Best possible method of Minimizing Erythrocytosis during TRT (Daily injectables vs. Gels vs. Kyzatrex)

[AndrewP]

All,

I react very badly to injectable T (56 hematocrit @ 100 mg split 3x per week SubQ). My ferritin suffers greatly here and sits in the 20's to low 30's. I want it to be above 70. Testosterone have given me a severe case of periodic limb movement disorder due to low dopamine resulting (I think) from my Ferritin dropping from 130 to 30. Here are my questions:

Studies suggest testosterone pills (Kyzatrex, Jatenzo) pose the most limited effect on hematocrit.. Followed by patches (not available) followed by cream, with Injections being the worst contributer.. But.. why?

Infrequent injection intervals used in studies? Or, estrogen spikes from injectables? Something else?

I would like to do daily cypionate injections. However, if that can't match the profile of testosterone pills than I have to take that option.

Is there any reason why T pills would be better than daily low dose SubQ Cypionate injections for erithrocytosis? Has anyone ever had personal experience with this?

Your advice is extremely appreciated!!

 

[madman]

All,

I react very badly to injectable T (56 hematocrit @ 100 mg split 3x per week SubQ). My ferritin suffers greatly here and sits in the 20's to low 30's. I want it to be above 70. Testosterone have given me a severe case of periodic limb movement disorder due to low dopamine resulting (I think) from my Ferritin dropping from 130 to 30. Here are my questions:

Studies suggest testosterone pills (Kyzatrex, Jatenzo) pose the most limited effect on hematocrit.. Followed by patches (not available) followed by cream, with Injections being the worst contributer.. But.. why?

Infrequent injection intervals used in studies? Or, estrogen spikes from injectables? Something else?

I would like to do daily cypionate injections. However, if that can't match the profile of testosterone pills than I have to take that option.

Is there any reason why T pills would be better than daily low dose SubQ Cypionate injections for erithrocytosis? Has anyone ever had personal experience with this?

Your advice is extremely appreciated!!

I react very badly to injectable T (56 hematocrit @ 100 mg split 3x per week SubQ).

I hope you understand that one can still easily hit a high-end/high trough FT injecting 100 mg T/week especially when split into more frequent injections.

Your trough FT is most likely high and even then where did your hematocrit sit before starting TRT?

Have you ever been tested for sleep apnea?

What was your trough TT and more importantly trough FT level on such protocol?




Studies suggest testosterone pills (Kyzatrex, Jatenzo) pose the most limited effect on hematocrit.. Followed by patches (not available) followed by cream, with Injections being the worst contributer.. But.. why?

Infrequent injection intervals used in studies? Or, estrogen spikes from injectables? Something else?

Comes down to the testosterone formulation, dose of T let alone pharmacokinetics (PKs) as in the majority of cases when using injectable T it is not only due to the big swings in peak--->trough but also how high a FT level you are running at trough/steady-state.

Most struggling with elevated hematocrit are running around with inflated T levels 24/7 well beyond their natty genetic set-point and this is not just at the peak we are talking about here it is also trough/steady-state!

Even when moving to more frequent injections which will result in clipping the peak--->trough many are still running too high a steady-state FT level which will still have a significant impact on driving up hematocrit.

One can still easily drive up hematocrit when using transdermal T (gel/cream) if you push your FT level too high.

Lookup some of the absurd doses being used with the compounded transdermal T creams!

With oral TU one can still achieve a high peak but it's short-lived and temporary due to the PKs.

It is dosed 2X daily (2 peaks/troughs).

Again the two daily peaks are short-lived let alone Cavg T levels are well within the physiological range.




I would like to do daily cypionate injections. However, if that can't match the profile of testosterone pills than I have to take that option.

2 different animals here when it comes to the PKs!

Daily injections using esterified TC or TE let alone TP could never mimic such.

Hematocrit on gel vs injections

After having issues with injection absorption, I recently switched to testogel and the results have been surprisingly good. Using the technique of showering, exfoliating and applying lotion, it feels like my levels have skyrocketed and stay elevated well into the next day. I am pretty sure that...

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My reply:

T formulation, the dose of T, PKs, genetics (polymorphism of the AR), age all play a role in the impact a trt protocol will have on blood markers (RBCs,hemoglobin and hematocrit).

Other factors such as sleep apnea, smoking, asthma, COPD can have a negative impact on hematocrit.

Injectable T has been shown to have a greater impact on increasing HCT compared to transdermal T.

3–18% with transdermal administration and up to 44% with injection.

In most cases when using injectable T high supra-physiological peaks post-injection and overall T levels (running too high TT/FT level) will have a big impact on increasing HCT.

Manipulating injection frequency by injecting more frequently using lower doses of T resulting in minimizing the peak--->trough and maintaining more stable levels may lessen the impact on HCT but it is not a given.

As again running very high TT/FT levels steady-state will have a stronger impact on driving up HCT.

Although injectables have been shown to have a greater impact on HCT you can see even when using a transdermal formulation that maintains stable serum concentrations that the impact it has on HCT is DEPENDANT ON THE DOSE AND SERUM LEVEL OF T.

