This is an excellent question, which requires a pretty complex answer. But the basics lie in the differences between chronic hypoxia induced erythrocytosis and exogenous testosterone induced erythrocytosis.

First, the similarities:

1. Both cause elevated red blood cell counts without an increase in blood volume. This makes the blood thicker (increased viscosity). This means that the blood is more sludge like and has trouble making its way through the smallest blood vessels (capillaries).

2. Both are caused by increased erythropoietin secretion, which stimulates the blood marrow to produce more red blood cells.

Now, the differences:

1. Hypoxia only effects erythropoietin levels to raise hematocrit. Testosterone raises hematocrit through multiple mechanisms.

2. Chronic hypoxia (high altitudes, COPD) takes a long time to develop, often several years. This gives the body some time to adjust. Testosterone induced erythrocytosis can occur in as little as 3 months. This is not enough time for the body to develop any adaptive measures.

3. Chronic hypoxia also causes other changes, which testosterone use does not. Specifically, the body creates more significantly more capillaries. These capillaries create more pathways for the thicker blood to go through, distributing the vessel wall burden, and also creating alternative pathways if a clot were to occur.

4. Exogenous testosterone also causes downstream effects which hypoxia does not, such as thromboxane A2 receptor density and aggregation responses. The latest studies show that increased risk of arterial clotting is low with testosterone. However, the combination of increased blood viscosity along with increased platelet activity and thrombopoiesis triggered by testosterone can raise the risk of potential clots in those who ALSO have pre-existing coagulation or fibrinolysis dysfunction.

It is important to remember that testosterone is used at a treatment for idiopathic/immune thrombocytopenic purpura (ITP) which is a problem with too few platelets causing potentially fatal bleeding.

So, the main reason why we recommend therapeutic phlebotomy/routine blood donation for men on TRT with elevated blood counts, is because unlike people at high elevations, TRT also comes with elevation in platelet counts and platelet activity. Also, remember that the TRT patient at sea level does not need the extra RBCs, but the patient at the high elevation does. Telling them to donate blood while remaining in a state of hypoxia effectively makes them anemic.