Gender Minority Stress, Support, and Inflammation in Transgender and Gender-Nonconforming Youth

Abstract

Purpose: Transgender and gender-nonconforming (TGNC) youth often report higher rates of chronic social stressors such as victimization, discrimination, and rejection. Some of these gender-based stressors may have long-range physical health consequences through inflammation pathways. This study evaluates the feasibility and acceptability of adding biological measures of inflammation to an ongoing prospective clinical study of TGNC youth (ages 9–20 years), initiating affirming medical therapy at a large, urban children's hospital (N=56). We also examine the relationship between gender-based sources of stress and support with inflammation. This is the first study to explore how gender identity, social stressors, and social supports may contribute to poorer health in TGNC youth through inflammation and immune dysregulation pathways.

Methods: Between October 2016 and August 2018, the study team collected dried blood spot (DBS) samples and health measures during clinical visits. Participants also completed computer-assisted surveys assessing gender minority stress and support during these visits. We used regression analysis to evaluate differences in C-reactive protein (CRP) controlling for demographics, health, gender-based stress, and supports.

Results: The results from this study indicate that adding DBS samples to assess inflammation was feasible and acceptable in a clinical sample of TGNC youth seeking affirming-medical interventions. We found an association between greater inflammation and the composite score for greater gender-based stressors and lower gender-based supports using the Gender Minority Stress and Resilience Tool (GMSR); however, we did not find statistically significant differences in CRP associated with any of the individual GMSR subscales assessing various types of gender-based supports or stressors.

Conclusion: More research is necessary to evaluate how different sources of gender-based support and stress relate to inflammation with larger sample sizes.

Introduction

Transgender and gender-nonconforming (TGNC) people consistently report higher social stress compared to their cisgender counterparts.^1,2 With the onset of puberty, TGNC youth often face additional stress caused by bodily changes and increased scrutiny by peers, family, and even strangers, attempting to “police” their gender.^2,3 Both these sources of stress, in turn, contribute to risky health behaviors, mental illness, and, potentially, physical illnesses.^1,2,4 Similar chronic, identity-based stress during adolescence contributes to poorer physical health trajectories through inflammation pathways in other marginalized populations.^5–8 However, this relationship remains relatively unexplored in TGNC youth. In addition, the authors are unaware of clinical studies with TGNC youth examining the feasibility of adding dried blood spot (DBS) samples to measure inflammation.

Gender-based sources of stress and support

The minority stress theory, the prevailing model of how stress influences gender minority health, primarily addresses mental health outcomes.^9,10 In this theoretical framework, TGNC youth experience marginalization based on their gender through proximal and distal stress processes. Proximal processes include internalized transphobia, expectations of negative future events, and concealment of one's gender identity. Past interactions between the individual and the environment contribute to proximal processes, but they occur internally. Distal stress processes include social and structural processes in the broader environment, including discrimination and nonaffirmation of gender identities.

While these minority stress processes have negative mental health consequences, TGNC youth may also access unique social supports and coping mechanisms because of their gender identity. Singh et al. propose that community connections, embracing your identity, and self-worth are among the most important tools in promoting resiliency among TGNC youth.^11–15 Similarly, community belonging and social support have been associated with better mental health in TGNC populations,^14–18 and the broader association between physical health and community connectedness is a well-established relationship.^19–21 Pride in minority identities has also been shown to buffer the influence of stress on mental health.^22,23 Assessing both gender-based sources of stress and support provides a more comprehensive picture of the social contexts for TGNC youth.

