Minority Stress in Relation to Biological Outcomes among Sexual and Gender Minority People: A Systematic Review and Update

Abstract

Here we present an updated systematic review identifying studies published 2019–2024, since our prior systematic review in 2020, that examine the association between minority stress and a biological outcome among sexual and gender minority (SGM) people. Pubmed, Web of Science, and Embase were queried to identify studies that examined an association between minority stress (including prejudice events and conditions, anticipation of rejection and discrimination, concealment or disclosure of SGM identity(ies), internalized stigma, or structural stigma) and a biological health outcome among SGM people. Included studies were coded for methodological approaches, study population, minority stress measure, biological outcomes, count of overall analyses, and count of analyses where an association was detected. Fifty-nine studies met inclusion criteria and included a total of 391 analyses between an element of minority stress and a biological outcome, among which 38% of analyses detected an association (44% detected this association when study outliers were removed). All elements of minority stress demonstrated associations with outcomes: multicomponent measures, prejudice events and conditions, and structural stigma demonstrated the highest proportion of associations. Associations with minority stress were detected for general physical health, sleep, immune, cardiovascular, metabolic, hormonal, brain health, allostatic load, epigenetic and transcriptional regulation. The highest proportion of associations were detected among sleep, immune, and hormonal outcomes. These studies evidence associations between minority stress and biological outcomes among gender minority people in addition to evidence among sexual minority people. Future research should consider increasing rigor in methodology and expanding our understanding of moderators and mediators of these relationships.

Introduction

The minority stress model puts forth the idea that minoritized groups have additional stress burden, over and above the burden of general stress, that systematically harms their health. This model, originally put forth by Brooks (1981) was further developed and tested by Ilan Meyer for sexual minority (SM) people across sexual orientations (Meyer, 1995, 2003). It has since been expanded to include gender minority stress and population-specific factors for gender minority (GM) individuals (Hendricks & Testa, 2012). Since its inception, it has been further developed to include additional mediating variables to explain the process by which stress leads to adverse mental health outcomes, for example through behavioral factors which impact health, sleep disturbance, and psychological distress (Christian et al., 2021) or through emotion dysregulation, social disruptions, and cognitive processes (Hatzenbuehler, 2009).

Minority stress has been debated, critiqued, and revised (e.g., Frost & Meyer, 2023), yet it continues to have relevance as it bears out across health studies and contexts with sexual and gender minority (SGM) people. New guiding models or elements have been proposed (e.g., social safety by Diamond & Alley, 2022). Further, the understanding of minority stress within an intersectional frame has been delineated (e.g., Parra & Hastings, 2018).

Through all of these adaptations, modifications, and debates, one thing is clear: SGM individuals continue to experience disparities across mental health and physical health metrics (e.g., Cicero et al., 2020; Tran et al., 2023). Complacency about this is not acceptable. Sadly, minority stress exposures are not lessening. Policy efforts have ramped up to target SGM, and in particular GM individuals, across the United States. Research studies have greatly unpacked the mechanisms and methods by which minority stress undermines mental health, but we have yet to make significant progress to change mental health outcomes for the better. Our understanding of how minority stress processes impact physical health is less developed. Specifically, we have yet to identify how disease processes develop at greater rates among SGM people, and what can be done to alleviate these processes. Understanding oppression among SGM individuals has the potential to help us understand the biological impacts of oppression more generally (Flentje, 2023).

