In December 2025, Do No Harm co-signed a citizen petition asking the Food and Drug Administration (FDA) to address the risks of the widespread off-label prescription of estrogen to males for the purpose of so-called “gender-affirming care.”
The petition urged the FDA to open a dedicated docket to evaluate the safety and effectiveness of this off-label estrogen use in males and to convene a Part 15 public hearing to gather expert and patient testimonies on its risks and benefits, along with other safety measures.
Now, this week, Do No Harm submitted a comment on the citizen petition reaffirming the dangers of off-label estrogen use in males and reiterating calls for the FDA to take action through a public hearing.
“The evidence from both the literature and clinical practice shows that the risks associated with estrogen use in natal males are well-documented and significant,” the comment states. “Physicians prescribing estrogen and males receiving estrogen must be fully informed of these potential adverse effects.”
“Unfortunately, current labeling for estrogen-containing products does not adequately warn clinicians or patients about the dangers associated with this off-label use, undermining informed consent and patient safety,” the comment continues.
The comment additionally urges the FDA to take up the citizen’s petitions recommendations to (1) mandate a boxed warning on all relevant estrogen-containing products detailing the severe risks associated with their off-label use in males, (2) conduct a comprehensive safety review, and (3) mandate enhanced adverse event reporting to guide clinicians to report any serious adverse events the drugs create for patients.
