madman
Super Moderator
The mechanism by which TRT-induced erythrocytosis occurs is due to the respective roles of hepcidin, iron sequestration and turnover, erythropoietin formation, bone marrow stimulation, and genetic factors.6
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A recent meta-analysis showed that all types of testosterone formulations lead to significant increase in hematocrit levels, with intramuscular testosterone enanthate/cypionate leading to significantly higher levels as compared to testosterone patches.7 However, this meta-analysis did not include nasal formulations and did not include comparable numbers of studies for each formulation. The goal of this review is to summarize the newest results in this field, especially regarding the nasal and oral formulations, and give healthcare professionals and patients optimal therapy guidelines.
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Endogenous testosterone levels and hematocrit
Exogenous testosterone levels and hematocrit and hemoglobin
Exogenous testosterone levels, hematocrit and blood pressure
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Differences among testosterone preparations
1) Injectable testosterone preparations
a) Enanthate/cypionate
b) Undecanoate
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2) Oral testosterone preparations
3) Testosterone gel preparations
4) Nasal testosterone preparations
5) Subcutaneous testosterone pellet
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We can see that there are major differences among testosterone preparations with regard to hematocrit increases. In general, short acting preparations that are frequently administered and lead to small increases in serum testosterone, seem to have the least side effects, whereas infrequent administration of high dose long-acting preparations seem to have more marked increases in hematocrit. Patel et al., (unpublished data, 2020), even recorded differences in the administration frequency for testosterone cypionate. Dosage levels of 200 mg every 2 weeks lead to hematocrit >54% in 8% of the patients, whereas 100 mg every week led to hematocrit >54% in 1% ofthe patients.
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Risk factors for TRT-induced hematocrit increases
Pre-TRT hemoglobin and hematocrit levels contribute to hematocrit elevations, therefore it is very important to monitor these values during TRT in patients with high preTRT hemoglobin and hematocrit levels.
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Timeline for TRT-induced hematocrit increases
One study showed that the largest increase in hematocrit happens in the first year after start of TRT, followed by ups and downs, but trending to slowly increase up to 20 years.29
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Other methods to treat low testosterone while keeping hematocrit levels within range
1) Clomiphene citrate
2) Human chorionic gonadotropin
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Treatment for elevated hematocrit levels
* Phlebotomy
* Medication
* Change of testosterone type
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Potential benefits of TRT induced elevated hematocrit levels
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Conclusion
TRT can lead to drastic increases in HCT, potentially leading to cardiovascular diseases. In an update published in 2018 to the “Testosterone Therapy in Men With Androgen Deficiency Syndromes” guideline (2010), the authors recommend against starting TRT in patients with elevated hematocrit levels.53
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Injectable testosterone formulations such as cypionate and enanthate are especially susceptible for supraphysiological increases in serum testosterone, potentially leading to elevated HCT levels. Short acting formulations such as nasal spray, topical gel, and oral formulations appear to result in lower increases in serum testosterone, usually within physiological ranges, often leading to weaker elevations in HCT. Indirect methods to increase testosterone such as HCG or clomiphene seem to have very few side effects on HCT. The cut-off number of HCT for discontinuation of TRT, ranges from 52%–54%. However, recent data suggests mortality risk reduction in the higher end of HCT (50%–52%) as compared to lower HCT(46%–49%). Therefore a 54% threshold for TRT discontinuation might be appropriate.
--------------
A recent meta-analysis showed that all types of testosterone formulations lead to significant increase in hematocrit levels, with intramuscular testosterone enanthate/cypionate leading to significantly higher levels as compared to testosterone patches.7 However, this meta-analysis did not include nasal formulations and did not include comparable numbers of studies for each formulation. The goal of this review is to summarize the newest results in this field, especially regarding the nasal and oral formulations, and give healthcare professionals and patients optimal therapy guidelines.
--------------4
Endogenous testosterone levels and hematocrit
Exogenous testosterone levels and hematocrit and hemoglobin
Exogenous testosterone levels, hematocrit and blood pressure
-----------------
Differences among testosterone preparations
1) Injectable testosterone preparations
a) Enanthate/cypionate
b) Undecanoate
-------------
2) Oral testosterone preparations
3) Testosterone gel preparations
4) Nasal testosterone preparations
5) Subcutaneous testosterone pellet
-------
We can see that there are major differences among testosterone preparations with regard to hematocrit increases. In general, short acting preparations that are frequently administered and lead to small increases in serum testosterone, seem to have the least side effects, whereas infrequent administration of high dose long-acting preparations seem to have more marked increases in hematocrit. Patel et al., (unpublished data, 2020), even recorded differences in the administration frequency for testosterone cypionate. Dosage levels of 200 mg every 2 weeks lead to hematocrit >54% in 8% of the patients, whereas 100 mg every week led to hematocrit >54% in 1% ofthe patients.
----4
Risk factors for TRT-induced hematocrit increases
Pre-TRT hemoglobin and hematocrit levels contribute to hematocrit elevations, therefore it is very important to monitor these values during TRT in patients with high preTRT hemoglobin and hematocrit levels.
--------------4
Timeline for TRT-induced hematocrit increases
One study showed that the largest increase in hematocrit happens in the first year after start of TRT, followed by ups and downs, but trending to slowly increase up to 20 years.29
----------4
Other methods to treat low testosterone while keeping hematocrit levels within range
1) Clomiphene citrate
2) Human chorionic gonadotropin
------------4
Treatment for elevated hematocrit levels
* Phlebotomy
* Medication
* Change of testosterone type
------------
Potential benefits of TRT induced elevated hematocrit levels
---------4
Conclusion
TRT can lead to drastic increases in HCT, potentially leading to cardiovascular diseases. In an update published in 2018 to the “Testosterone Therapy in Men With Androgen Deficiency Syndromes” guideline (2010), the authors recommend against starting TRT in patients with elevated hematocrit levels.53
-------------
Injectable testosterone formulations such as cypionate and enanthate are especially susceptible for supraphysiological increases in serum testosterone, potentially leading to elevated HCT levels. Short acting formulations such as nasal spray, topical gel, and oral formulations appear to result in lower increases in serum testosterone, usually within physiological ranges, often leading to weaker elevations in HCT. Indirect methods to increase testosterone such as HCG or clomiphene seem to have very few side effects on HCT. The cut-off number of HCT for discontinuation of TRT, ranges from 52%–54%. However, recent data suggests mortality risk reduction in the higher end of HCT (50%–52%) as compared to lower HCT(46%–49%). Therefore a 54% threshold for TRT discontinuation might be appropriate.
