Mount Sinai Study Finds Testosterone Use in Transmasculine People Is Safer Than Previously Reported

Despite its widely accepted usage, testosterone treatment for gender-affirming hormone therapy (GAHT) in transmasculine individuals often conjures up safety concerns among prescribing physicians, and patients and their families. However, a comprehensive study by Mount Sinai’s Division of Endocrinology, Diabetes and Bone Disease, and the Center for Transgender Medicine and Surgery should afford them a new level of reassurance. In fact, the largest study of its type to date, published in November 2023 in the Journal of Clinical Endocrinology and Metabolism, found testosterone treatment to be safer than previous smaller studies have reported.

“It’s pretty common for providers, including endocrinologists, to cut back on testosterone in a transmasculine patient whose hematocrit is elevated,” says senior author Joshua Safer, MD, FACP, FACE, Executive Director of the Center for Transgender Medicine and Surgery, and Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai. “Our study should give them the comfort to do the right thing for the patient,” and address other explanations for high hematocrit unrelated to testosterone, “because we found that while higher testosterone levels were associated with higher hematocrit, the level was too small to be clinically meaningful for most patients.”

A long-held concern with exogenous testosterone is that it might overly stimulate red blood cells, potentially interfering with normal blood flow, as evidenced by changes in hematocrit—the ratio of the volume of red blood cells to the total volume of blood. Mount Sinai researchers learned that less than 1 percent of transmasculine people in their study had hematocrit greater than 54 percent, the level at which treatment for erythrocytosis is recommended, and only 8.4 percent had hematocrit greater than 50 percent. The cross-sectional analysis encompassed 6,670 transmasculine people who were prescribed testosterone for GAHT by Plume, a virtual provider of gender-affirming care across 45 states.

“Our hope is that this research will temper fears by clinicians who may be a little on edge about provisioning exogenous testosterone for gender-affirming hormone therapy in patients who desire it and would benefit from it,” says Daniel Slack, MD, a second-year endocrinology fellow at The Mount Sinai Hospital and co-author of the study. “We’re providing evidence-based reassurance to providers that this therapy is safe and that they shouldn’t be withholding it from their transmasculine patients simply out of fear of erythrocytosis.”

Past studies have shown rates of erythrocytosis in patients undergoing GAHT at slightly higher rates than those from the Mount Sinai study. “The reason may lie in the fact these studies used smaller cohorts that were not representative or that they reflected differences in patient populations,” Dr. Safer says. “Our study is the largest to date on the subject and, as such, demonstrates how we’re able to leverage the access we have to larger numbers of people treated here to deliver valuable guidance on safety and optimal treatment strategies to providers in the field.”

Part of the guidance to emerge from the latest study is the need to assess factors other than just testosterone that could potentially lead to erythrocytosis. “Our work suggests that providers also need to investigate such factors as obesity, tobacco smoking, and use of alcohol,” says Nithya Krishnamurthy, a second-year medical student at Icahn Mount Sinai and lead author of the study. “We know these risks can contribute to changes in blood profiles and adverse clinical outcomes, and physicians have a responsibility to address these lifestyle factors and comorbidities before withholding or reducing the use of testosterone.”

That thought is echoed by Dr. Slack, who will soon become a faculty member at Mount Sinai. “Transgender and gender-diverse individuals are growing in visibility around the world, and the endocrinologists, primary care doctors, and other specialists who treat them need to be well educated and informed about their unique needs,” he says. “Hopefully this study will provide an important addition to their clinical tool kit.”