Newish Study on HCT

[GreenMachineX]

Has anyone seen this? It looks like those with higher hct lived longer...

https://www.liebertpub.com/doi/10.1089/andro.2021.0019

Testosterone Therapy: Increase in Hematocrit is Associated with Decreased Mortality​

"Results: HCT increased significantly (median change at final assessment: +5.0%) in men on TTh. HCT was higher (p = 0.021, rank-sum test) in those alive than in those who died, although median values were identical (49.0%). Baseline HCT and Δ HCT were inversely associated with mortality after adjustment for age in both logistic and Cox regression models. Men with final HCT >49.0% (median) suffered lower mortality than men with HCT ≤49.0%.

Conclusions: A median HCT increase of 5.0% was associated with TTh, mostly within 48 months of commencing therapy. An increase in HCT (up to 52.0% at final assessment) was independently associated with reduced mortality, indicating current guidelines using a HCT value of 54.0% as a threshold for management change are appropriate until further study."

 

[Nelson Vergel]

Thanks for sharing.

"
However, concerns remain regarding the safety of TTh. Although most studies demonstrate benefit or no change in cardiovascular disease (CVD), a few have reported higher CVD in men prescribed TTh.14–17 An explanation for these discrepant findings is that the population of men with adult-onset TD is heterogeneous18; thus, subgroups with different lifestyles, genetic, and environmental factors may influence clinical outcomes. Hematocrit (HCT) is a possible candidate in determining outcome as an increase in this variable is the commonest effect of TTh.19–21 Different guidelines have set varying HCT percentage thresholds above which they recommend withholding/discontinuing TTh and/or phlebotomy. For example, the British Society of Sexual Medicine,4 Endocrine Society,22 American Urological Association,23 and European Association of Urology24 have all adopted a threshold of 54%. The International Society for the Study of the Aging Male has adopted an HCT threshold of 52%,25 whereas the International Consultation for Sexual Medicine26 has recommended an even more conservative HCT threshold of just 50%.

HCT levels have been associated with changes in morbidity and mortality, although findings vary.19 A meta-analysis of 16 studies has shown that the highest HCT tertile (>0.463) was associated with increased CVD compared with the lowest tertile (<0.417).27 Similarly, in the Framingham cohort (of >34 years follow-up), the highest HCT quintile was associated with increased CVD as well as all-cause mortality.28 However, the European Prospective Investigation into Cancer and Nutrition-Netherlands study found no difference in CVD between the tertile distributions (>0.47 vs. <0.45) in CVD-free individuals.29 In the Scottish Heart Health Extended Cohort Study, HCT (mean ± SD: 0.4381 ± 0.0394) was significantly associated with CVD events and mortality, although this association was lost when the analysis was adjusted for the following confounders: lipids, blood pressure (BP), diabetes, smoking status, family history of CVD, and fibrinogen.30

Boffetta et al. suggested that this lack of consensus may result from a nonlinear relationship between HCT, CVD, and mortality.31 Thus, a U-shaped relationship between categories of HCT and mortality was found in Iranian adults of both genders, with low and high HCT values associated with increased overall mortality.31 Locatelli et al. found, after erythropoietin therapy in patients with end-stage renal disease and low baseline HCT (0.301 ± 0.045), that mortality was inversely proportional to the increase in HCT, also suggesting that the association between morbidity/mortality and HCT is nonlinear.32

The clinical impact of increased HCT during TTh requires further understanding. In this study, we report baseline characteristics of the men prescribed/not prescribed TTh and compare changes in HCT (intra- and intergroup), though our focus is primarily on men prescribed TTh. This is because of the current uncertainty regarding clinical outcomes associated with change in HCT after TTh. We studied the relationship between HCT and all-cause mortality in men on TTh. HCT is associated with hemoglobin (Hb) level33,34 and BP,35–37 both of which are predictors of mortality.38–42 Hence, these and other established risk factors such as waist circumference (WC), HbA1c, total cholesterol (TC), and triglycerides (TG) at the final assessment were included (if found to be significantly associated with mortality) as confounding variables."


