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

[TorontoTRT]

Reducing dose and increased my hematocrit.

 

[TorontoTRT]

Paradoxically the higher my rbc, hct and hg are the better I feel. Could it have anything to do with being tall and having a big frame / weight / muscle mass?

 

[S1W]

Reducing dose and increased my hematocrit.

Are you saying you made a significant reduction in dosage and saw your HCT increase? If so, how much of a dosage decrease and how long were you on this reduced dose protocol before you retested HCT?

 

[tareload]

Reducing dose and increased my hematocrit.

You'll have to figure out your appropriate tradeoff with your provider.

You mentioned your Hct went up 10% after starting TRT. You didn't add much detail above but I see you dropped your weekly dosage 20% and increased your frequency. Your Hct went up 2%. I have no reason to doubt your numbers. Automated cell counters are pretty precise (CI typically 1-2%). Water status at both blood draws?

You may need to drop your dosage more to see a drop in Hct. Have you checked your iron status? Some dudes are very sensitive to dosage. Glad you are feeling well and hope my posts help you understand more about Hct and blood viscosity and variability among people.

 

[TorontoTRT]

Dropping dose further would be pointless. At that dropped dosage of 40 mg every 3.5 days all trt benefits went away. Tried it for 7 weeks. Now trying 70 mg every 5 days. Seems like this one feels the best so far. Better then 100 mg every 7 days and better then 40 mg twice a week. The 40 mg twice a week protocol really was the worst. Acne tripled, hematocrit went up, libido and erections disappeared. After switching to 70 mg everything good returned. Acne went down again. So strange.

 

[S1W]

Dropping dose further would be pointless. At that dropped dosage of 40 mg every 3.5 days all trt benefits went away. Tried it for 7 weeks. Now trying 70 mg every 5 days. Seems like this one feels the best so far. Better then 100 mg every 7 days and better then 40 mg twice a week. The 40 mg twice a week protocol really was the worst. Acne tripled, hematocrit went up, libido and erections disappeared. After switching to 70 mg everything good returned. Acne went down again. So strange.

Interesting - thanks for sharing. What is your SHBG?

 

[TorontoTRT]

Around 30

 

[Vince Carter]

1. Platelets: Haven't gotten there yet. And thread so far is about concern of elevated Hct. Most discussions I hear immediately jump to clotting without consideration of how elevated Hct itself is pause for concern. Good to start first with the overlooked basics then add in complexity.

2. Other treatments: guess you missed post #15:


3. You jumped right to draining blood, wow that was fast. Other group that get's drained alot: Read up on hemochromatosis. To address your point, a much more elegant approach to handle Hct is to reduce the dose rather than bloodlet. This is a great segue into hemochromatosis and genetics...

So #1, dismiss Platelets because you don't want to go there. Noted.
#2, if HCT were controllable, with another drug...(don't make me laugh) this is just too funny.
and #3, as if a dose reduction no one has done that and/or increased frequency with smaller shots.

I see you're new here. You'd be very well served to stop posting and start reading, on the magnitude of about 10:1 how much you read and how much you post.

 

[tareload]

So #1, dismiss Platelets because you don't want to go there. Noted.
#2, if HCT were controllable, with another drug...(don't make me laugh) this is just too funny.
and #3, as if a dose reduction no one has done that and/or increased frequency with smaller shots.

I see you're new here. You'd be very well served to stop posting and start reading, on the magnitude of about 10:1 how much you read and how much you post.

Have you measured your hemochromatosis (HH) status? Transferrin saturation? There's a reasonable PCR test to check your HH status:

Labcorp HH DNA assay

You sound frustrated and I am empathetic to you. I hope you get the results you are looking for and I realize it can be a hard journey. I wish you peace and a life free from suffering.

I read your Dr. is Dr. Saya and he can discuss with you the many people that have had benefit from dose reduction. I benefited but of course mileage varies. I am on the journey just like you. If your iron regulation/metabolism is dysfunctional (as is the case with HH), your HgB and Hct will be very sensitive to TRT dosage and its effect on hepcidin:

Worth a consideration. Happy reading:
Hemochromatosis Unveiled by Testosterone Replacement in a Man with Hypogonadism

Testosterone Perturbs Systemic Iron Balance ThroughActivation of Epidermal Growth Factor ReceptorSignaling in the Liver and Repression of Hepcidin

Regulation of the Iron Homeostatic Hormone Hepcidin

Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells

 

[tareload]

Is your blood pressure creeping up over time? Don't want to just blindly take a blood pressure medication because you have high blood pressure. Do you care to find out what's causing your hypertension? Enjoy this nice case report. The trends may look familiar to some. Although some may suggest erythrocytosis (Hct > 52%) is benign, plethora of literature and basic physics would indicate otherwise.

