While this can be helpful for some people with anemia, it can also become a problem if the levels rise too much. Once TRT has been stable for a full year, most people can move to yearly blood tests. By this point, the body has adapted more fully to the new testosterone level. Starting TRT without a baseline makes it hard to know whether future increases are from testosterone or from something else. Most high hemoglobin levels can be managed with simple adjustments if found in time. For many people, this gives a small boost in energy or stamina, but the increase can be too strong. Because of this, doctors use regular blood tests to make sure your levels stay safe. Studies show that 10–20% of people on TRT develop elevated hemoglobin or hematocrit at some point during treatment. This increase can push hemoglobin and hematocrit above the normal range. When hepcidin levels are high, your body absorbs less iron. When estradiol levels rise slightly during TRT, it can add to the stimulation of red blood cell production. Its job is to tell the bone marrow when to make more red blood cells. Each step explains why testosterone therapy often raises these blood values more than natural hormone levels do. Hemoglobin, hematocrit, and RBC count are key markers that show how your blood responds to testosterone therapy. However, many of the adaptations induced by testosterone—increased hemoglobin and hematocrit, increased red cell 2,3-bisphosphoglycerate, and increased muscle capillarity—would be expected to increase net oxygen delivery to the tissue. The increases in hemoglobin and hematocrit levels in men assigned to the testosterone arm were similar in magnitude to those reported in other testosterone replacement studies (17–20). We have reported that administration of supraphysiologic doses of testosterone in healthy men suppresses the iron regulatory peptide hepcidin while EPO levels remained unchanged after 20 weeks of treatment (12). Hemoglobin and hematocrit values often fall back into the safe range within 4 to 12 weeks, depending on the person. But if hemoglobin stays high or continues to rise despite these adjustments, stopping TRT becomes necessary. These symptoms can be a warning sign that TRT is raising hemoglobin too much. Drugs to stimulate erythropoietin, including darbopoietin, thiazide diuretics or androgen therapy (i.e., testosterone or anabolic steroids) are also common acquired causes for erythropoiesis. Congenital causes include germline mutations resulting in high oxygen affinity hemoglobinopathies, altered intracellular oxygen sensing pathways or enhanced erythropoietin receptor signalling. The Canadian Men’s Health Foundation Multidisciplinary Guidelines Task Force on Testosterone Deficiency2 and the American Endocrine Society3 recommend testosterone for men with symptomatic androgen deficiency and low levels of serum testosterone. Because his hematocrit was 58% in the setting of new onset hypertension, we also suggested urgent phlebotomy, after which his hemoglobin level and hematocrit normalized (154 g/L and 45%, respectively) (Figure 1). Results for peripheral blood testing for the JAK2 mutation, which is present in about 97% of patients with polycythemia vera,1 were negative. Historical studies in preclinical models had suggested that testosterone induces an erythropoiesis-stimulating factor, which was measured in these early studies by a bioassay using a polycythemic mouse model (5). Angelova P, Momchilova A, Petkova D, Staneva G, Pankov R, Kamenov Z. Testosterone replacement therapy improves erythrocyte membrane lipid composition in hypogonadal men. More than eight years’ hands-on experience with the novel long-acting parenteral testosterone undecanoate. Issues in testosterone replacement in older men. Jockenhovel F, Vogel E, Reinhardt W, Reinwein D. Effects of various modes of androgen substitution therapy on erythropoiesis. Complications of injectable testosterone undecanoate in routine clinical practice. Maybe your lib...Your testosterone levels look great on paper, but you feel l...Read More Your testosterone levels look great on paper, but you feel like garbage. At Revolution Health, we specialize in hormone optimization with comprehensive monitoring, ensuring you get the benefits of testosterone while avoiding complications like high hematocrit. If you’re on testosterone therapy—or considering starting—it’s essential to work with a clinic experienced in personalized hormone management. Some studies suggest that men who convert more testosterone to estrogen may experience different hematocrit responses than those who do not. While estrogen plays a protective role in cardiovascular health, it also influences bone marrow activity and iron metabolism. While the absolute risk is debated—since not all studies show high event rates—clinicians universally agree that monitoring hematocrit is essential. A potential mechanism for testosterone-induced increase in EPO levels could be via induction of hypoxia or hypoxic sensing, which could increase EPO secretion (32). These observations from mice, when taken together with data from this trial, suggest that testosterone increases iron utilization for erythropoiesis. We have reported recently that testosterone regulates hepcidin transcription in mice through regulation of bone morphogenetic protein (BMP) signaling mechanisms (26). Our findings indicate that testosterone administration recalibrates the set point for EPO in relation to the prevalent hemoglobin concentrations resulting in higher EPO levels.