Minority stress and support may influence inflammation

A positive relationship between identity-based social stressors and inflammation has been shown in a number of other marginalized populations,^7,24–26 but is yet to be studied specifically in TGNC youth. While increased inflammation in response to acute stressors is adaptive, chronic exposure to psychosocial stressors is associated with a sustained upregulation of inflammation.^27–29 A growing literature links persistently high levels of inflammation, such as the inflammatory marker C-reactive protein (CRP), to a host of physical health risks, including cardiovascular disease, obesity, cancer progression, and diabetes. Compared to adults, chronic identity-based stress during adolescence has an even greater potential to cause harm because adolescence is a sensitive period for the development of stress physiology.^6,28,30 Exposure to social stressors during this critical stage can be even more consequential to the long-term physical health risks associated with inflammation compared to similar stress exposure in adults.³¹ For this reason, assessing biomarkers of stress provides additional information about future health trajectories before clinical health problems manifest. In addition, CRP levels are one of the more commonly used tests for inflammation ordered by clinicians,³² but researchers have yet to examine these inflammatory markers in younger patients seeking gender-affirmative care.³³

The lack of research investigating gender-based stressors and support led to this exploratory study. The goal of the study was to, first, consider the feasibility and acceptability of collecting DBS samples to assess inflammation in a clinical sample of 50 American transgender youth. We hypothesized that it would be feasible and acceptable to add DBS samples to an existing study about affirming medical interventions for TGNC youth. Second, this study is one of the first articles to investigate the relationship between CRP, gender-based stress, supports, and other health indicators (e.g., body mass index [BMI]). To our knowledge, there is only one published study examining the relationship between identity-based stressors and inflammation in adult transgender men³⁴ and no studies published on stress regulation in transgender women or transgender youth, as this study will include. Because greater identity-based stressors have been associated with greater inflammation, the authors hypothesized that greater gender-based stressors and less identity-based support would be positively associated with greater inflammation.

Methods

The current study was a substudy of a multisite, longitudinal, NIH-funded cohort study of medical interventions for TGNC youth under award #R01HD082554. The site for this substudy was a large Midwestern Children's Hospital with a gender development program, and we used data from baseline visits for the cross-sectional analysis.

Participants

This clinical sample consisted of self-identified TGNC youth ranging in age from 9 to 20 years. All participants received medical treatment at the study site's gender development clinic. The researchers recruited all participants directly from a larger parent study concerning gender-affirming treatments for transgender youth. Researchers obtained informed consent from participants and their parents or legal guardians for the substudy at the same time as the parent study. The research team enrolled 59 out of the eligible 101 participants from the parent study between September 2016 and August 2018. The research team discussed reasons for not enrolling in the study with eligible participants of the parent study and tracked issues during the data collection process.

Table 1 describes the demographic composition of participants. Of the 59 participants enrolled, we excluded nine. Five participants did not have viable DBS samples to assay. Two participants had raw CRP values over 5 mg/L in the baseline wave of data and not in the second wave of DBS collection 6 months later. This acute increase in relative CRP levels found only at baseline indicated that they were ill (e.g., common cold) at the baseline visit. Because the goal of the study was to assess chronic inflammation, not the acute inflammation present with a temporary illness, we excluded these two participants from the analysis. Two participants identified as gender-fluid/nonbinary. This group lacked statistical power for the analysis so we also excluded these two observations. Fifty participants composed the final analytic sample.

Table 1.

Demographic Descriptive Statistics and Test Statistics for Differences by Gender Identity

	Total		Female/transgender female		Male/transgender male			Test statistics
	N	%	N	%	N	%	X2	p	Fishers exact
Race
White	35	70	7	14	28	56	1.676	0.433	0.448
Hispanic/Latinx	8	16	2	4	6	12
Other	7	14	3	6	4	8
Living arrangement				22		62
Parent's house or apartment	42	84	11	2	31	10	0.919	0.632	1
Family member's house or apartment	6	12	1	0	5	4
Own house or apartment	2	4	0	14	2	56
Tanner stage
Two	2	4	2	17	0	0	29.700	0.319	0.395
Three	3	6	1	8	2	5
Four	2	4	1	8	1	3
Five	43	86	8	67	35	92
	N	M (SD)/%	N	M (SD)/%	N	M (SD)/%	t	df	p
Family socioeconomic status
Highest parent's ed. (years)	50	15.53 (2.81)	12	14.71 (3.91)	38	15.79 (2.37)	−1.166	48	0.250
Family received government benefits	50	20%	12	17%	38	21%	−0.325	48	0.747
Age (years)	50	15.78 (1.90)	12	15.67 (2.02)	38	15.82 (1.89)	−0.235	48	0.815
BMI (kg/m2)	50	25.44 (6.51)	12	23.10 (4.62)	38	26.18 (6.88)	−1.444	48	0.155
Any tobacco use (%)	13	28%	3	0.27	10	28%	−0.032	48	0.975
Depression (BDI-Y 20)	50	14.16 (11.27)	12	13.55	38	14.35	−0.211	48	0.834
CRP (mg/L)a	50	1.08 (1.67)	12	0.84 (1.61)	38	1.16 (1.71)	−1.648	48	0.106

