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Updated: Sep 18, 2025

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies
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Estradiol Concentrations for Adequate Gender-Affirming Feminizing Therapy: A Systematic Review.

Gabrielle N Winston-McPherson1, Tiffany A Thomas2, Matthew D Krasowski3

  • 1Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.

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|June 24, 2025
PubMed
Summary

Current guidelines suggest a 100-200 pg/mL estradiol range for transgender women's hormone therapy. This review found no evidence that this range ensures adequate feminization or prevents adverse events.

Keywords:
estradiolfeminizing therapyreference intervaltherapeutic rangetransfemininetransgender women

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Area of Science:

  • Endocrinology
  • Gender-affirming care
  • Pharmacology

Background:

  • Current guidelines recommend serum estradiol concentrations of 100-200 pg/mL for transgender women undergoing feminizing hormone therapy (HT).
  • This range is intended to ensure adequate feminization and minimize risks associated with HT.

Purpose of the Study:

  • To systematically review evidence evaluating the recommended 100-200 pg/mL estradiol range for its association with feminizing sufficiency, insufficiency, testosterone suppression, or toxicity in transgender women.
  • To assess whether current guidelines for estradiol concentrations in gender-affirming hormone therapy are evidence-based.

Main Methods:

  • A systematic review was conducted using the Populations/Intervention/Comparator/Outcome model.
  • Searches of Embase, MEDLINE, and Web of Science databases (1999-2023) identified 49 studies.
  • Outcomes included indicators of therapeutic insufficiency, sufficiency, toxicity, and hormone concentration.

Main Results:

  • The review identified 49 studies meeting inclusion criteria.
  • No studies demonstrated that the 100-200 pg/mL estradiol range is associated with optimal feminizing outcomes.
  • Evidence did not show that this range effectively reduces adverse events.

Conclusions:

  • The current guideline range of 100-200 pg/mL for serum estradiol is not supported by evidence for indicating sufficient feminization in transgender women.
  • Further research is needed to establish optimal estradiol targets for gender-affirming hormone therapy.
  • Clinical practice may need to re-evaluate the reliance on this specific estradiol concentration range.