Background
It is known that testosterone stimulates erythropoiesis. The mechanism behind this is still unknown. The aim of this study is to investigate testosterones effect on erythropoiesis and iron status.
Methods
In this prospective study 16 transgender males starting testosterone therapy (TT) were included. Blood was drawn at 0, 6, 12 and 52 weeks after initiation of TT. The following parameters were measured: hematocrit, testosterone, estradiol, ferritin, transferrin, iron, EPO, hepcidin and soluble transferrin receptor (sTfR). In 8 transgender males MRI scans of the liver were executed at these time points to calculate iron storage using T2* measurements.
Results
In the first year of TT hematocrit levels increased from 0.40(0.39-0.42) to 0.45(0.43-0.46). Iron storage parameters showed a decrease in the first 12 weeks but (almost) restored to baseline levels after 1 year with ferritin 37.20(30.9-43.5) at baseline and 19.8(13.7-25.9), 21.1(14.4-27.8) and 30.1(22.1-38.1) at 6, 12 weeks and after 1 year. Liver iron showed a similar trend. Iron trafficking parameters showed an increase in the first year with transferrin 2.9(2.8-3.1) at baseline and 3.2(3.1-3.4) after 12 weeks. sTfR showed a similar trend. Hepcidin showed a decrease in the first 12 weeks (baseline 7.2(4.7-9.7) 12 weeks 2.7(0-5.5)) and stayed lower after 1 year (5.0(2.5-7.6)), resulting in more iron availability. EPO showed a small increase after 6 weeks, a decrease after 12 weeks and went back to baseline levels at 1 year.
Conclusion
TT induced an increase in hematocrit accompanied by an increase in iron trafficking and decrease in stored iron in the first 12 weeks which was restored after 1 year. EPO levels didn’t show a clear increase, hepcidin decreased resulting in more iron availability for erythropoiesis. In conclusion testosterones effect on erythropoiesis cannot entirely been explained by its effect on EPO, indicating that TT might have a direct effect on the bone marrow. Body iron storages are used for erythropoiesis, in response to this mechanisms to complement these storages are activated.