^aPlasma equivalent values.

BDI-Y, Beck Depression Inventory-Youth; BMI, body mass index; CRP, C-reactive protein; SD, standard deviation.

Procedures

Clinicians completed a prescreening worksheet and reviewed medical records to assess eligibility for the parent study. Inclusion criteria for this study and the parent study included a clinical assessment of Tanner stage, a clinical assessment of the presence of gender dysphoria, receiving or planning to receive services at the study site's clinic, and ability to provide informed consent. Participants were excluded from participation based on the inability to read/understand English or if they had preexisting osteoporosis. The pediatric clinical team also assessed inclusion criteria related to participants' ability to provide informed consent or complete the Audio Computer-Assisted Self-Interview (ACASI), and the study team excluded participants that exhibited serious psychiatric symptoms (e.g., active hallucinations and thought disorder), being visibly distraught (e.g., suicidal, homicidal, and exhibiting violent behavior), and being under the influence of substances. The research team obtained parental consent along with minor assent for those under 18, while participants over the age of 18 provided consent.

The study data were derived from surveys, health records, and assays of DBS samples. Participants completed a series of questionnaires using an ACASI, including measures evaluating gender-based stress, gender-based support, health-related quality of life, tobacco use, depression, and demographics. Medical records provided objective health measures (height, weight) and clinical assessments of illnesses. After training, the research team collected DBS samples during the clinical visit to assess CRP using a previously validated protocol for DBS samples.³⁵

The study team also collected qualitative data about enrollment and as issues arose with data collection. In April 2017, the study team increased compensation for participants' time and effort. Participants received $100 for participating in the parent study and an additional $20 (September 2016 to March 2017) or $25 (after April 2017) for the time and effort related to the collection of the DBS sample. We also implemented several changes to resolve dehydration and blood flow issues at this time. The Institutional Review Board at Ann and Robert H. Lurie Children's Hospital of Chicago and Northwestern University reviewed and approved the study methods.

Measures

Gender identity

The ACASI included the following gender identity item: How do you currently identify in terms of your affirmed gender? Participants could select from 10 options. These options included the six reported in this study: male, female, transgender female, transgender male, gender-fluid, and genderqueer. They also could respond to the prompt, “In what other way do you currently identify in terms of your affirmed gender? Please specify.”

Demographics

The ACASI incorporated a set of standard demographic questions, including age, race, assigned sex at birth, living situation, and parents'/guardians' educational attainment.

Gender Minority Stress and Resilience Tool

The ACASI included the Gender Minority Stress and Resilience Tool (GMSR), a measure validated for use with adolescent and adult samples,^36–38 to evaluate stressors and sources of support related to gender identity. Consistent with the parent study, we used six of the nine constructs in the GMSR: nondisclosure of gender identity (e.g., because of my gender identity/history, I avoid exposing my body); nonaffirmation; negative expectations of the future because of their gender identity (e.g., if I express my gender identity/history, others wouldn't accept me); internalized transphobia; pride in their gender identity; and community connectedness to others sharing their gender identity (e.g., I feel connected to other people who share my gender identity). These constructs used a four-point Likert scale to assess agreement with prompts ranging from 1 “strongly disagree” to 5 “strongly agree.”

