Thus, increased hemoglobin and hematocrit would normally be expected to suppress serum EPO levels. The vertical shift in the top two panels indicates increased EPO per hemoglobin or hematocrit at end of testosterone treatment. Serum EPO levels trended toward baseline by 6 months in spite of continued testosterone administration, but remained nonsuppressed in spite of elevated levels of hemoglobin and hematocrit in testosterone-treated men. However, it’s essential for patients to be aware of potential side effects, including an increase in hemoglobin and hematocrit (red blood cell count), which can lead to a condition called polycythemia or erythrocytosis. Testosterone therapy can increase red blood cell production, measured by hemoglobin (Hb) andhematocrit (Hct) levels. 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). Testosterone can raise hemoglobin and hematocrit because it increases the production of red blood cells. Kennedy and Gilbertsen in 1957 demonstrated in an observation study of women with breast cancer treated with androgen therapy (100mg testosterone injections three times weekly), significant increases in red blood cell volume. This study was followed by further work by Bachman that hypothesized a multifactorial model suggesting that "testosterone stimulates EPO transiently, along with suppression of hepcidin, and these two mechanisms result in a new EPO "set point" at a higher physiologic level of hemoglobin" . Initial hypotheses posited increased production of erythropoietin (EPO) by the kidneys, and subsequent studies suggested direct stimulation of erythroid progenitor cells; however, more recent studies in humans have not supported this mechanism 11, 23, 51–55. Conversely, numerous studies have conflicting results, observing no increased risk of thromboembolism with persistent Hct elevations. Polycythemia and erythrocytosis are used interchangeably to refer to an abnormal elevation of hemoglobin (Hb) or hematocrit (Hct). While practice guidelines on testosterone therapy for hypogonadism exist, there are no large-scale, randomized clinical trials assessing the use of testosterone replacement therapy in men with hypogonadism to evaluate its effect on anemia. Decreased testosterone levels are often under-recognized as a cause of anemia in males with hypogonadism. Future trials should evaluate how TTh affects the HIF-EPO pathway and how its resulting erythrocytosis might impact thrombotic risk. This makes the blood thicker and less able to flow smoothly through small blood vessels. This condition is called erythrocytosis, and it is one of the most common side effects of TRT. Thick blood moves more slowly and puts extra strain on the heart and blood vessels.
