Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States - Scorecard - MDSpire

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States

  • By

  • Aaron L Misakian

  • Carly E Kelley

  • Erika A Sullivan

  • Julia J Chang

  • Gagandeep Singh

  • Sarah Kokosa

  • Jonathan Avila

  • Holly Cooper

  • Jane W Liang

  • Bren Botzheim

  • Meg Quint

  • Athavi Jeevananthan

  • Ellenor Chi

  • Madison Harmer

  • Laurel Hiatt

  • Michaela Kowalewski

  • Benjamin Steinberg

  • Telisha Tausinga

  • Hannah Tanner

  • Tiffany F Ho

  • Bayarmaa Mark

  • Brian Zenger

  • Sophia Hu

  • Amanuail Gebregzabheir

  • Justin M Penny

  • Danielle F Loeb

  • Tyler Strickland

  • Sean J Iwamoto

  • Micol S Rothman

  • Ole-Petter R Hamnvik

  • Danit Ariel

  • January 11, 2025

  • 0 min

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Clinical Scorecard: Administration of Injectable Estradiol in Transgender and Gender-Diverse Populations Across the United States

At a Glance

CategoryDetail
ConditionUse of injectable estradiol esters for gender-affirming hormone therapy in transgender and gender-diverse adults designated male at birth
Key MechanismsEstradiol esters (valerate and cypionate) administered IM or SC form microcrystalline depots releasing estradiol slowly to achieve desired serum concentrations
Target PopulationTransgender and gender-diverse adults designated male at birth receiving injectable estradiol for gender-affirming hormone therapy
Care SettingAcademic medical centers across the United States providing gender-affirming care

Key Highlights

  • Median estradiol dose to reach guideline-recommended concentrations when injecting every 7 days was 4.0 mg (IQR 3.0-5.0 mg).
  • Majority of patients reached supraphysiologic estradiol concentrations (>200 pg/mL) with current dosing.
  • No significant differences in estradiol concentrations or dosing between intramuscular and subcutaneous routes or between estradiol valerate and cypionate esters.

Guideline-Based Recommendations

Diagnosis

  • Serum estradiol concentrations should be interpreted relative to timing of last injection.
  • No current consensus on optimal timing for estradiol concentration measurement in injectable therapy.

Management

  • Injectable estradiol esters (valerate and cypionate) can be dosed lower than previously recommended to achieve target estradiol levels.
  • Dosing intervals typically every 7 or 14 days; dosing ranges vary widely in guidelines (2.0-10.0 mg IM every 7 days or 5.0-30.0 mg IM every 14 days).
  • Route of administration (IM vs SC) and ester type (EV vs EC) do not require dose adjustment.

Monitoring & Follow-up

  • Monitor serum estradiol concentrations considering timing post-injection to avoid misinterpretation.
  • Serum testosterone concentrations are typically checked mid-cycle; no specific recommendations exist for estradiol timing.

Risks

  • Supraphysiologic estradiol concentrations may increase risk of thromboembolic disease, liver dysfunction, and hypertension.
  • Providers should be cautious of excessively high estradiol levels with current dosing guidelines.

Patient & Prescribing Data

562 transgender and gender-diverse adults on stable injectable estradiol dosing for over 75 days across 6 US centers.

Lower doses than previously recommended effectively achieve guideline estradiol concentrations; timing and dose significantly influence serum levels; no difference between IM and SC or between EV and EC.

Clinical Best Practices

  • Interpret estradiol serum levels in context of timing since last injection to guide dosing adjustments.
  • Consider starting with lower injectable estradiol doses (around 4 mg weekly) to minimize supraphysiologic levels.
  • Route of administration (IM or SC) and choice of estradiol ester (valerate or cypionate) can be based on patient preference and availability without dose modification.
  • Regular monitoring for potential adverse effects associated with high estradiol concentrations is recommended.

References

Original Source(s)

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States

  • by Aaron L Misakian, Carly E Kelley, Erika A Sullivan, Julia J Chang, Gagandeep Singh, Sarah Kokosa, Jonathan Avila, Holly Cooper, Jane W Liang, Bren Botzheim, Meg Quint, Athavi Jeevananthan, Ellenor Chi, Madison Harmer, Laurel Hiatt, Michaela Kowalewski, Benjamin Steinberg, Telisha Tausinga, Hannah Tanner, Tiffany F Ho, Bayarmaa Mark, Brian Zenger, Sophia Hu, Amanuail Gebregzabheir, Justin M Penny, Danielle F Loeb, Tyler Strickland, Sean J Iwamoto, Micol S Rothman, Ole-Petter R Hamnvik, Danit Ariel

  • January 11, 2025

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