In 2020, we published a systematic review of the literature up to 2019 on minority stress in relation to biological outcomes among SM people. In that review, we identified 26 studies that conducted 125 analyses testing the association between one or more elements of minority stress and at least one biological outcome. In that study, we found that all elements of minority stress had demonstrated an association with a biological outcome in at least one analysis. Among specific minority stressors, concealment of one’s identity was the most widely tested, with half of all analyses detecting a link. Internalization of stigma was tested the least and was found to be associated with a biological outcome in only 13% of analyses. The biological outcomes we observed in relation to minority stressors included general physical health, immune responses, HIV-specific outcomes, cardiovascular outcomes, metabolic outcomes, hormonal outcomes, and cancer occurrence and treatment side effects. Overall, 42% of analyses detected an association between an element of minority stress and a biological outcome, suggesting a strong but not entirely replicable signal. In the time since this review was published, there has been a growing interest in understanding how minority stress may impact the health of SGM people directly through biological processes. Further, the context for minority stress among SGM people has changed since 2020, particularly in relation to structural stigma. In 2020 and each year since, there has been a significant increase in legislative bills aimed at limiting GM individuals’ access to public accommodations, gender affirming healthcare, inclusion on sports teams, and policies related to education (U.S. Anti-Trans Legislation History, 2024). Although the potential impact of antitrans legislation is far-reaching, also significant within the last four years has been the increase in hate crime incidents, with now one in five hate crime reports being linked to anti-LGBTQ+ bias (Federal Bureau of Investigation, 2023; Human Rights Campaign, 2024).

The purpose of this review is to update the prior systematic review, focusing specifically on what has been done since our original review, and ensuring we expand our article search to include GM populations, who had been nearly entirely unstudied in the time of our prior review. Thus, the purpose of this review is to identify research published since 2019 that documented an analysis between an element of minority stress and a biological outcome among sexual and/or gender minority people. Our goal is to first identify if more recent research continues to support the hypothesis that minority stress impacts the biological cascade among SGM people. Further, we seek to identify if advances in the current research point to methods, minority stress elements, or outcomes that evidence these relationships to inform our understanding of these biological processes.

Methods

Data sources and search strategy

PubMed, Embase, and Web of Science were queried for publications between 2019 and 2024 for search terms identifying SGM populations, minority stress, and biological outcomes (Supplemental Material 1 Table S1). The initial search yielded 3,301 articles.

Inclusion criteria

To be included, studies had to meet the following criteria: (a) empirical in nature and published in peer-reviewed journals in English between 2019 and 2024; (b) include a measure of at least one minority stress process operationalized as prejudice events and conditions and enacted stigma, anticipation of rejection and discrimination, concealment or disclosure of sexual orientation and/or gender identity, internalized stigma, or structural stigma; (c) report biological outcomes measured through assays and tests or self-report; (d) provide a statistical test of the relationship between at least one minority stress process and at least one biological outcome; and (e) include a report of results for sexual and/or gender minority people. Minority stress or structural stigma exposures that contained other metrics (e.g., maternal health policies in a composite measure with SGM specific policies) were retained if most of the exposure was related to minority stress, but did not meet inclusion criteria if most of the measure was related to something else. Structural stigma was included if it was a commonly used direct metric (e.g., policies) but excluded for less clearly construct valid measures (e.g., progressiveness or percent of state voting for Republican candidates). HIV outcomes were excluded if they were related to lack of access to or persistence with medication (e.g., viral load among study participants who were differentially accessing and taking medications, seroconversion related to lack of PreExposure Prophylaxis), as this literature is voluminous and reflects a host of considerations outside of the scope of minority stress in relation to biological outcomes (e.g., medication access, availability, health care coverage, side effects, persistence). Minority stress exposures that were only attributed to a non-SGM related characteristic (e.g., weight, race) were included if they tested the minority stressor among SGM people. Minority stress was included when it reflected an extra stress burden for SGM people, thus affirmations were not included as the inverse of minority stress.

Review of the search results

The goal of this review was to conduct a rapid review (Smela et al., 2023), to identify the breadth of existing research within a limited time frame and update the previous review. Preliminary screening of titles and abstracts was conducted (1 author review), which led to the removal of 3,154 articles out of the initial 3,301 unduplicated search results. To determine if studies met inclusion criteria, the remaining 147 full text articles were reviewed by two team members in Covidence. When there was disagreement about whether a study met inclusion criteria, the third coauthor reviewed the article and provided input. This process yielded 59 final articles for data extraction (see Supplemental material 1 Figure S1 for the PRISMA Diagram).

