Goldstein, Zil

Abstract Background The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine–specific recommendations in the United States for the gender-diverse population. Content This document outlines pathology- and laboratory medicine–specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following 5 topics: (a) reference intervals and interpretation of laboratory tests impacted by use of GAHT (testosterone for transgender men; estradiol with or without antiandrogens for transgender women), focusing on those stably on GAHT for 6 months or longer; (b) transfusion medicine considerations for the gender-diverse patient population, (c) consideration of gender diversity in autopsy and death investigation, (d) interpretation of histology from tissues that are impacted by GAHT and surgical procedures; and (e) pathology and laboratory medicine informatics challenges and opportunities. Summary A relatively small group of laboratory tests is significantly impacted by GAHT. The histology of some tissues shows changes attributable to GAHT or to nonhormonal medical procedures. Autopsy and transfusion medicine practices for the gender-diverse population currently lack standardization, although this is evolving. The landscape of pathology informatics related to gender diversity is complicated by varying electronic health record and laboratory informatics systems functionality.

Purpose: Guidelines recommend serum estradiol concentrations of 100–200 pg/mL for transgender women prescribed oral, subcutaneous, or transdermal estradiol with or without adjunct antiandrogen as gender-affirming feminizing hormone therapy (HT). The purpose of this systematic review was to evaluate if the guideline range of 100–200 pg/mL for estradiol concentration is associated with indicators of adequate gender-affirming feminizing HT, specifically feminizing sufficiency, insufficiency, testosterone suppression, or toxicity in transgender women. Methods: The Populations/Intervention/Comparator/Outcome model was applied to the study question, whereby the target population included transgender, gender-diverse, and nonbinary adults using gender-affirming feminizing HT by any route of administration, with or without adjunct antiandrogen use. The comparator was defined as estradiol concentrations within (100–200 pg/mL or 367–734 pM) versus outside (</>100–200 pg/mL) the guideline range; evaluated outcomes were listed by the same clinical guidelines that recommend using the 100–200 pg/mL range. Embase, MEDLINE, and Web of Science were queried over a 24-year time frame (January 1, 1999–April 20, 2023); the search was restricted to English. The extracted outcomes were categorized as indicators of therapeutic insufficiency, sufficiency, toxicity, or hormone concentration. Results: There were 49 studies that met the inclusion criteria, of which 9, 42, 25, and 5 studies included indicators of therapeutic insufficiency, sufficiency, toxicity, or hormone concentration, respectively. The search did not identify articles demonstrating that the 100–200 pg/mL guideline range provides optimal feminizing outcomes or reduces adverse events. Conclusions : Evidence does not support using the guideline range of 100–200 pg/mL to indicate sufficient feminization in transgender women using gender-affirming feminizing HT.