TWICE PER WEEK TESTOSTERONE INJECTIONS ARE ASSOCIATED WITH GREATER RISK OF HIGH HEMATOCRIT

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GreenMachineX

Well-Known Member
MP76-05 TWICE PER WEEK DOSING OF INTRAMUSCULAR TESTOSTERONE (T) IS ASSOCIATED WITH GREATER RISK OF ERYTHROCYTOSIS

I wish they had tried 50 mg twice per week instead of 80-150 mg twice per week.

INTRODUCTION AND OBJECTIVES
With an increasing awareness for mens health, marketing for pharmaceutical sales of testosterone products has increased over 170% over the last 5 years as reported by Layton et. al with a 100-fold increase in the market over the last 3 decades. The most common dose-limiting adverse effect of testosterone therapy (TTh) is erythrocytosis, which may exacerbate pre-existing vascular disease and increase the risk for thromboembolic complications. The increased risk of erythrocytosis with injectable testosterone over that of topical applications has been established. We sought to determine if the incidence of erythrocytosis, as defined by a hematocrit (Hct) > 52%, in patients on injectable TTh was significantly changed by more frequent, lower dose T injections.

METHODS
A sample of 55 men using injectable T (cypionate or enanthate) for symptomatic hypogonadism at a single dose and frequency was selected for analysis from a single center mens health database. Age, T dosage, frequency of administration, duration of T therapy, and Hct were extracted through retrospective chart review. The cohorts were separated into 27 men on 200mg of T once weekly (QW) and 28 men on 80-160mg of T twice weekly (BIW). Indication for BIW dosing was a return of hypogonadal symptoms prior to the administration of the next dose. The maximum Hct was identified for each individual and the cohort mean of the maxima was calculated. The difference in numerical variables was assessed via Mann-Whitney U analysis.

RESULTS
No significant difference was identified between the mean (range) age of the QW and BIW cohorts (43.2 (27-63) years vs. 40.6 (27-62) years), respectively (p=0.36). Erythrocytosis occurred in 11% of the QW cohort with a maximum Hct (Interquartile Range) of 49.2 % (43.4, 54.6). In contrast, a maximum Hct of 51.4 % (45.7, 56.9) was observed in the BIW cohort, with 29% of men developing erythrocytosis. Statistical significance was identified in comparing the percent erythrocytosis of the two cohorts (p=0.007). The rate of erythrocytosis, defined as the number of days until maximum Hct while on testosterone, was comparable in both groups (p=0.18).

CONCLUSIONS
Although the rate of erythrocytosis is comparable among BIW and QW dosing, more frequent dosing of injectable T is associated with a higher maximum Hct and a higher incidence of erythrocytosis. These data suggest that dosing frequency, rather than total T dose, is an important factor in development of erythrocytosis in men on injectable TTh.


American Urological Association

According to this study someone on another forum posted, twice per week injections was associated with higher hematocrit than once per week injections. Anyone have any thoughts?
 
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Usually hct lvls are highly correlated to trough levels. Less frequent injections = lower trough. I always believed there is a personal testosterone threshold level were rbc productions gets in high gear. The more time above that threshold the higher hct. But just speculating. My personal experience tells me this is true.
However this study uses different total dosages and is not really helpful in proving anything. I posted one here about hct and trough lvls correlation
 
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Then there is this study:

Daily subcutaneous testosterone for management of testosterone deficiency
https://www.bioscience.org/2018/v10e/af/825/fulltext.php?bframe=2.htm

"Testosterone replacement inhibits hepcidin activity, thereby leading to increased iron absorption and increased erythropoiesis. It is plausible that smaller daily testosterone injections, resembling physiologic secretion, do not affect hepcidin activity to the same degree that is seen with supra-physiologic testosterone level from weekly IM injections."
 
This is all starting to get confusing. In regards to HCT, one study says one thing, another says the complete opposite. Anecdotally, it seems that forum members present the same results - some say they reduced HCT by injecting more frequently, others say that their HCT actually went up on more frequent injections.

We seem to see the same thing with E2 - some say more frequent injections lower E2, others say they made things worse.

Sure would be nice if there were some handrails on this walkway lol...
 
It almost seems like the people doing this clinical study just picked a dosage off the top of their head and went with it without any idea what's being employed in therapeutic TRT.

If this clinical study were more conservative I'm certain the outcome would have been more favorable to twice weekly dosing.

The problem with TRT is you have to tailor treatment to the patient and everyones needs will be unique, there is no cookie cutter approach that will work.
 
