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Genetics and individual responseEvery person’s body reacts to testosterone differently. TRT adds to this effect and increases the chance of elevated hemoglobin. When breathing stops during sleep, the body gets lower oxygen levels. Older adults may also have other health conditions that increase the effect. Testosterone pelletsPellets are implanted under the skin and release testosterone slowly over several months. Some people switch to gels if they develop high hemoglobin while using injections. They may still raise hemoglobin, but the risk is a bit lower.
Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. Cardiovascular events and intensity of treatment in polycythemia vera. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men.
If someone with sleep apnea starts TRT, the combined effect can push hemoglobin even higher. Sleep apneaSleep apnea is one of the strongest risk factors. AgeOlder adults have a higher chance of developing high hemoglobin on TRT. Their risk level appears to fall between gels and injections. While the release is steady, pellets still raise hemoglobin in some users. Because of this, gels and patches have a lower chance of causing high hemoglobin compared to injections.
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).
To ensure adequate oxygenation, a sufficient hemoglobin level must be maintained. However, as we have described in several study reports published here, the widespread fear of prostate cancer and heart disease is unfounded and not supported by medical research. The section Cases presents brief case reports that convey clear, practical lessons. For example, 42% of men in the younger group who were taking a 125 mg dose achieved peak hematocrit percentages after 12 weeks compared with 75% in the older group. Thrombosis is also an important consequence of erythrocytosis. Alternatively, erythropoietin secretion can be pathologic in erythropoietin-producing malignant diseases such as renal cell carcinoma, hepatocellular carcinoma and pheochromocytoma.4
These observations do not preclude the possibility of a direct oxygen-independent effect of testosterone on the expression of hypoxia-inducible factors or on upstream regulators (VHL, PHD) or downstream regulators (HIFs primarily) of EPO transcription and secretion. Serum sTR concentration reflects total erythroid activity and iron status and has been shown to reflect plasma iron turnover and erythroid transferrin uptake if iron deficiency is not present (22,25). The limitations of this study include relatively infrequent analyses (monthly) and lack of analyses of changes in and response to hypoxia inducible factor (HIF), Von Hippel Lindau (VHL), and prolyl hydroxylase (PHD) levels/ activity that would allow for a more mechanistic interpretation. The strengths of this study include its prospective, randomized, placebo- controlled trial design, the relatively large patient population, and a sufficient study duration to assess the chronic effects of testosterone on numerous hematologic parameters. The hematologic changes in response to testosterone administration in anemic men were generally similar to those observed in nonanemic men and in the entire cohort. Evidence for occult iron deficiency was lacking in this population, as indicated by normal ferritin, serum iron and transferrin saturation, and normal mean corpuscular volume.
The effect was related to the dose of testosterone, and was more likely to occur with the higher doses, above 125 milligrams a week. The men underwent blood tests 5 times over the course of the 20-week study. This was done to more precisely determine the effects of the testosterone injections. These men were provided weekly injections of testosterone enanthate (a long-acting ester of testosterone) in varying doses of 25, 50, 125,300, and 600 milligrams over a course of 20 weeks.
Hematocrit rises when the number of red blood cells increases or when the plasma volume decreases (such as with dehydration). These checks usually include a complete blood count, or CBC, which measures hemoglobin, hematocrit, and red blood cell count. Testosterone can increase a hormone called erythropoietin, or EPO, which signals the bone marrow to make more red blood cells. Many people starting TRT do not know that testosterone is tied closely to red blood cell production. Testosterone has a strong effect on how many red blood cells your body makes. When larger doses of injectable testosterone block hepcidin, more iron is released and absorbed into the body. The study concluded that the rise in hematocrit or blood thickness, is related to the supression of hepcidin caused by high dose injectable testosterone.
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.
