Über

Blood samples from this same dose–response study were later used for measurement of the master iron regulator protein hepcidin (34). Specialized kidney cells sense pO2 and its decrease forms a strong signal to increase EPO production (25). Incidence rates might be higher in clinical practice, as both trials excluded participants with baseline hematocrit exceeding 50%, thereby decreasing the likelihood of them developing erythrocytosis exceeding hematocrit thresholds. Important differences between these two landmark trials are the testosterone formulations used (testosterone gel vs i.m. testosterone undecanoate) and higher testosterone levels reached in the T4DM trial compared with the TRAVERSE trial. Importantly, differences in dosing, i.e., target testosterone levels, might obfuscate differences between formulations.
With an increasing awareness of men’s health issues, including androgen deficiency, the use of testosterone therapy (TTh) is on the rise. This review examines the literature regarding testosterone-induced erythrocytosis and polycythemia. A patient with treatment-resistant depression and a ferritin of 9.6 µg/L needs their gut assessed and their iron stores rebuilt — not a medication adjustment. These are the are some of the biological flags that explain why patients with depression, anxiety, ADHD, CPTSD, PTSD, CKD, and diabetes plateau in treatment.Upstreaming from the treatment room to prevention, wow. Classic Simpson's paradox – men have higher hemoglobin AND higher testosterone AND higher creatinine. However, evidence supporting the efficacy or safety of therapeutic phlebotomy in lowering hematocrit in TTh-induced erythrocytosis is lacking. Besides dose adjustments, therapeutic phlebotomy or venesection is mentioned as a means of reducing hematocrit in these patients.
Or, in other words, a new ‘set point’ is established at which the same EPO level is maintained, rather than suppressed, at a higher hematocrit. A potent dose-dependent suppression of serum hepcidin was found, and this suppression was stronger in older than younger men. However, stimulation of EPO production as a mechanism was called into question by a secondary analysis of a testosterone dose–response study published in 2008 (17).
At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point. TRT often increases hemoglobin because testosterone stimulates red blood cell production (erythropoiesis). Testosterone replacement therapy (TRT) can raise hemoglobin and hematocrit because it stimulates the body to make more red blood cells. When you start testosterone replacement therapy (TRT), your body responds by making more hemoglobin, hematocrit, and red blood cells. When red blood cells increase, hemoglobin and hematocrit rise as well. The question that remains is whether decreased tissue pO2 in response to therapeutic phlebotomy in TTh-induced erythrocytosis increases HIF activity sufficiently to also confer a thrombotic risk that might offset or override the potential benefit of correcting increased hematocrit. How does testosterone replacement therapy (TRT) cause an increase in red blood cell volume?
This situation is called erythrocytosis, which is common in people using TRT. Doctors often use hematocrit as the main marker for deciding whether to adjust your TRT dose or recommend treatment such as therapeutic phlebotomy. When hematocrit gets too high, the blood becomes thicker and flows more slowly. When levels are too high, your blood can become thicker, which may lead to circulation problems. When levels are too low, you may feel tired, weak, or short of breath because your blood cannot carry enough oxygen.
Hematocrit is the percentage or proportion of blood volume that is comprised of red blood cells. Hemoglobin is a protein within red blood cells that carries oxygen. TRT induces an elevation in red blood cell count (RBC). The treatment can be testosterone replacement therapy (TRT).

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