BMI and current health status

The study team used medical records and surveys included in the ACASI to assess physical health status. Clinical staff collected anthropometric measures during the clinical visit, including the height and weight used to calculate BMI (kg/m²) and the sexual maturity assessment used to determine Tanner stage. Because the baseline visit occurred before gender-affirming medical intervention, we defined overweight and obesity status using BMI parameters for participants' natal sex and age. Clinicians recorded participants' responses to questions regarding medications and current health issues. The Beck Depression Inventory-Youth (BDI-Y) is a validated, 20-item tool for youth to assess depression symptoms (i.e., behaviors, thoughts, and feelings youth have had in the last 2 weeks).³⁹ The Alcohol, Smoking and Substance Involvement Screen Test (ASSIST) captured any tobacco use.⁴⁰

C-reactive protein

The research team collected DBS samples as part of the clinical visit. We logged, recorded, and stored DBS samples at −30°C after collection from the participant. We then assayed samples at the Northwestern University's Laboratory for Human Biology Research using enzyme-linked immunosorbent assay protocols to produce concentrations of CRP (mg/L).^35,41,42 Raw values of CRP from the assays were converted to plasma-equivalent values and log-transformed before statistical analyses.

Data analysis plan

First, the research team hypothesized that participants participating in a larger clinical study would find adding DBSs to assess inflammation acceptable. To examine this study aim, we evaluated the frequency of participants enrolling in the substudy from the parent study before and after changes in the recruitment and DBS data collection strategy. We also explored reasons participants provided for not enrolling in this study and describe factors contributing to a smaller analytic sample.

Second, because past research has demonstrated a positive relationship between greater identity-based stressors and CRP,^43–45 we hypothesized that greater gender identity-based stress and lower social support would be associated with higher relative levels of CRP. The initial analysis consisted of descriptive statistics, followed by bivariate tests of association (i.e., t-tests and Fisher's exact statistic) to examine differences in demographics and health by gender. Next, we used multiple regression analyses to inspect the associations between gender-based stressors, supports, and CRP. The final regression models control for potentially confounding variables influencing inflammation, including gender (1=male/transgender male, 0=female/transgender female), years of age, Tanner stage (1=Tanner Stages 4 or 5, Tanner Stages 2 or 3=0), race (recoded white=1, other=0), tobacco use (any=1, none=0), continuous BDI-Y depression score, and BMI. We performed mean-imputation for missing values of two predictor variables: tobacco use (6%, n=3) and depression (12%, n=6). As a sensitivity analysis, we fitted models on nonimputed data. This resulted in similar point estimates and significance. In all analyses, we used the a priori p-value of 0.05 as the criterion for statistical significance and Stata/SE 14.2 for Mac for data analysis.

Results

Feasibility and acceptability

For the first research question, we found that it was feasible and acceptable to collect DBS samples in a clinical sample of TGNC youth seeking affirming-medical interventions; however, the research team did encounter challenges contributing to enrollment and overall sample size. Of the 101 participants recruited for the parent study during the same period, 59 (58%) enrolled in this study. Participants self-reported fear of the finger prick as the main reason for not enrolling in the substudy. After 6 months of recruitment, we increased participant compensation for time and effort to $25 from $20 in April 2017. After increasing participant compensation by $5, the enrollment rate increased from 51% to 66%.

Additional issues contributed to decreasing the analytic sample from 59 to 50 participants. First, the research team could not obtain a DBS sample sufficient in size or volume to analyze for five participants (7%). Heavily calloused hands, dehydration, and slow blood flow impeded DBS collection for these participants. To address these issues, clinicians provided participants with a bottle of water to offset potential dehydration. The research team also asked participants to rub their hands together and put their hands under warm water to increase blood flow before the finger prick.