Extraction and Coding of Studies

When studies included multiple analyses, the final models (typically fully adjusted for covariates) were counted and reported. In cases where final models did not include this analysis, preliminary (e.g., correlation analyses) were counted and reported; these were not double counted if they were in final models. Study characteristics (see Table S2 in Supplemental material 1) were extracted by one of two study reviewers. To assist with coding process cohesion, each reviewer conducted data extraction for their first five articles independently. The second reviewer verified each data entry within these extractions. After these first 10 extractions (five per reviewer), reviewers met to discuss and agreement on extraction was determined to be adequate. After that point, study characteristics were extracted by a single reviewer, and reviewed by a second reviewer to identify omissions to improve data quality. Any questions about extraction were discussed and decided together and a third reviewer resolved any conflicts. Study characteristics are reported for SGM samples, and if they were not reported separately by SGM status (e.g., race and ethnicity only reported for a larger sample that included non-SGM people), they were not recorded.

Studies were coded as measuring the following minority stress process(es): prejudice events (e.g., enacted stigma, discrimination, victimization, bullying, microaggressions); expectations of rejection and discrimination; internalized stigma (e.g., internalized homophobia or transphobia); concealment of identity; general or multicomponent minority stress (i.e., measuring multiple minority stress processes or overall minority stress); and structural stigma (i.e., stigma codified by policies, programs, and other sociological systems in which an individual lives). We coded studies as measuring gender minority stress, sexual minority stress, general minority stress (i.e., not attributed to specific identities), and stress attributed to the stigmatization of other identities or characteristics.

We accounted for both the study (included research studies) and analyses run within studies (i.e., multiple analyses within a single study). We examined how many analyses within each topic area detected an association between the minority stress component and the outcome, and report that here. When studies were identified as outliers in the number of analyses they ran (defined as a study that ran more than 20 analyses within the study on minority stress and a biological construct), we conducted a sensitivity analysis to consider the proportions both with and without the study. This was done in order to remove distortions that may occur from including a large number of analyses within a single study, and enabled us to identify if that outlier influenced overall observed proportions. There were two studies that met our criteria for outlier studies, which had 22 and 52 analyses within their studies.

Results

Overall results

In total, 147 studies were identified during abstract review, with 59 studies ultimately meeting inclusion criteria for this review (see Supplemental materials for CONSORT diagram). These studies and the summary of each of their results are provided in Table 1. Figure 1 provides an overarching summary of the results, including minority stress exposures, moderators and mediators incidentally identified, outcome types, and observed outcomes (including a count of the number of analyses in which these outcomes demonstrated an association with minority stress). Overall, the 59 studies ran 391 analyses, among these, 149 (38%) detected an association between a minority stress predictor and a biological outcome, or 44% of analyses (141 of 317) when the two studies that ran more than 20 analyses within the study were excluded. When all studies were considered with equal weight (each study provided its own proportion), 47% of analyses within studies detected an association (SD: 33%, Mdn: 50%, range 0–100% of analyses). Similarly, when the two studies that ran more than 20 analyses within the study were excluded, 48% of analyses within studies detected an association (SD: 34%, Mdn 50%, range 0–100% of analyses). Proportions of analyses demonstrating an association by study methodology, minority stressor, and biological outcome type are in Figure 2. In most (93%) of the studies, the test of minority stress in relation to the biological outcome was a primary analysis.

Table 1.

