RESUMO
Background: Gender-affirming hormone therapy with either estradiol or testosterone for transgender persons can significantly impact chemistry and hematology laboratory tests. The sex used for assignment of reference intervals (RIs) in the electronic health record (EHR) will influence normal/abnormal flagging of test results. Objective: To analyze common non-hormonal laboratory tests with sex-specific RIs ordered in patients with sexual orientation/gender identify (SOGI) field differences (one or more differences between legal sex, sex assigned at birth, and gender identity) in the EHR at an academic medical center in midwestern United States. Methods: We utilized a previously characterized data set of patients at our institution that included chart review information on gender identity and gender-affirming therapy. We focused on the subset of these patients that had orders for 18 common laboratory tests in calendar year 2021. Results: A total of 1336 patients with SOGI field differences (1218 or 91.2% identifying as gender-expansive; 892 or 66.8% receiving estradiol or testosterone as gender-affirming therapy) had a total of 9374 orders for 18 laboratory tests with sex-specific RIs. Hemoglobin, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and high-density lipoprotein were the most frequently ordered tests. For patients taking estradiol, 128 of 970 (13.2%) creatinine and 39 of 193 (20.2%) hemoglobin measurements were within the RI for one sex but not the other. For those taking testosterone, 119 of 531 (22.4%) creatinine and 49 of 120 (40.8%) hemoglobin measurements were within the RI for one sex but not the other. Values above the cisgender female RI but within the cisgender male RI were common for hemoglobin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in patients taking testosterone. Conclusions: Clinicians should be aware of the potential impact of gender-affirming therapy on laboratory tests and what sex/gender is being used in the EHR to assign RIs.
RESUMO
Background: Gender-diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors. Methods: In two SPARK samples, we tested for associations of 16 polygenic scores (PGSs) with quantitative measures of gender diversity and mental health. In study 1, 639 independent adults (59% autistic) reported their mental health with the Adult Self-Report and their gender diversity with the Gender Self-Report (GSR). The GSR has 2 dimensions: binary (degree of identification with the gender opposite that implied by sex designated at birth) and nonbinary (degree of identification with a gender that is neither male nor female). In study 2 (N = 5165), we used a categorical measure of gender identity. Results: In study 1, neuropsychiatric PGSs were positively associated with Adult Self-Report scores: externalizing was positively associated with the attention-deficit/hyperactivity disorder PGS (ß = 0.10 [0.03-0.17]), and internalizing was positively associated with the PGSs for depression (ß = 0.07 [0-0.14]) and neuroticism (ß = 0.10 [0.03-0.17]). Interestingly, GSR scores were not significantly associated with any neuropsychiatric PGS. However, GSR nonbinary was positively associated with the cognitive performance PGS (ß = 0.11 [0.05-0.18]), with the effect size comparable in magnitude to the associations of the neuropsychiatric PGSs with the Adult Self-Report. Additionally, GSR binary was positively associated with the nonheterosexual sexual behavior PGS (ß = 0.07 [0-0.14]). In study 2, the cognitive performance PGS effect replicated; transgender and nonbinary individuals had higher PGSs (t316 = 4.16). Conclusions: We showed that while gender diversity is phenotypically positively associated with mental health problems, the strongest PGS associations with gender diversity were with the cognitive performance PGS, not the neuropsychiatric PGSs.
This research explores the connection between gender diversity, mental health, and genetic factors. It reveals that gender-diverse individuals often experience more mental health issues. Interestingly, rather than finding evidence linking these mental health challenges to genetic risk factors, the study discovered a replicable positive correlation between gender diversity and genetic markers for higher cognitive performance. This suggests that gender-diverse individuals typically have more of these cognitive performance gene variants. Finally, the study presents some early evidence suggesting that interactions between the environment (e.g., stigma) and genetic risk explain some of the elevated risk to mental health in gender-diverse individuals.