Second, we excluded two participants (3%) from the analysis because we determined that they were ill during the clinical visit. For these two participants, the DBS analysis yielded relative raw values of CRP above 5.0 for only the baseline clinical visit used in this analysis, and much lower values within the relative curve for the subsequent clinical visit. These high CRP values suggested that the participants had acute inflammation due to a temporary illness (e.g., common cold and flu).

Third, two participants identified as nonbinary or gender-fluid. We excluded these two participants from the analytic sample because we lacked the statistical power to assess differences for these identities. The final analytic sample came to 50 participants or 85% of the 59 participants enrolled.

Descriptive analysis

Table 1 displays the total number of observations and means or percentages for the demographic and health variables. Participants with transmasculine identities, male or transgender male, composed 76% of the sample, and 24% of participants identified with transfeminine identities, female or transgender female. Sixteen years of age was the median age (standard deviation [SD]=1.89), and, on average, participants' parents or guardians received some college as their highest level of education. Seventy percent of the sample reported their race/ethnicity as white; 16% as Hispanic/Latinx; and 14% as another race or more than one race/ethnicity. Most of the participants (85%) lived with their parent(s), followed by 15% who lived with a family member, and 4% who lived in their own house or apartment. Half of the participants were overweight, and 34% were clinically obese. The majority of the participants were postpubertal in Tanner stage four (4%) and five (86%). Twenty-eight percent of the sample had ever used tobacco. The mean score on the BDI-Y was 14.16, just past the cutoff of 14 for mild depression. We did not find statistically significant differences in the demographics or health of participants across gender.

Regression analysis

In the regression analysis addressing the second objective of the study, we examined if there is a positive relationship between gender-based stressors and CRP and a negative relationship between gender-based supports and CRP. The multiple regression analyses presented in Table 2 displays the association between gender-based stressors and supports on CRP controlling for demographic and health covariates. We found no statistically significant differences in CRP across the six gender-based stressors and supports measured by the Gender Minority Stress and Resilience Tool using the a priori 0.05 threshold. However, we detected a statistically significant relationship between a higher composite score of the GMSR and greater inflammation (Model 7; β=0.351, p=0.050). Similarly, each year of age is associated with a significant increase in CRP (p<0.01). Our results also suggest a negative relationship between tobacco use (β=−0.612, p=0.046) and lower inflammation in Model 6, the community connectedness analysis, but no other models. Across all models, BMI contributed to a significant increase in relative CRP (p<0.001). In a separate analysis (not shown), we did not find that BMI mediated the relationships between stressors, supports, and CRP in any of the models.

Table 2.

Summary of Ordinary Least Squares Regression Analysis of Demographic, Health, Gender-Based Stress, and Support with C-Reactive Protein

	Model 1	Model 2	Model 3	Model 4	Model 5	Model 6	Model 7
Transmasculine	0.492 (0.335)	0.499 (0.327)	0.509 (0.415)	0.525 (0.322)	0.525 (0.336)	0.584 (0.335)	0.604 (0.325)
Age	0.287** (0.098)	0.301** (0.096)	0.297** (0.096)	0.303** (0.095)	0.295** (0.097)	0.306** (0.094)	0.308** (0.096)
Tanner Stage 4 or 5	−0.961 (0.569)	−1.078 (0.578)	−1.009 (0.574)	−0.996 (0.541)	−1.012 (0.587)	−1.055 (0.553)	−1.020 (0.533)
BMI	0.074*** (0.015)	0.079*** (0.015)	0.075*** (0.015)	0.076*** (0.015)	0.074*** (0.015)	0.076*** (0.01)	0.076*** (0.015)
Tobacco use	−0.556 (0.309)	−0.540 (0.299)	−0.552 (0.313)	−0.561 (0.304)	−0.561 (0.310)	−0.612* (0.298)	−0.599 (0.305)
Depression (BDI-Y)	0.007 (0.009)	0.011 (0.010)	0.006 (0.010)	0.009 (0.009)	0.007 (0.010)	0.011 (0.010)	0.015 (0.009)
Nondisclosure	−0.012 (0.018)
Negative expectations		−0.022 (0.013)
Nonaffirmation			−0.010 (0.033)
Internalized transphobia				−0.015 (0.013)
Pride					0.007 (0.017)
Community connectedness						0.046 (0.028)
GMSR composite							0.351* (0.174)
Constant	−6.310*** (1.322)	−6.344*** (1.230)	−6.443*** (1.277)	−6.596*** (1.238)	−6.669*** (1.405)	−7.455*** (1.424)	−6.983*** (1.298)
Observations	50	50	50	50	50	50	50
R2	0.485	0.504	0.483	0.491	0.485	0.509	0.511

