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When hepcidin levels are high, your body absorbs less iron. This means the increase in hemoglobin is not only due to testosterone alone. Its job is to tell the bone marrow when to make more red blood cells. Testosterone has a powerful effect on the body, and one of its most important actions is increasing the production of red blood cells. Because of this, hemoglobin and hematocrit are two of the first things doctors monitor when you start TRT. Thicker blood does not flow as easily, which can strain the heart and increase the risk of complications.
Further studies are needed to test the hypothesis that testosterone stimulates erythropoiesis by increasing EPO secretion and resetting its relationship to hemoglobin and by increasing iron utilization for erythropoiesis. In addition, patients with posttransplant erythrocytosis, renal dysfunction, and some populations who live at high elevation show evidence of a new EPO/hemoglobin set point (34,43,44). It is not known whether erythrocytosis in response to testosterone administration in elderly men with mobility limitation poses risks or provides benefit. Recent studies have demonstrated that estradiol, which is the product of aromatase-catalyzed testosterone metabolism, regulates hepcidin transcription and systemic levels of hepcidin in vitro and in vivo, respectively (35–37). Our studies in mice suggest that testosterone directly suppresses hepcidin transcription independently of its effects on EPO levels (26). 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). We have reported recently that testosterone regulates hepcidin transcription in mice through regulation of bone morphogenetic protein (BMP) signaling mechanisms (26).
The iron panel, thyroid, and B-12 labs were found to be within normal limits, so the unexplained asymptomatic anemia was postulated to occur from testosterone deficiency as the patient was found to have hypogonadism on physical exam. A longitudinal study in Italy provides further evidence by demonstrating that older men and women with testosterone levels in the lowest quartile were more likely to develop anemia than those subjects in the other three quartiles over a follow-up period of three years . Boys with delayed puberty have been demonstrated to have hemoglobin levels similar to girls and prepubertal boys . This is evident in studies showing high rates of hypogonadism in patients on antipsychotic treatment . Prolactin inhibits gonadotropin-releasing hormone (GnRH), leading to reduced testosterone levels. Both patients in this case were approximately 20 years post-andropause, and it is not surprising that there was testosterone deficiency.
What is the risk of elevated hematocrit levels and increased red blood cell volume induced by testosterone therapy? By being informed about the potential for increased hemoglobin and hematocrit with testosterone therapy, patients can work with their healthcare providers to manage this risk effectively and maximize the benefits of treatment. Testosterone replacement therapy (TRT) can raise hemoglobin and hematocrit levels because it increases the body’s production of red blood cells.
Transdermal gels and patchesGels and patches deliver testosterone in a steady way across the skin. Intramuscular injectionsInjections, especially long-acting ones, are the form most likely to raise hemoglobin. Some research even finds rates as high as 30%, depending on the testosterone dose and how it is given. This does not mean TRT always causes dangerously high hemoglobin. TRT often raises testosterone much higher, especially right after injections. Hepcidin is a liver hormone that controls how much iron your body absorbs.
Lowering the dose can often bring hemoglobin back down without stopping treatment. While this can be helpful for some people with anemia, it can also become a problem if the levels rise too much. Even if your levels have been stable in the past, changes in lifestyle, health, or dosage can affect hemoglobin levels later. Once TRT has been stable for a full year, most people can move to yearly blood tests. 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.. Here, we review the literature examining testosterone-induced erythrocytosis and summarize proposed mechanisms and risks of thromboembolic sequelae. However, little evidence supports an increased risk of these negative sequelae in men on TTh . The authors acknowledged the lower prevalence of hypogonadism in consideration of both serum testosterone levels and symptoms, noting that "this finding underscores the paramount importance of using not only biochemical measures but also stringently defined, symptom-based criteria to prevent over diagnosis…". Further assessment of the cohort with an evaluation of nine candidate symptoms in addition to low testosterone levels found a prevalence of 2.1% for symptomatic hypogonadism (low T with at least 3 symptoms) . Hypogonadism is defined as "biochemically low testosterone levels in the setting of a cluster of clinical symptoms, which may include reduced sexual desire (libido) and activity, decreased spontaneous erections, decreased energy and depressed mood" .|Bachman et al. theorized that testosterone causes suppression of hepcidin leading to an increase in iron absorption for erythrocytosis to occur. While this regimen of testosterone is supra-physiologic in order to induce erythropoiesis, more standard dosing regimens by men today of 100mg testosterone injection weekly typically increases hemoglobin levels by only 10g/l. It is specifically the red blood cell component of total blood volume that is increased by TRT. Erythrocytosis is an increase in red blood cell count that may impart a risk to the cardiovascular system.|If levels become too high, lowering the dose or donating blood can help. Managing High LevelsIf hemoglobin or hematocrit exceeds safe limits Monitoring is crucial for both men and women on testosterone therapy. This new equilibrium set point for EPO/hemoglobin has precedent in the observation that men and women have different hemoglobin reference ranges yet similar EPO levels (42). The clinical consequences of testosterone-induced erythrocytosis in men remain to be elucidated.|If hemoglobin or hematocrit becomes too high, therapeutic phlebotomy may be recommended. This is why it’s important to look at the whole picture, not just testosterone levels. Some people respond better to methods that provide steady hormone levels rather than sharp peaks.|Testosterone stimulates the body to make more red blood cells. For people on TRT, many clinicians consider a hematocrit of 54% or higher a level where treatment changes should be discussed. While RBC count alone does not show how thick the blood is, it helps doctors understand why hemoglobin or hematocrit may be changing. This number helps support the hemoglobin and hematocrit results. The RBC count measures how many red blood cells are present in a certain amount of blood. This can increase pressure inside blood vessels and may raise the risk of blood clots if left untreated. Hematocrit is the percentage of your blood that is made up of red blood cells.|These symptoms can appear even with mild rises in hemoglobin and hematocrit, so they should not be ignored. These symptoms happen because the blood becomes thicker, moves more slowly, and increases the workload on the heart and blood vessels. Knowing the factors that raise the risk of high hemoglobin helps both patients and healthcare providers plan safer treatment. SmokingSmoking lowers oxygen levels in the blood and forces the body to make more red blood cells. Because of this, injections are linked with the highest rates of erythrocytosis (high red blood cell concentration).|This explains why two people on the same dose may have very different lab results. Genetics and individual responseEvery person’s body reacts to testosterone differently. TRT can amplify this effect, making high hemoglobin more likely. Many providers screen for sleep apnea before starting therapy. If someone with sleep apnea starts TRT, the combined effect can push hemoglobin even higher. When breathing stops during sleep, the body gets lower oxygen levels.}
When oxygen levels fall, the body reacts by producing more red blood cells to try to carry more oxygen. Smoking thickens the blood, damages vessels, and increases clot risk. When TRT increases these levels, blood becomes thicker. High hemoglobin and high hematocrit are two of the most common side effects of testosterone replacement therapy (TRT). Because of this, people using injections often need more frequent blood tests to monitor their red blood cell count.
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