In April 2016, the Netherlands Pharmacovigilance Centre Lareb received a report of a 55-year-old FTM transgender patient who developed secondary polycythemia. He explained that 18 years ago he started with testosterone injections of 250 mg once every 2 weeks. As desired, this resulted in cessation of menstruation, voice deepening, increase of muscle volume, and hair growth according to the male pattern. After a year, the dosage was reduced to 250 mg once every 3 weeks, but unfortunately this dosage appeared to be insufficient. Over the years, he used various testosterone preparations (e.g., testosterone gel, testosterone injections of 100 mg weekly and injections of 1000 mg once every 12 weeks).
Approximately a year after start of the testosterone therapy, the patient’s hemoglobin and hematocrit values started to increase. A few years later, his hemoglobin value slightly exceeded 11 mmol/L (reference range 8.5–11.0 mmol/L). Another 4 years later, his hemoglobin value was 11.5 mmol/L and hematocrit was 53% (reference range 40–50%). Besides the elevated hemoglobin and hematocrit, the erythrocytes were microcytic and had an abnormal morphology. The Janus kinase 2 (JAK2) mutation was negative (both exon 12 and 14), and therefore his hematologist considered primary polycythemia (polycythemia vera) to be highly unlikely.
Approximately 13 years after the start of hormonal therapy, the patient started treatment with an anticoagulant, acetylsalicylic acid in a dosage of 80 mg daily, and phlebotomy for the polycythemia. The patient’s hemoglobin value at that point was 11.7 mmol/L and the hematocrit value was 53%. However, this therapy caused a decreased iron count, fatigue, and sensitivity to developing furuncles. Regarding the latter, iron is essential for normal functioning of the immune system—the susceptibility to infection is increased by iron deficiency [5, 6].
Approximately 5 months after initiation of the anticoagulant and phlebotomy, the patient’s hemoglobin value decreased to 8.1 mmol/L and the hematocrit value decreased to 43%. The patient continued the testosterone therapy, anticoagulant, and phlebotomy. Except for a few abnormal values, the hemoglobin and hematocrit values have been within the normal range since then. The patient is now in an acceptable equilibrium with less frequent phlebotomy treatments and he uses a small amount of iron supplementation if his iron becomes too low for his well-being.
The patient reported this ADR at the Netherlands Pharmacovigilance Centre Lareb to raise awareness of the possible severity and impact of this ADR. The causality of the report was determined with a Naranjo assessment. Since polycythemia is a known adverse event, other possible causes were excluded, and the symptoms appeared after start of the testosterone, a Naranjo score of 6 was obtained. This Naranjo score indicates a probable relationship between the patient’s polycythemia and the use of testosterone.
Polycythemia is a known common ADR of testosterone therapy but is usually mild in nature [7, 8]. It is important that patients who are planning to start hormonal therapy are aware of this possible ADR.