All models use transmasculine participants, Tanner stages 4 or 5, and any tobacco use as the indicator variables. Age is in years. Raw values of CRP were converted to plasma-equivalents and log-transformed. Robust standard errors in parentheses.

^***p<0.001, ^**p<0.01, ^*p<0.05.

GMSR, Gender Minority Stress and Resilience Tool.

Discussion

This study represents an initial step toward a better understanding of factors related to if and how stress “gets under the skin” of TGNC youth. It is the first to do so with TGNC youth. The study demonstrates that it is feasible and acceptable to add a DBS protocol to an existing clinical study of TGNC youth to assess inflammation. However, we identified several challenges to recruitment over the 2-year enrollment period. By addressing a few concerns about dehydration, blood flow, and a small increase in participants' compensation ($5), we increased enrollment by 15%. Fear of the finger prick was the only reason provided for not enrolling in the study.

We found no statistically significant differences in CRP associated with gender-based supports or stressors when investigating the contributions of individual components of the GMSR. When we tested the composite score of the six GMSR scales, our results did suggest an association between greater gender-based stress and a lack of support with inflammation. The composite score of the GMSR subscales could be a stronger signal of the overall stress burden for transgender youth, whereas it is possible that the small sample size and variation of the subscales hindered detecting a statistical difference. The limited nature of the existing literature exploring gender-based stress and inflammation complicates the interpretation of these findings. DuBois found that greater CRP was associated with a gender-based stressor, stress about passing, in a sample of adult transgender men, but found no such relationship with stress about being “out.”³⁴ Future research should reproduce our analyses with larger samples, taking note of the procedural changes that contributed to greater participant recruitment and viable DBS samples. Researchers should explore these variations in the types of gender-based stress and support, global assessments of gender-based stress, and their relationship with inflammation. The implications of CRP on subclinical physical health outcomes should be considered in the overall research agenda specific to transgender health and medicine.

Several characteristics of this study's sample should be noted. We recruited from a clinical sample of TGNC youth engaged in a parent study. The nature of the parent study, assessing the influence of gender-affirming medical interventions on health and socioemotional outcomes, may have decreased the rate of gender-fluid and nonbinary youth available to enroll. Studies with the statistical power to examine differences across more gender identity categories have found that nonbinary youth report higher rates of stress compared to youth with binary identities.^46–48 The small number of participants identifying as nonbinary or gender-fluid in this study prohibited a statistical analysis of these identities, but future studies should address differences outside of a male–female binary.

As reported in other studies, the majority of our clinical sample self-identified as male or transgender male.^49,50 The smaller number of participants identifying as female or transgender female (n=12) compared to the number of male and transgender males participants (n=38) could account for some of the lack of significance in our regression models.

In addition, the ability to receive the gender-affirming medical intervention, a qualification of the parent study, may require some floor level of gender-based support. It is possible that youth in this sample had access to supports which other TGNC youth do not. Seventy percent of the sample identified as white, and most (84%) lived with their parents. According to the 2016 Census, 52% of American youth receive government assistance of some kind,⁵¹ but only 20% of our sample reported receiving government assistance. These demographic factors, in addition to having access to affirming medical interventions, indicate selection bias and could have influenced whether we were able to detect significant variation in relative CRP. Similarly, transgender people of color are more likely to experience homelessness, incarceration, victimization, and other social stressors compared to white transgender populations,^10,52,53 and access to care influences reported minority stress and its influence on physical health.⁵⁴ Given what is known about the relative status of the participants in this study, our estimates of gender-based stress and physical health study should be regarded as conservative.

