Erratum: Injectable Estradiol Use in Transgender and Gender-diverse Populations

Overview

A correction was issued regarding data on testosterone suppression and estradiol concentrations in patients using injectable estradiol monotherapy. The corrected data clarify that only 21.6% of patients achieved both testosterone suppression and guideline-recommended estradiol levels without antiandrogens, highlighting gaps in current understanding.

Background

Injectable estradiol is commonly used in transgender and gender-diverse populations for feminizing hormone therapy. Achieving adequate testosterone suppression alongside physiologic estradiol levels is critical for effective treatment. Previous reports suggested challenges in balancing estradiol dosing and testosterone suppression without antiandrogens, with concerns about potential side effects at supraphysiologic estradiol levels.

Data Highlights

In a cohort of 88 patients with intact gonads injecting estradiol every 7 days, 19 (21.6%) achieved both testosterone suppression (<50 ng/dL) and estradiol concentrations within the guideline-recommended range (100-200 pg/mL) without concurrent antiandrogen or GnRHa use. The testosterone suppression status of the remaining 69 patients without antiandrogens remains unclear.

Key Findings

• Only 21.6% of patients on injectable estradiol monotherapy reached both testosterone suppression and guideline estradiol levels.
• These patients did not use concurrent antiandrogens or GnRHa.
• The majority (78.4%) did not achieve testosterone suppression without additional medications.
• Previous interpretations suggesting forced choice between antiandrogen side effects or supraphysiologic estradiol risks were corrected.
• Further research is needed to understand estradiol monotherapy efficacy in testosterone suppression.

Clinical Implications

Clinicians should recognize that injectable estradiol monotherapy may not reliably suppress testosterone in most patients without adjunctive antiandrogens. Careful monitoring of hormone levels remains essential, and individualized treatment plans may be necessary. Additional studies are warranted to optimize hormone regimens balancing efficacy and safety.

Conclusion

The correction clarifies that only a minority of patients achieve both testosterone suppression and physiologic estradiol levels with injectable estradiol alone, underscoring the need for further investigation into hormone therapy strategies in transgender care.

References

1. Milano C and Harper J 2026 -- Discussion on the Use of Injectable Estradiol in Transgender and Gender-diverse Populations in the U.S.