T Nation

Study: Injection Frequency, Not Dosage, Indicates Risk of Polycythemia


Positive univariate associations between polycythemia (hematocrit >0.50) and log(testosterone) (odds ratio (OR) 24.7, 95% confidence interval (CI): 4.3, 141.2, P <0.01) and age (OR 1.1, 95% CI: 1.0, 1.1, P =0.03) and a borderline relationship with current smoking (OR 4.2, 95% CI: 0.9, 20.0, P =0.08) were unveiled. A sensitivity analysis using alternate definitions of polycythemia was performed to capture all potential covariants. Multivariate regression analysis incorporating all potential covariants disclosed the independent OR of developing polycythemia (after adjusting for smoking and age) for log(testosterone) to be 15.0 (95% CI: 2.5, 90.8). Duration of testosterone therapy did not alter the risk of polycythemia. A direct relationship between testosterone and erythropoietin was observed ( P =0.05).


Higher trough serum testosterone concentrations but not duration of treatment predict the development of polycythemia in men receiving long-acting depot testosterone treatment.

Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets


Short acting injectable testosterone is associated with greater risk of erythrocytosis when compared with other formulations. The mechanism of the pathophysiology and its role on thromboembolic events remains unclear, though few data support an increased risk of CV events resulting from testosterone-induced erythrocytosis.

Erythrocytosis Following Testosterone Therapy

sTfR levels

sTfR levels were not significantly different between young and older men at baseline. The changes in sTfR levels did not differ among the five dose groups either in young or in older men (ANOVA, young men P = 0.08, older men P = 0.054, Fig. 2B[​2B).]). The percent change in sTfR levels during treatment was not significantly different between the young and older men. There was no significant difference in percent change from baseline in serum sTfR levels across testosterone dose groups in either younger or older men (Fig. 2B[​2B]).

Testosterone dose or serum total and free testosterone levels were not significantly correlated with changes in sTfR levels (Fig. 2D[​2D]).


Despite the strong association of testosterone dose and erythrocytosis, we found no dose-dependent effect of testosterone enanthate on erythropoietin or sTfR levels. Testosterone-associated increase in hemoglobin was not accompanied by a significant increase in erythropoietin or sTfR levels. Thus, the greater increase in hematocrit and hemoglobin observed in older men during testosterone therapy is not explained by the changes in erythropoietin and sTfR levels.

Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men

Cliff notes in layman’s terms please…

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Basically this data indicates that those that carry a higher trough TT number are at more risk for polycythemia, or increased blood count, thicker blood.

So the more frequently you do injections the higher your trough will be, on average, but the lower your peaks will be.

So this data supports doing less frequent injections if you have trouble keeping your HCT in control.

Hope that makes sense.


I have experience excess RBC when RBC is closing in on 6.0 (HCT 48.4) oversupplenting iron or while on TRT. Doctors dismissed it do to being “in range”, even though the symptoms fit perfectly. I even got red pinhole marks on shins that appeared rapidly, stopping iron supplements saw a rapid decline in these marks.

I also had a burning sensation in feet and lower legs, elevated body temperatures, rapidly rising insulin levels and rapid heart rates. Red burning hands when low to the body or especially while taking hot showers, raising hands above head saw redness disappear instantly.

I recently diagnosed with long term severe iron and potassium deficiency, was iron deficient long before starting TRT almost 3 years ago.


So it has nothing to do with large peaks at all just trough? Is that what the study is sayimg and what you believe?

Yea pretty much. I wouldn’t say nothing to do with larger peaks, but seems the body is more tolerant to large peaks than it is with consistently high trough levels. If you read further into the study you can see this was proven with undecanoate dosages:


Secondary polycythemia can occur after testosterone therapy, although the risk varies depending on the actual formulation. Randomized studies in hypogonadal men show that more erythrocytosis is induced with i.m. injections of 200 mg testosterone enanthate every 2 weeks compared with 5 mg testosterone patches applied transdermally daily [(1) or with 100 mg compared with 50 mg of transdermal testosterone [(2)]. On the other hand, i.m. injections of 250 mg testosterone enanthate every 3 weeks, oral testosterone undecanoate 160 mg/day, or subcutaneous implantation of 1200 mg crystallized testosterone are equivalent [(3)]. 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

That to me, unless I am reading it wrong is only talking about how long it is in supraphysiological range. The longer it is in that range is when it becomes a problem. If I am misunderstanding please correct me and point where I am missing something. So to me as long as I am not trying to ride high and supraphysiological I should be fine should I not?

