In other families, the precise mechanism underlying the development of polycythemia remains unidentified. In one large Finnish family with polycythemia, a point mutation was identified in the erythropoietin receptor that resulted in truncation of the 70 amino acids in the carboxyl terminus, including the site where SH-PTP1 binds to turn off signal transduction. Measurement of serum erythropoietin levels has suggested that in some families, there is a primary abnormality in the set point of the renal oxygen-sensing mechanism. In these families, no abnormality in hemoglobin-oxygen affinity could be found, and erythropoietin levels were inappropriately high for the hematocrit. The use of androgens, such as testosterone, can be associated with polycythemia.
Androgens stimulate erythropoietin production by the kidney.
The hematocrit elevation is usually mild, and the hematocrit returns to normal two to three months after discontinuance of anabolic steroid use. A similar increase in hematocrit can be achieved with erythropoietin injections. There is speculation that the sudden death of a number of competitive bicyclists between 1987 and 1990 was related to erythropoietin abuse. The unmonitored increase in red blood cell production may cause significant polycythemia, which, when coupled with exercise-induced dehydration, can result in tragic consequences. This use of erythropoietin is unethical, hazardous, and forbidden by the International Olympic Committee.