Results:

The median hematocrit was 49 on TRT (testosterone undecanoate. Not sure if oral or injectable).
These men also had good blood pressure values. I am not sure this is what I see in most men using T injections. They usually have hematocrit over 53 and higher blood pressure.

 

[GreenMachineX]

Thanks for sharing.

"
However, concerns remain regarding the safety of TTh. Although most studies demonstrate benefit or no change in cardiovascular disease (CVD), a few have reported higher CVD in men prescribed TTh.14–17 An explanation for these discrepant findings is that the population of men with adult-onset TD is heterogeneous18; thus, subgroups with different lifestyles, genetic, and environmental factors may influence clinical outcomes. Hematocrit (HCT) is a possible candidate in determining outcome as an increase in this variable is the commonest effect of TTh.19–21 Different guidelines have set varying HCT percentage thresholds above which they recommend withholding/discontinuing TTh and/or phlebotomy. For example, the British Society of Sexual Medicine,4 Endocrine Society,22 American Urological Association,23 and European Association of Urology24 have all adopted a threshold of 54%. The International Society for the Study of the Aging Male has adopted an HCT threshold of 52%,25 whereas the International Consultation for Sexual Medicine26 has recommended an even more conservative HCT threshold of just 50%.

HCT levels have been associated with changes in morbidity and mortality, although findings vary.19 A meta-analysis of 16 studies has shown that the highest HCT tertile (>0.463) was associated with increased CVD compared with the lowest tertile (<0.417).27 Similarly, in the Framingham cohort (of >34 years follow-up), the highest HCT quintile was associated with increased CVD as well as all-cause mortality.28 However, the European Prospective Investigation into Cancer and Nutrition-Netherlands study found no difference in CVD between the tertile distributions (>0.47 vs. <0.45) in CVD-free individuals.29 In the Scottish Heart Health Extended Cohort Study, HCT (mean ± SD: 0.4381 ± 0.0394) was significantly associated with CVD events and mortality, although this association was lost when the analysis was adjusted for the following confounders: lipids, blood pressure (BP), diabetes, smoking status, family history of CVD, and fibrinogen.30

Boffetta et al. suggested that this lack of consensus may result from a nonlinear relationship between HCT, CVD, and mortality.31 Thus, a U-shaped relationship between categories of HCT and mortality was found in Iranian adults of both genders, with low and high HCT values associated with increased overall mortality.31 Locatelli et al. found, after erythropoietin therapy in patients with end-stage renal disease and low baseline HCT (0.301 ± 0.045), that mortality was inversely proportional to the increase in HCT, also suggesting that the association between morbidity/mortality and HCT is nonlinear.32

The clinical impact of increased HCT during TTh requires further understanding. In this study, we report baseline characteristics of the men prescribed/not prescribed TTh and compare changes in HCT (intra- and intergroup), though our focus is primarily on men prescribed TTh. This is because of the current uncertainty regarding clinical outcomes associated with change in HCT after TTh. We studied the relationship between HCT and all-cause mortality in men on TTh. HCT is associated with hemoglobin (Hb) level33,34 and BP,35–37 both of which are predictors of mortality.38–42 Hence, these and other established risk factors such as waist circumference (WC), HbA1c, total cholesterol (TC), and triglycerides (TG) at the final assessment were included (if found to be significantly associated with mortality) as confounding variables."


Results:

The median hematocrit was 49 on TRT (testosterone undecanoate. Not sure if oral or injectable).
These men also had good blood pressure values. I am not sure this is what I see in most men using T injections. They usually have hematocrit over 53 and higher blood pressure.

You're saying that the combination of high blood pressure and higher hct is likely the issue, but elevated hct with normal blood pressure may not increase risk?

 

[Nelson Vergel]

You're saying that the combination of high blood pressure and higher hct is likely the issue, but elevated hct with normal blood pressure may not increase risk?