While we controlled for several demographic and health indicators, additional health anomalies of this sample could have influenced inflammation. One important characteristic of this sample was the relatively high BMI of participants. Thirty-four percent of this sample was obese, but the parent study of four sites found that only 16% of TGNC youth were obese,⁵⁵ and the Centers for Disease Control and Prevention indicates that only 21% of American adolescents are obese.⁵⁶ With the well-established, direct causal relationship between body fat (proxied by BMI) and systemic inflammation (CRP),^28,57–59 the high frequency of obesity in this sample may have contributed to the lack of significant findings between subscales of stress, support, and inflammation. We did not find that BMI mediated the relationship between stressors, supports, and CRP in a separate analysis; however, the lack of statistical power may have contributed to these findings with our analytic sample of 50. Adding DBS samples to assess inflammation in larger, more representative studies could allow for a more thorough exploration of the mediational relationship of BMI and the independent effects of GMSR on inflammation. This is an important relationship to probe further as affirming hormone therapy also contributes to changes in BMI among TGNC populations.^60–62

Several other characteristics of the clinical sample may have contributed to the lack of significant findings between GMSR subscales and inflammation. The small study sample and small number of participants reporting that they had ever used any tobacco in their lifetime (n=13) also likely contributed to the significant relationship between tobacco use and lower CRP in model six, which runs counter to the existing literature.⁶³ Similarly, while estimates of American adolescents experiencing depression in the past year range from 9% to 13%,^64,65 43% of our participants meet the criteria for depression. Chodzen et al. reported a positive association between depression, anxiety, and gender-based stress in a similar sample of TGNC youth from the same Midwestern clinic,⁶⁶ and depression and anxiety have been associated with higher relative CRP in other populations.^26,45 However, we did not detect a statistically significant relationship between depression and CRP in this sample. Finally, while this study included participants ranging in age from 9 to 20 years, there was a low standard deviation in age (M=15.78 years, SD=1.90 years). These characteristics are important in contextualizing the study's results because age, obesity, tobacco use, and depression contribute to differences in gender-based stress, supports, and CRP.^{27,57,59,67–69} Researchers should replicate the analyses from this study with larger, more representative samples in future studies.

In summary, our results suggest that adding DBS samples to assess inflammation is feasible and acceptable among TGNC youth; however, the small sample size and characteristics of the sample contributed to issues in detecting relationships between gender-based stressors, supports, and inflammation. Clinicians, policymakers, and researchers alike should note that TGNC youth experience greater gender-based experiences of stress and different access to supports compared to their peers,^2,70,71 and greater exposure to gender-based stress may influence the health trajectories of TGNC youth.^66,72,73 Future research should follow-up with changes in the overall stress burden of TGNC youth, including biomarkers of stress such as CRP, to determine stress-related health trajectories.

Abbreviations Used

ACASI

Audio Computer-Assisted Self-Interview

BDI-Y

Beck Depression Inventory-Youth

BMI

body mass index

CRP

C-reactive protein

DBS

dried blood spot

GMSR

Gender Minority Stress and Resilience Tool

SD

standard deviation

TGNC

transgender and gender-nonconforming

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research was supported by The Northwestern University Pilot Research Initiatives in Developmental Sciences, Northwestern Society of Fellows, Ann & Robert H. Lurie Children's Hospital of Chicago's Gender & Sex Development Program, the National Academy of Education/Spencer Dissertation Fellowship, Northwestern University Graduate Research Grant, the Sexualities Project at Northwestern University, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (#R01HD082554).

Cite this article as: McQuillan MT, Kuhns ML, Miller AA, McDade T, Garofalo R (2021) Gender minority stress, support, and inflammation in transgender and gender-nonconforming youth, Transgender Health 6:2, 91–100, DOI: 10.1089/trgh.2020.0019.