are above normal.

So you suggest 17 somthinghemoglobin is fine ? Cuz my doc was against it.

 

[M.J]

Honestly even with all this action and blood test I am not there yet still struggling with libido. Make you think if trt is worth all this.
One good thing about trt is I still have hope to find something that work with all this testosterone and hcg.

I really wish if it’s was that straight forward.

 

[NeverSayNeverAgain]

@M.J



I recommend getting a capillary HB tester and just monitor that way Im gonna vouch for the Hemocue 201HB or the BioAid HB tester because the microcuvettes are cheap. From there you monitor how much it fluctuates with creams and gels is will be a lot because its aligned with your T levels injections not so much and more on hydration. Iron levels fluctuate more than blood sugar does so just keep that in mind. You will probably be the highest in the morning when your the most dehydrated and lower at night because you are the most hydrated and T levels are at there lowest.

 

[Systemlord]

Stroke-Related Mortality at Different Altitudes: A 17-Year Nationwide Population-Based Analysis From Ecuador

Introduction: Worldwide, more than 5.7% of the population reside above 1,500 m of elevation. It has been hypothesized that acute short-term hypoxia exposure could increase the risk of developing a stroke. Studies assessing the effect of altitude on stroke ...

www.ncbi.nlm.nih.gov

 

[tareload]

Stroke-Related Mortality at Different Altitudes: A 17-Year Nationwide Population-Based Analysis From Ecuador.

Living at higher elevation with higher hematocrit may decrease cardiovascular risk! https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525493/...

www.excelmale.com