I think increased blood pressure while on TRT may be an indication of high hematocrit and/or water retention.

I am saying that:

1- The conclusions from this study may not apply to many guys on TRT injections since:

• the median hematocrit was 49
• most had normal blood pressure

 

[Nelson Vergel]

They don't mention the injection protocol but I bet it is

Nebido, 1000 mg, every 12 weeks.

This protocol usually produces Total T levels under 550 ng/dL, much lower than what most guys on ExcelMale run.

 

[GreenMachineX]

I think increased blood pressure while on TRT may be an indication of high hematocrit and/or water retention.

I am saying that:

1- The conclusions from this study may not apply to many guys on TRT injections since:

• the median hematocrit was 49
• most had normal blood pressure

I've been noticing increased water retention from this daily protocol, but, oddly my blood pressure is still the best I've ever had, even better than when I was 19 joining the Army. I wonder in my case if the bloat is actually beneficial e2 conversion since I've struggled with low e2 for most of TRT. Nevertheless, I hope data keeps coming out with regard to safe hematocrit numbers.

My own doctor said he's OK with my hgb above 18 and hct around 55. His rationale based on hemotologists he's talked to is that hct is only problematic when it's from a disease state such as smoking, but not when it's from normal physiological response such as in living at altitude or TRT. I personally am not comfortable with those numbers though lol.

 

[Nelson Vergel]

My own doctor said he's OK with my hgb above 18 and hct around 55

I don't think these numbers will kill anyone in the long range. But I have seen hematocrit in some guys run as high as 63.

 

[GreenMachineX]

I don't think these numbers will kill anyone in the long range. But I have seen hematocrit in some guys run as high as 63.

Wait, you don't think 55 and 18 will cause damage long term???

 

[K.pietera]

I am on TRT for almost 4 years right now (20% transcrotal cream ) and the first two years my hematocrit or hemoglobin was still i range. The third year Hct spiked to 51% and Hgb to 18. I felt good but when I saw that on paper I freaked out and went to donate blood. It was good for 8 months and then the same results came up.

Now I have good blood pressure and I feel good so I think I will see within a few months from now what my levels will do because I read a lot of different things about it and as long as I feel good ( don't have headache,high blood pressure etc... ) I don't think I have to worry to much.

I have to stop freaking out when I see something is just above the 'normal' ranges because what is 'normal' ? Normal is not OPTIMAL I guess.

 

[GreenMachineX]

I am on TRT for almost 4 years right now (20% transcrotal cream ) and the first two years my hematocrit or hemoglobin was still i range. The third year Hct spiked to 51% and Hgb to 18. I felt good but when I saw that on paper I freaked out and went to donate blood. It was good for 8 months and then the same results came up.

Now I have good blood pressure and I feel good so I think I will see within a few months from now what my levels will do because I read a lot of different things about it and as long as I feel good ( don't have headache,high blood pressure etc... ) I don't think I have to worry to much.

I have to stop freaking out when I see something is just above the 'normal' ranges because what is 'normal' ? Normal is not OPTIMAL I guess.

I freak out too, but not with those numbers. 18 5 and 53 get to me though...

 

[K.pietera]

I freak out too, but not with those numbers. 18 5 and 53 get to me though...

Yes I understand that but how do you feel when you have those numbers ? you feel bad ?

 

[GreenMachineX]

Yes I understand that but how do you feel when you have those numbers ? you feel bad ?

Nope. The only time I felt off from hct was when it was 58 and I got dizzy from carnival rides, but otherwise had no idea. I'll be testing my levels and test levels this week or next to make sure my current 5mg daily is doing me well, but I feel good.

 

[Systemlord]

I think increased blood pressure while on TRT may be an indication of high hematocrit and/or water retention.

My blood pressure drops right after getting phlebotomized, but only for a short while. The HCT is still in range which makes me think it's fluid retention.

When I was getting phlebotomized during a period of dehydration caused by vitamin D toxicity/hypercalcemia, the phlebotomy dehydrated me even more.