I continue to be grateful for Dr Saya's comments about "balance". You've got to balance and determine the appropriate tradeoff of risk/reward for yourself.

Testosterone use causing erythrocytosis

 

[tareload]

I've seen a number of comments (even interviews with Experts) trying to rationalize running Hct high because there's plenty of people at high altitude that do just fine with high Hct. Truth is there are a fraction of these folks that suffer significant symptoms and they are a great group to study and see how excess blood viscosity manifests in increased cardiovascular risk:

High Blood Viscosity and Hemoglobin Concentration Contribute to Reduced Flow-Mediated Dilation in High-Altitude Excessive Erythrocytosis

Abstract

Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g/dL in adult males) is associated with increased cardiovascular risk in highlander Andeans. We sought to quantify shear stress and assess endothelial function via flow-mediated dilation (FMD) in male Andeans with and without EE. We hypothesized that FMD would be impaired in Andeans with EE after accounting for shear stress and that FMD would improve after isovolemic hemodilution. Brachial artery shear stress and FMD were assessed in 23 male Andeans without EE (age: 40±15 years [mean±SD]; Hb<21 g/dL) and 19 male Andeans with EE (age: 43±14 years; Hb≥21 g/dL) in Cerro de Pasco, Peru (4330 m). Shear stress was quantified from Duplex ultrasound measures of shear rate and blood viscosity. In a subset of participants (n=8), FMD was performed before and after isovolemic hemodilution with blood volume replaced by an equal volume of human serum albumin. Blood viscosity and Hb were 48% and 23% higher (both P<0.001) and FMD was 28% lower after adjusting for the shear stress stimulus (P=0.013) in Andeans with EE compared to those without. FMD was inversely correlated with blood viscosity (r2=0.303; P<0.001) and Hb (r2=0.230; P=0.001). Isovolemic hemodilution decreased blood viscosity by 30±10% and Hb by 14±5% (both P<0.001) and improved shear stress stimulus-adjusted FMD from 2.7±1.9% to 4.3±1.9% (P=0.022). Hyperviscosity, high Hb, or both, actively contribute to acutely reversible impairments in FMD in EE, suggesting that this plays a pathogenic role in the increased cardiovascular risk.​

Take a look at these plots:

Refresher on FMD:

Flow-mediated dilation

Now couple this information with my previous post on the same Hct values giving very different blood viscosity:

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

From the paper's discussion:

Blood viscosity elicits opposing resistive and shear stress-associated vasodilatory effects on hemodynamics.51,52 Modest increases in blood viscosity have been shown to reduce blood pressure via increased shear stress-associated NO formation but increasing viscosity >50% increased blood pressure.52 Moderate polycythemia may be associated with greater FMD in hypoxemic patients.53 However, the relationship between blood viscosity and Hb becomes steeper in Andeans with EE (Figure 1). Although the mechanisms that determine this relationship remain to be established (see below), endothelial dysfunction in instances of high levels of blood viscosity and Hb may render individuals especially susceptible to increased cardiovascular risk as both whole blood viscosity54,55 and reduced FMD56,57 predict cardiovascular risk and events.​

Enlarged brachial artery diameters have previously been reported in participants with EE,10 which appears to be a phenotypic characteristic of this maladaptive response to chronic hypoxemia. The large diameter may be the result of structural adaptations in response to high blood viscosity-associated shear stress, the so-called shear stress normalization hypothesis.58,59 Additionally, there may be a role for chronic hypoxemia in maintaining the conduit artery in a vasodilated state, supported by the observation that oxygen supplementation decreases brachial artery diameter in patients with CMS.10 Thus, enlarged conduit artery diameter is a fundamental component of EE pathophysiology. In non-EE populations, an inverse relationship between baseline diameter and FMD has been observed.60 This has been interpreted to suggest that the same endothelial function is reflected by a progressively smaller percent and absolute FMD response as baseline artery dimensions increase.60 However, FMD increased with hemodilution while baseline artery diameter did not change, providing support that the larger baseline diameters per se do not explain the impaired FMD in EE.​