Included studies, their main results, their method, the number of SGM people within the study, and the biological outcome studied

Citation	Summary of Main Results	Method	SGM (n)	Biological outcome(s)
Adebajo, et al., 2023	Sexual stigma was associated with greater odds of cardiovascular and metabolic risk factors among SGM living with HIV in all analyses: both comparing medium stigma and high stigma to low, and looking at 1–2 and 3–5 cardiovascular and metabolic risk factors versus none.	Observational longitudinal	761	Cardiovascular outcomes; Metabolic outcomes
Ancheta, et al., 2023	Among students in grade 9–12 in the United States, there was no interaction between sexual minority identities and victimization, nor sexual minority identities and policies that protect LGBT students in odds of obesity.	Observational crossectional	9,341	Metabolic outcomes
Baiocco, et al., 2024	Among LGB older adults in Italy over 65 years of age, physical health was better among people with fewer stressors related to heterosexism (e.g., vigilance, isolation, discrimination and prejudice events, and victimization) and among people who were more out to the people in their life.	Observational crossectional	82	General physical health
Belloir, et al., 2022	Among gender minority participants, everyday discrimination experiences were related to past 7-day sleep disturbance.	Observational crossectional	194	Sleep
Belloir, et al., 2024	This 30-day longitudinal daily diary and fit-bit tracking study of SGM people study found that daily discrimination was not associated with same night total sleep time or sleep related impairment, but was associated with same-night sleep disturbance. Daily anticipated discrimination was not associated with same night sleep disturbance or total sleep time, but was associated with sleep related impairment on the following day. Lifetime daily discrimination was associated with total sleep time, but not with same night sleep disturbance or next day sleep related impairment.	Observational longitudinal	43	Sleep
Boehmer, et al., 2022	More lifetime discrimination experiences were associated with poorer health-related quality of life and physical health among 127 sexual minority survivors of colorectal cancer. Outness was not significantly associated physical quality of life or health.	Observational crossectional	127	General physical health; Other: Health-related quality of life
Caceres et al., 2022	Among gender minority individuals, those who experienced high stigma consciousness and less gender-related discrimination and those with high stigma consciousness and gender-related discrimination reported more sleep disturbance than those with low stigma consciousness and low gender-related discrimination. In addition, gender minority individuals with high stigma consciousness and gender-related discrimination had shorter sleep than those with reporting lower levels of these minority stressors, but individuals with high stigma consciousness and low gender related discrimination did not have shorter sleep duration than those with low levels of both.	Observational longitudinal	279	Sleep
Caceres BA et al., 2023	Among sexual minority adults assigned female at birth, people with greater internalized homophobia were more likely to develop hypertension over 7 years. Discrimination and stigma consciousness did not predict incidence of hypertension.	Observational longitudinal	380	Cardiovascular outcomes
Campbell, et al., 2024	A correlation analysis suggested no significant relationship between LGBTQ-related discrimination experiences and sleep quality.	Observational crossectional	74	Sleep
Chan & Fung, 2021	Greater sexual orientation-related primal threat and experienced discrimination were associated with greater sleep disturbance among LGB adults in Hong Kong. Anticipated discrimination and sexual orientation-related primal threat were associated with worse physical health. Anticipated and experienced discrimination were related to sleep disturbance and physical health via sexual orientation-related primal threat.	Observational crossectional	401	General physical health; Sleep
Choo, et al., 2022	Experiences of LGB discrimination, other types of discrimination, or both types of discrimination were examined in relation to sleep quality, unrestful sleep, and long sleep latency among LGB adults. LGB discrimination was only related to unrestful sleep, while other types of discrimination and both types of discrimination were related to all sleep outcomes.	Observational crossectional	2,192	Sleep
Cook, et al., 2022	Among young sexual minority men those with more discrimination experiences had greater risk of having high risk C-reactive protein (CRP) than those with low discrimination exposure, but there was no relationship between discrimination and average risk CRP, nor was there a relationship between LGBQ-specific microaggressions and average or high risk CRP.	Observational crossectional	60	Immune response