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Apparently they only measured trough testosterone. In addition, they are studying pellets, which give relatively steady levels for long periods. In other words, I don't think these results are particularly applicable to injections with much shorter cycles. The working theory is that longer periods at supraphysiological testosterone levels cause the increase in risk.
As a unifying hypothesis, these data suggest that both the dose and pharmacokinetics of specific testosterone formulations (rather than the actual route of administration) are important because both influence the relative amount of time blood testosterone concentrations remain in the supraphysiological range. Indeed, others have postulated that the increased rates of polycythemia with short-acting testosterone esters are due to supraphysiological levels of testosterone (1, 4, 5). If true, longer acting testosterone preparations such as testosterone implants and i.m. injections of testosterone undecanoate, which do not cause prolonged supraphysiological testosterone levels when administered at appropriate doses (6), may therefore result in a lesser degree of erythrocytosis. In support of this hypothesis, direct relationships between testosterone and hematocrit have already been demonstrated (2, 3, 7).
 
And then you can certainly have a well defended argument that any Erythrocytosis is benign and otherwise a misdiagnosed PCV. ASn increase in one or even two blood factors might not be anything, an increase in all blood factors, which is PCV, would be cause for concern. Then too you can even break it in to being Platelets and not HCT/HGB/RBC.
 
And then you can certainly have a well defended argument that any Erythrocytosis is benign and otherwise a misdiagnosed PCV. ASn increase in one or even two blood factors might not be anything, an increase in all blood factors, which is PCV, would be cause for concern. Then too you can even break it in to being Platelets and not HCT/HGB/RBC.
Dr. Saya has argued that the dangers are not so much the acute ones, such as strokes, but the ones related to chronic stress on the vasculature.
Dr. Justin Saya said:
BP (and the resultant stress on the vascular system) is what folks really need to watch (and be concerned with longterm) with high(er) hematocrit levels. Not the misrepresentation of blood clotting, misnomer of polycythemia vera, or countless other distractors that folks (practitioners and lay folks) debate somewhat meaninglessly. Is it pure coincidence that males have (as general comparison to females): almost invariably higher hematocrit levels...higher blood pressure measurements...higher incidence of cardiovascular events...

There’s a lot more to it, but food for thought nonetheless.
[1]
 
Dr Saya, my great Dr, hasn't moved with his some of his colleagues on this and we do disagree on it and I continue to respect and abide by his directive to donate but we do not see eye to eye on this.
 
The working theory is that longer periods at supraphysiological testosterone levels cause the increase in risk.

What serum level is considered supraphysiological levels? Anything over 916 ng/dl is considered high on current standard tests? But 916 while high doesn't seem supraphysiological.

Is there a level of total T generally agreed by those on excel male as too high?
 
I saw the report at the same time that my switch to 2x/ week protocol sure enough raised my HCT and RBC. As noted previously- it’s not a big deal- erythrocytosis (high RBC) is not the same as Polycythemia (high platelet count). The former is common with just about anyone living at high altitudes while the latter presents a cardiovascular risk. My platelet count was normal so two doctors did not even recommend giving blood. However, I gave anyway because I did not want to risk getting taken off TRT in case things went too high or I had to get TRT managed by a different doctor. I gave blood twice - 2 months apart - which knocked my HCT from 51.5% to 47% and RBC back in normal ranges. I’ll plan on donating again this year but not because I’m worried about anything - it’s a good thing to do plus keeps things in check (if god forbid I had to rely on another doctor for TRT many do not understand the difference between erythrocytosis and polycythemia and will take you off TRT if things go high even though there really is no risk)
 
interesting, this is actually a trend I saw when going from 2 x week to 3 x week, my Hemoglobin jumped from about 16.5 to 17.2, I tried daily injection and it made now difference. Sometime I really think the best protocol was the 2 x week injections.

I thought about this a few times, and wondered why people get a raise in Hemoglobin during the first 6 months year of TRT then it stabilize, and with me the reverse happened. Well after a year an half I went to 3 x week injections.
 
Beyond Testosterone Book by Nelson Vergel
interesting, this is actually a trend I saw when going from 2 x week to 3 x week, my Hemoglobin jumped from about 16.5 to 17.2, I tried daily injection and it made now difference. Sometime I really think the best protocol was the 2 x week injections.

I thought about this a few times, and wondered why people get a raise in Hemoglobin during the first 6 months year of TRT then it stabilize, and with me the reverse happened. Well after a year an half I went to 3 x week injections.


I had the same thing in terms of it happening in reverse. Mine sat around 45-47 for 5 years until just recently, I got three consecutive readings over 51. No change in dosage, no change in BW or any of that, practically the same exact workout as before, I've been drinking a gallon of water for the past month or so and taking grapefruit seed extract. I did donate for the first time last week and we'll see if the extra hydration,grapefruit and donation make a difference. What's even stranger is that when I was a kid and would go for a physical, even into college, they always remarked that my Hg and HCT were borderline low wand I should keep an eye on it.
 
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