We have identified a role for high Hb and blood viscosity in contributing to the reduced FMD in Andeans with EE. However, the mechanisms responsible for the low FMD in Andeans with EE are likely multifaceted and cannot be completely elucidated from the present study. For instance, increased systemic free radical formation has been reported in Andeans with EE compared to Andeans without,8,12 and this likely contributes to the lower FMD by chronically inactivating NO (oxidative-nitrosative stress).8,50 Additionally, cell-free Hb is a 1000-fold more potent NO scavenger61–64 than red blood cell Hb and can impair endothelium-dependent vasodilation.61,65 Polycythemic patients at sea level have elevated levels of cell-free Hb compared to healthy control participants, and polycythemic patients with hypertension have higher cell-free Hb compared to normotensive polycythemic patients.66 Thus, cell-free Hb may play a role in the NO scavenging and subsequent reduced FMD and increased cardiovascular risk in Andeans with EE.1 Further, measures of erythropoietin to soluble erythropoietin receptor (an erythropoietin antagonist) ratio may have provided additional mechanistic insight, as this ratio is increased in CMS67,68 and erythropoietin has been shown to impair endothelial function in humans.69 Therefore, future investigations should investigate markers of oxidative stress, NO bioavailability (in both plasma and red blood cell), cell-free Hb, and levels of erythropoietin to better dissect the mechanisms linking EE with reduced FMD and related adverse vascular outcomes.​

So if you've got autoimmune issues, high cRP, elevated plasma viscosity, probably a good idea not to run your Hct up too high! Also, there's no magic cutoff at a Hb of 21 g/dL. The plot of FMD vs blood viscosity is continuous and shows why cautious providers don't want to run Hct above 50-51%.

 

[TorontoTRT]

None of this matters. Testosterone INCREASES NO production and dilates blood vessels to account for any blood thickening essentially cancelling out any negative side effects. Hence no one on TRT us dropping dead. If this was not true, one would see an increase in blood pressure and heart rate due to thicker blood. From my personal experience over the years my vitals have not changed. Rating heart rate 59 bpm. Blood pressure 100/65. Hematocrit around 52-54. As high as 58.

 

[tareload]

None of this matters. Testosterone INCREASES NO production and dilates blood vessels to account for any blood thickening essentially cancelling out any negative side effects. Hence no one on TRT us dropping dead. If this was not true, one would see an increase in blood pressure and heart rate due to thicker blood. From my personal experience over the years my vitals have not changed. Rating heart rate 59 bpm. Blood pressure 100/65. Hematocrit around 52-54. As high as 58.

You mean "None of this matters to YOU." Unless your experience accurately represents all humans on this planet, your statement seems irresponsible. Especially after I have painstakingly shown that not all Hct values are created equal.

My response to an Hct of 52 is different that yours. Take a look:

https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP280141

Abstract

Key points

• Changes in hematocrit influence nitric oxide signalling through alterations in shear stress stimuli and hemoglobin scavenging of nitric oxide; these two regulatory factors have not been assessed simultaneously
• Isovolumic hemodilution led to a marked increase in brachial artery flow‐mediated dilation in humans
• The increase in flow‐mediated dilation occurred in the face of an unaltered shear stress stimulus for vasodilation and reduced resting steady‐state nitric oxide levels in the blood
• Collectively, our data point towards hemoglobin scavenging of nitric oxide as a key regulatory factor of brachial flow‐mediated dilation and highlight the importance of simultaneous consideration of nitric oxide production and inactivation when investigating vascular function in humans