Cook, et al., 2024	This pilot study among young sexual minority men ran demonstrative analyses and found a relationship between discrimination experiences and salivary cortisol levels, but detected no relationship between discrimination and high-sensitivity CRP or average minutes of sleep.	Observational longitudinal; Pilot study	19	Sleep; Cardiovascular outcomes; Hormonal outcomes
Devlin, et al., 2024	Microaggressions related to sexual minority status were related to greater odds of obesity and victimization related to LGBT status were related to reduced odds of obesity compared to reference weight (BMI 18.5- <25), but sexual minority internalized stigma was not related to obesity. Neither microaggressions related to sexual minority status, victimization related to LGBT status, nor internalized stigma related to sexual minority status results in greater odds of being overweight compared to the reference weight (BMI 18.5- <25).	Observational crossectional	367	Metabolic outcomes
Dibble, et al., 2023	This study did an item level analysis of discrimination experiences (10 types) and anticipated discrimination (3 types) among sexual minority men, and tested the relationship between each type of discrimination experience and AM cortisol, PM cortisol, average cortisol, and daily cortisol change among cisgender sexual minority men. Of these analyses only healthcare providers gossiping about the individual was related to PM cortisol and average cortisol, and police refusing to protect the individual was related to AM cortisol and average cortisol.	Observational crossectional	667	Hormonal outcomes
DuBois & Juster, 2022	An index of multicomponent gender minority stressors was not significantly associated with allostatic load.	Observational longitudinal	65	Allostatic load
DuBois, et al., 2024	Among gender minority adults (19 years or older) in the United States, enacted stigma specific gender minority status was negatively associated with 1cortisol awakening response and cortisol daily decline as measured by salivary cortisol. There were no significant differences in cortisol across high, medium, and low enacted stigma exposure groups when participants woke up, but there was significantly lower cortisol among participants with experiences of high levels of stigma at 30 minutes after waking compared to those who experienced low stigma. At bedtime, those who experienced high levels of stigma had higher cortisol before sleeping than those who experienced low and medium levels of stigma. Internalized stigma specific to gender minority status was negatively associated with cortisol awakening response, but not significantly associated with cortisol daily decline.	Observational longitudinal	124	Hormonal outcomes
Eisner, et al., 2024	Among both LGBTIQ+ and cisgender heterosexual (largely LGBTIQ+ allies) Swiss people, cortisol concentrations measured in hair increased before a vote, and decreased after the vote for marriage equality in Switzerland (which granted marriage for LGBTIQ+ people and included joint adoption, facilitated citizenship naturalization, and allowing for insemination for family-building), and there was no difference in this effect by LGBTIQ+ status. Exposure to campaigns against marriage equality increased cortisol and cortisone concentrations among LGBTIQ+ people from baseline to shortly before the election, but the campaign was not related to changes in cortisol or cortisone from shortly before the vote to after the vote.	Observational longitudinal	218	Hormonal outcomes
Eom, et al., 2022	Among transgender and non-binary adults in South Korea, experiences of transgender identity discrimination in the past 12 months was associated with sleep problems (defined by short sleep, poor sleep quality, and/or the use of alcohol or medication to sleep). Among those with families not supportive of or not aware of their transgender/non-binary identity, past 12-month experiences of transgender identity discrimination was associated with sleep problems. Past 12-month discrimination was not associated with sleep problems among those with supportive families.	Observational crossectional	583	Sleep
Everett & Agénor, 2023	There was a 3 way interaction between race, sexual orientation, and non-discrimination policies in relation to maternal hypertension, suggesting lower risk of maternal hypertension among Black lesbian and bisexual women living in states with sexual orientation-related nondiscrimination laws (but not heterosexual women), among White women, more nondiscrimination laws were associated with less maternal hypertension for both lesbian and bisexual women and heterosexual women.	Observational longitudinal	87	Cardiovascular outcomes
Fahey, et al., 2024	This pilot study found no relationship between an induced minority stress exposure and changes in salivary cortisol.	Experimental; Pilot study	8	Hormonal outcomes