Using higher doses of transdermal T and achieving higher TT/FT levels will have a great impact on HCT levels.

How high an FT level you are running is critical.

It is a given that most men on trt struggling with elevated RBCs, hemoglobin and hematocrit are running too high an FT level.

Sure some men are more sensitive than others as they may still struggle with elevated blood markers when running lower T levels but it is far from common and many may already have an underlying health issue contributing to such.

If you are struggling with such blood markers then in most cases finding the lowest FT level you can run while still maintaining the beneficial effects may very well be the solution.

Easier said than done as many men on trt tend to do better running higher-end FT levels within reason.

Mind you some are lucky and never have an issue or levels tend to stabilize over time.

Others will continue to struggle until the cows come home.

Testosterone Therapy and Erythrocytosis - the most common dose-limiting effect of testosterone therapy

https://www.thebloodproject.com/cases-archive/testosterone-therapy-and-erythrocytosis-2/ Introduction Androgens play a crucial role in the development and maintenance of: Male reproductive and sexual functions Body composition Erythropoiesis Muscle and bone health Cognitive function...

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Risk factors for developing erythrocytosis after testosterone therapy include:

• Obstructive sleep apnea
• Advanced age
• Obesity
• Type II diabetes mellitus
• Elevated baseline hematocrit (>50%)
• Those who live in high altitudes
• Testosterone formulation, dose and pharmacokinetics
  
  • Short-acting intramuscular (IM) formulations result in supraphysiological testosterone levels achieved days after administration.
  • Extended-release injectable testosterone and transdermal options maintain physiological testosterone levels more effectively and reduce the risk of secondary erythrocytosis.

• Risk/rate of erythrocytosis according to formulation:
  
  
  • Intramuscular injections – 40%
  • Subcutaneous pellets – 35%
  • Transdermal – 15%
  • Androgel – 3%
  • Intranasal testosterone – 0–2%
  • Oral testosterone – 0.03%

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post #13

Oral testosterone. Who's on it?

Who here is on some form of oral. jatenzo/Kyzatrex? What has it done for you? What are your numbers? Has RBC increases been as much as a problem for you on the orals? How is your liver tests? Thank you

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post #7

Effects of testosterone treatment on human erythrocyte lifespan

https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgae434/7697829?redirectedFrom=fulltext&login=false Conclusions We conclude that hypogonadal men have reduced erythrocyte lifespan and acute androgen-induced increase in circulating erythrocyte lifespan may contribute...

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*Similarly, circulating erythrocyte and hemoglobin concentrations are increased by exogenous androgen treatment (5-7) including therapeutic doses (7-13) or illicit androgen abuse (14); however, the mechanism is not fully understood. The mechanism is believed to involve androgen stimulation of renal erythropoietin (Epo) leading to increased synthesis of early-stage erythrocytes (reticulocytes) and thereby increased blood hemoglobin; however, other molecular mechanisms involved, including those regulating the body’s iron economy (15), are not fully understood.

*One mechanism is that testosterone stimulates renal Epo secretion which then stimulates bone marrow erythroid production via the increased circulating Epo

*Over time, however, circulating Epo concentrations establish a new equilibrium with circulating testosterone (1). Aromatization of testosterone to estradiol to activate estrogen receptors is not required (8, 9, 25), and may partially antagonize (24), the erythropoietic effects of testosterone.

*Iron deficiency could limit the blood hemoglobin response to testosterone through a shortened erythrocyte lifespan but also by limiting erythrocyte and hemoglobin synthesis via effects on hepcidin (16, 28). Testosterone administration reduces circulating hepcidin (19) thereby increasing gut iron absorption and enhancing hemoglobin synthesis, a mechanism inhibited by iron deficiency (50, 51).

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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[Cataceous]

...
I would like to do daily cypionate injections. However, if that can't match the profile of testosterone pills [then] I have to take that option.
...

As @madman suggests, cypionate alone is less likely to be a good solution; you'll end up with fairly constant serum testosterone. There is some support for the idea that side effects can be reduced without loss of benefits if peak testosterone is preserved in the healthy normal range while average and trough testosterone are lowered. If you can obtain both cypionate and propionate then injecting a blend is a good option for achieving this. The resulting diurnal rhythm in serum testosterone doesn't perfectly mimic a natural rhythm, yet I believe it is good enough—better than all but patches—and offers advantages over the other methods, usually in cost and precision of dosing.

Tips on how to blend propionate with enanthate (or cypionate)?

I have been having some success with low dose daily propionate for the last several months. Dose levels have ranged from 8-10 mg injected every morning after waking. Overall, it has been a far better experience than my previous cypionate protocol of 80-100 per week (split every 3.5 days)...

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[Cataceous]

...
So for now, unique circumstances, I have been able to get Rx for Kyzatrex, but won't be starting it for a few more weeks. ...

Have you ruled out sleep apnea as a possible contributing factor?

Another option to try is testosterone nasal gel, if you can get it. It's the shortest acting testosterone we have. Basically you're relying on natural production to fill in the gaps between the 2-3 daily exogenous pulses.