Follow-up of a Cohort of Patients with Secondary Erythrocytosis Due to Testosterone Treatment
Authors: Flores-Moran Marie Solange , Cornejo Marina , Pedraza Alexandra , Sanz Cristina 
Published: December 2024

Introduction

Erythrocytosis occurs in 5-66% of patients receiving testosterone, and is the main reason for dose adjustment. The exact mechanism by which it develops is not fully understood. Up-to-date main hypotheses include hepcidin suppression independent of the erythroferrone pathway and indirect stimulation of the bone marrow. Currently, the most common reasons for using this treatment include hypogonadism and gender transition.

Objective

The aim of the present study was to describe the characteristics, treatment, and evolution of a series of patients with erythrocytosis secondary to testosterone treatment.

Methods

We retrospective studied 512 patients diagnosed with polycythemia between February 2000 and May 2024 in a single tertiary academic center. The diagnosis of polycythemia was made in the presence of hemoglobin (Hb) &gt;16.5g/dL. Patients included were under testosterone therapy, other causes of polycythemia were excluded. The patients were treated with phlebotomies or erythroapheresis.

Results

Of the 512 patients meeting polycythemia criteria, 29 patients (5.6%) had polycythemia secondary to testosterone therapy. The median age at diagnosis was 53 years [interquartile range (IQR) 40 - 64]. The causes for testosterone use were: 12 hypogonadotropic hypogonadism (41.3%), 9 hypergonadotropic hypogonadism (31%) and 8 transgender men (27.7%). According to the type of androgen: 15 received testosterone cyclopentylpropionate (51.7%), 11 testosterone undecanoate (37.9%) and 3 testosterone gel (10.3%). The median Hb and hematocrit at diagnosis were 18.5g/dL (IQR 18-19.5) and 57% (IQR 55-59), respectively. Erythropoietin was available in 26 patients; the median was within the normal range (8, IQR 6.3-13). None patient had JAK2 mutation. Seven patients had an abnormal spirometry (24.1%). Seven were diagnosed with sleep apnea-hypopnea syndrome (24.1%). In terms of cardiovascular risk factors, 16 patients were smokers (55.2%), 14 were obese (body mass index (BMI) &gt;30) (48.3%), 12 had hypertension (41.4%), 8 had dyslipidemia (27.6%), 4 had heart disease (13.8%), and 4 were diabetic (13.8%).

The median number of therapeutic procedures per patient was 8 (IQR 4-12), with 157 being erythroapheresis (60.6%) and 102 phlebotomies (39.4%). The most common adverse effects related to the procedures were: 4 extravasations (1.5%), 4 dizziness episodes (1.5%), and 1 paresthesia episode (0.4%). Nine patients (31%) were discharged after a median of 3 years (range 0-15).

Before the diagnosis of polycythemia and while on testosterone treatment, 3 patients had a thrombotic episode. After diagnosis, 3 patients experienced thrombotic events: 1 ischemia in a lower limb in a patient with chronic vasculopathy, 2 transient ischemic attacks in one patient, and 1 patient with superficial venous thrombosis in a lower limb and 1 cardioembolic ischemic stroke associated with atrial fibrillation. These three patients were using different types of testosterone, two were obese, and the events occurred &gt;5 years after starting testosterone. The six patients who had a thrombosis had at least 1 cardiovascular risk factor, median age 63 years (IQR 52.3-64.5), BMI 30 (IQR 25.9-33.8), and the use of testosterone was secondary to hypogonadism. No patient died during follow-up. The median follow-up duration was 3 years (IQR 2.2-8.8 or range 0-24).

Conclusions

In testosterone-induced polycythemia, erythropoietin does not appear to be involved in the mechanism of action. These patients have a high rate of thrombotic events, so it is important to maintain a good hematocrit level and effectively treat comorbidities.