Abstract
Hemoglobin (Hb) may impact the transduction of endothelium‐dependent and nitric oxide (NO) mediated vasodilator activity, given its contribution to shear stress stimuli and diverse biochemical reactions with NO. We hypothesized that an acute reduction in [Hb] and hematocrit (Hct) would increase brachial artery flow‐mediated dilation (FMD). In eleven healthy males (28 ± 7 years; 23 ± 2 kg m−2), FMD (Duplex ultrasound), arterial blood gases, Hct and [Hb], blood viscosity, and NO metabolites (ozone‐based chemiluminescence) were measured before and after isovolumic hemodilution, where ∼20% of whole blood was removed and replaced with 5% human serum albumin. Hemodilution reduced Hct by 18 ± 2% (P < 0.001) and whole blood viscosity by 22 ± 5% (P < 0.001). Plasma nitrite (P = 0.01), S‐nitrosothiols (P = 0.03), and total red blood cell NO (P = 0.001) were collectively reduced by ∼15–40%. Brachial artery FMD increased by ∼160% from 3.8 ± 2.1 to 9.7 ± 4.5% (P = 0.004). Statistical covariation for the shear stress stimulus did not alter FMD, indicating that the increase in FMD was not directly related to alterations in whole blood viscosity and the shear stimulus. Collectively, these findings indicate that hemoglobin scavenging of NO appears to be an important factor in the regulation of FMD under normal conditions through constraint of endothelium‐dependent NO‐mediated vasodilation in healthy humans.


Hot off the press. Evidently, these researchers didn't get your memo. I am glad you don't suffer elevated BP and reduced FMD with increased Hct.

 

[TorontoTRT]

Read the testosterone impact on Nitric oxide production. If high hct was bad for guys on trt imagine how many guys would drop dead? I agree most people can react differently but the testosterone pharmacology is the same in everyone.

 

[tareload]

Read the testosterone impact on Nitric oxide production. If high hct was bad for guys on trt imagine how many guys would drop dead? I agree most people can react differently but the testosterone pharmacology is the same in everyone.

You've got some false dilemma and circular reasoning fallacy going on here.

So with this logic, there's no concern with competing effects since testosterone increases NO production, end of story. You can run your Hct as high as you want with impunity since testosterone will increase NO production. So why is it some men see a >20-30 point increase in systolic BP with their Hct rising from 45 to 54%? Everyone has your cardiovascular response to TRT?

If raising Hct with TRT is bad for guys, then we'd be seeing them dropping dead. So if we don't observe them "dropping dead", then no problem with elevated Hct.

Interesting.

Watch from 46:30 till the end:
Testosterone and Estrogen in Men: Good, Bad or Indifferent?

As Dr. Rouzier mentions, men observed at high alititude suffering (i.i., side effects) from excessive erythrocytosis (EE) already have significantly higher testosterone levels than those that don't have EE. He uses this to justify TRT induced erythrocytosis since it's testosterone mediated and these guys aren't "dropping dead".

Your claim is that use of exogenous testosterone should cancel out any and all increase in viscosity due to increased Hct from the testosterone? So should we give these guys with EE at high altitude more testosterone? They must not be making enough. They need more? Or is it that they need exogenous testosterone since their endogenous testosterone (which is already high compared to control population) is not high enough?

Take a read:
High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men

I've read over and over the claim that people at altitude have high Hct and they are fine. They aren't "dropping dead". Therefore, guys with high Hct from TRT are fine. I took the time to post some recent mechanistic study of why running Hct up too high can be problematic and posted before why all Hct values are not created equal (marked variation in blood viscosity vs Hct depending on plasma viscosity status).

So if you don't want to read, that's up to you. But for others trying to make sense of all this, the concern I am trying to daylight is not an acute event, "dropping dead", or even clotting issue leading to stroke. It's long term wear and tear on the heart leading to early failure. When you die prematurely from heart failure there may be no one there pointing out "see, he ran his Hct too high for 10 years."

I summed this up in a thread on another forum (edited for length):

Benefits of Estrogen for TRT Patients
The primary concern with elevated blood viscosity is hypertension, increased shear stress to the lumen (I’m sure you are familiar with what that does), and risk of ischemia and reduced perfusion for compromised patients / older patients. Also, what’s the concern with young person running high blood viscosity for years? Ask AAS abusers what the long term implications of elevated Hct are? Integrate out over 20 years the cost of making your heart do extra, measurably more work. Combine that with a patient who has limited vasodilation ability.

So according to this logic, no worries with elevating serum viscosity, just let it ride? For a patient with plenty of mileage on the heart, pre-CHF or CHF, no worries with cranking up the blood viscosity? Harmless?

