Diagnosis, management, and outcomes of drug-induced erythrocytosis: a systematic review

Abstract Secondary erythrocytosis refers to an elevation in hemoglobin or hematocrit due to elevated serum erythropoietin levels. Medications including testosterone and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are increasingly recognized as causes of secondary erythrocytosis. We conducted a systematic review to inform the clinical management of drug-induced erythrocytosis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search in MEDLINE, EMBASE, CENTRAL (all via Ovid), and Google Scholar. Of the 2036 articles screened for eligibility, 45 studies were included in our review, with 35 studies on testosterone and other androgen use, 5 studies on SGLT-2 inhibitors, 3 studies on antiangiogenic tyrosine kinase inhibitors (TKIs), 1 study on erythropoiesis-stimulating agents, and 1 study on a treatment regimen for multidrug-resistant tuberculosis. Cisgender and transgender men on prescription testosterone had erythrocytosis rates of up to 66.7%, with intramuscular formulations, higher doses, and older age associated with increased risk of erythrocytosis. Up to 2.7% of men on testosterone therapy developed thromboembolic events. Among individuals on SGLT-2 inhibitors, erythrocytosis rates ranged from 2.1% to 22%, with those who discontinued therapy demonstrating improvement or resolution of erythrocytosis. Thromboembolic events were reported in up to 10% of these individuals. Antiangiogenic TKIs were studied in patients with cancer, with erythrocytosis developing in up to 43.5% of patients. Drug-induced erythrocytosis is a heterogeneous condition for which there is no clear consensus among clinicians about its diagnosis and management. We offer recommendations for clinical practice within the scope of this systematic review, although further research is required.