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That is pretty much the sum of it, but we know that the more frequently you inject, the higher your trough is going to be per mg, and this affects the average.

Which is my point in saying that it is more about injection frequency than it is actual dosage.

One guy can do 150 mg per week, another can do 20mg per day, and the daily dosage will lead to polycythemia more often than the same weekly dosage.

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Good to know as my doc has me on daily subq so if it does become an issue I have options of what I can do. I was led to believe it was more of the supraphysiological peaks so you could get higher trough readings between spaced out injections that was a problem.

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Well with more spaced out injections you will get lower trough readings.

If your protocol is working I wouldn’t think to much into it, this thread was started just to show how there are many different ways to do TRT and everyone is specific to their needs. So one size fits all protocols just don’t work.

But at least you know, if HCT becomes a problem, then you could try more spaced out injections and see if it helps.


My HCT and RBC is lower on daily injections versus spreading out injections, it may be the only way to do TRT for me.

Can’t say its working quite yet as I just switched from cream to injection so not sure how its going to go. Only have about 1 week of injections so will see.

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So you do the exact same dosage you did on weekly injections, broken up daily and your HCT is lower?

Hey man, don’t mean to hijack the thread. I’m suspecting that I have Iron Deficiency anemia because of my low HTC/MCV… HTC is 3 points under normal and MCV is only 1 point under. and low-normal HGB WHILE on TRT (HGB was low pre-TRT). My ferritin is 67 which is supposedly normal but for my age I read that optimal levels would be around 110-150. What dose do you think I should take? Is 28mg of Iron every day too much or should I do it every other day? I’m also hypothyroid (possibly due to being mildly anemic)
Forgot to mention I had anemia coupled with iron deficiency when I was younger (11-12 years old)

Whenever I inject less frequently (EOD) I need more T to get to similar levels versus when on a daily protocol. Basically 7mg ED 49mg weekly after only 3 weeks got me 416 ng/dL, Free T 15 pg/mL, I need 24mg EOD (96 mg weekly) to see Total T 500 ng/dL.

The later protocol is what produced the excess red symptoms, the 7mg daily protocol had HCT at 43% and RBC 5.2, note I had 3 more weekly to go on this protocol. I notice everything across the board is lower when using less T and injecting more frequently and I feel better as a result.

I gather more T used, more red cells. It was a massive difference between daily and EOD protocols.

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Well your dosage on the QOD schedule was like 75% more, so even though you were injecting less frequently, your trough was still higher. So that doesn’t really tell us much about this data.

I bet if you did 12mg per day vs 24 QOD your HCT would not be impacted as much with the QOD schedule, but the difference would be minimal. You would really have to space injections out to see a profound difference.

Just you know a 6 RBC is not very high, the range usually goes up to 5.69. So I doubt you had any symptoms attributed to polycythemia with that and 48 HCT. Sounds like a case of over thinking it :slight_smile:

Technically you do not have polycythemia unless hemoglobin, RBC and RBC volume are all out of range.

Your HCT was 48 and was perfect. I would bet your endurance is low all the way down at 43%.

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There’s other variables involved. I had a high hct, rbc and hg regardless of dosage or frequency. 100 mg once a week, 40 mg every 3.5 days, 72 mg every 5 days. None of the numbers budged until I finally donated blood.

Like what?

What else could someone do besides reduce their trough readings to lower HCT?

Supplement with naringrin. That’s basically your only option, outside of regular blood donations. I have high HCT and it’s been tough to get under control.

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What is your injection schedule?