This response is lazy and avoids having to discuss the fact the heart is a pump and a pump is designed to operate on a pump curve (just to keep it simple). Depending on the viscosity of the fluid the pump is pumping, you will land on a point on that curve. Surely you understand the long term implications of running a pump too high on the gpm vs hp curve? Any concerns for long term issues if you want that pump in service for a while? We aint talking about a pump in a manufacturing facility that can be replaced rather easily. We are talking about a heart.

For folks who talk about optimization, you seem to not understand or ignore the penalty function associated with performance vs longevity. For readers, I’ve shared what I think is important for you to consider. Take care of your cardiovascular system. That means use reasonable caution. Running your Hct above 50, or even 55 is not that. But given the TT levels you guys are recommending, I can see how this little inconvenience causes an issue. Elevated Hct has to be harmless in your practice otherwise you have to have your patients doing an oil drain on a regular, painful basis.

 

[tareload]

@TorontoTRT, help me understand how TRT would fundamentally shift the qualitative shape of the curves attached below? In order for testosterone to counteract any and all increase in blood viscosity via increased hematocrit, it would have to remove inflection point below on the plots of peak NO vs hematocrit:

The Effect of Small Changes in Hematocrit on Nitric Oxide Transport in Arterioles

Figures 9 and and1010 explore this behavior in detail. Figure 9 shows the relationship between peak CNO and systemic Hct for several values of the exponent m in the constitutive equation [24]. For m = 5 used in the simulations presented in Figure 8 (and other values of m as small as 2), the CNO-Hct relationship exhibits an inflection point, at which CNO reaches its maximum and then starts to decrease. This is due to the asymptotic behavior of RNO,max (see the constitutive equation [24] and/or Figure 3a). In this limit, further increases in shear stress (and Hct) do not affect NO production and the increased consumption of NO by RBCs is no longer compensated by increasing shear-induced NO production, thus causing NO availability to decrease beyond the inflection point. The exponent m in the constitutive equation [24] determines its steepness and, hence, the rate at which NO production varies with shear stress. Larger values of the parameter m correspond to a steeper increase in NO production with shear stress and, hence, to a sharper increase in NO availability with rising Hct. Figure 10 confirms that this behavior remains essentially the same for different values of the glycocalyx thickness (in these simulations we set m = 5).

The following mechanisms combine to produce the nonlinear relationship between CNO and Hct.

1. The rate of NO consumption by the RBC core increases with Hct.
2. Blood viscosity and shear stress at the vessel wall increase with Hct.
3. O2 availability and NO production rates increase with Hct (equation [7]).
4. The thickness of the plasma layer decreases and shear stress increases with Hct (equation [16]).
5. The distance NO must diffuse before being consumed by RBCs in the core decreases with Hct.

Effects 2, 3, and 4 cause NO availability to increase, whereas effects 1 and 5 have the opposite effect. Interaction of these competing effects results in the behavior shown in Figures 9 and and10.10. It is worthwhile emphasizing that changes in the relative strengths of any of these phenomena may have quantitative and qualitative effects on the final relationship between NO availability in the vascular wall and systemic Hct.

Comments @RobRoy? Review on your podcast?

 

[tareload]

Managing Hct when you are on the fine line between TRT and *pFRT (mild cycle, supra, whatever you want to call it). Go too high it won't matter. But in the very fine gray zone at high end of physiologic range, perhaps more infrequent injections will help if you are using injectable testosterone esters (weekly instead of daily):

Start here and read down. I'd love to hear other's feedback/criticism on the topic.

What is TRT and What is NOT TRT

Note: I originally posted this over at T-Nation so hope it's ok if I share it here @Nelson Vergel. Had an interesting and lively exchange over there with one of the proponents of the "TOT" protocol (Testosterone Optimization Therapy as it is called). This short summary gives guys a look of...

www.excelmale.com

 

[Nelson Vergel]

This might sound crazy but the higher the hematocrit the better I feel.

How high has your hematocrit gone and for how long? What's your BMI? Just curious.

 

[tareload]

@readalot It's so good to see a chemical engineer that remembers his fluid dynamics (unlike me)

Thank you Sir. I truly do admire your endurance and service in helping people. Truly amazing.

 

[Match]

Aqui ocorre em contrário. Meu Hematócrito sempre ao meio no limite inferior - 40, 41 - mesmo com Testosterona mais ou menos normal - 637 ng / dl.
O que fazer pra aumentar o HCT?