Figueroa WS et al., 2021	Experiences of minority stress including discrimination and anticipation of discrimination were related to greater salivary cortisol upon awakening and at 45 minutes after, but not in the two evening measures, and there was no interaction with within or between person variation in minority stress experiences and temporal cortisol slopes.	Observational longitudinal	49	Hormonal outcomes
Fredriksen-Goldsen, et al., 2023	Among sexual and gender minority people in the US age 50 years or older, lifetime experiences of violence (some LGBT specific, some not) were associated with having more chronic health conditions and self-reported overall health. Past year microaggressions and lifetime discrimination experiences were not associated with having more chronic health conditions and overall health.	Observational crossectional	2,450	General physical health
Fredriksen-Goldsen, et al., 2023	Among older LGBTQ caregivers, daily discrimination was related to physical health over time, but microaggressions, lifetime discrimination, and internalized stigma related to being LGBTQ were not related to physical health over time.	Observational longitudinal	754	General physical health
Friedman, et al., 2022	In a longitudinal study among sexual minority men across several cities in the US, participants who reported enacted intersectional stigma (defined by experiences of discrimination targeting 2 or more identities) had greater odds of having hypertension, diabetes, and dyslipidemia.	Observational longitudinal	1,806	Cardiovascular outcomes; Metabolic outcomes
Ghanooni et al., 2022	Among sexual minority men living with HIV who had undetectable HIV viral load and recent stimulant use, general sexual minority stress was associated with faster extrinsic epigenetic acceleration aging, decreased DNA-methylation derived estimates of telomere length, and fewer naive CD4+ and CD8+ cells. More internalized stigma was associated with fewer naive CD4+ and CD8+ cells. More outness was associated with more CD4+ and CD8+ cells, and decreased IL-6. Analyses were controlled for negative affect and recent stimulant use. The same pattern was observed while controlling for ASI Drug Score instead of recent stimulant use.	Observational crossectional	52	Immune response; Aging (cellular)
Gibbs, 2023	Sexual orientation related microaggressions were related to sleep disturbance among sexual minority men, and this relationship was only partially mediated by substance use (i.e., remained when substance use was taken into account).	Observational crossectional	239	Sleep
Gibbs & Fusco, 2023	Final study models suggested no direct relationship between SM related internalized stigma, discrimination and harassment experiences, nor microaggressions and sleep disturbance, as relationships between these variables were mediated by anxiety and perceptions of stress.	Observational crossectional	239	Sleep
Gillespie, et al., 2024	Among racial minoritized sexual minority men living with HIV, daily racial discrimination experiences were related to computer assisted self-interview assessed hypertension measured in the clinic, mean systolic and diastolic blood pressure measured in the clinic, and normal blood pressure in clinic but not hypertension identified identified by ambulatory 24-hour blood pressure. Sexual orientation discrimination was not related to any of these outcomes. Neither sexual orientation discrimination or racial discrimination were related to hypertension in 24-hour ambulatory blood pressure monitor readings, systolic or diastolic blood pressure in 24-hour blood pressure readings, a nocturnal dip in systolic or diastolic blood pressure, or in clinic hypertension with no hypertension detected through 24-hour ambulatory blood pressure.	Observational longitudinal	60	Cardiovascular outcomes
Huang, et al., 2022	Among gay men living in Taiwan, sexual minority stress alone was not associated with obesity. There was a significant interaction between sexual minority stress and sexual abuse, such that sexual minority stress predicted obesity among gay men who had experienced childhood sexual abuse.	Observational longitudinal	731	Metabolic outcomes
Huebner, et al., 2021	A laboratory social evaluative task with a minority stress condition (antigay confederate) elicited increased systolic blood pressure, heart rate, and salivary cortisol, and reduced high frequency heart rate variability when compared to a pro-gay confederate condition. For all outcomes these changes were evidenced from baseline to task performance within the minority stress condition. Changes in systolic blood pressure, heart rate, and high frequency heart rate variability maintained during the recovery period for the minority stress condition, but cortisol returned to baseline levels during the recovery period. There was no difference in diastolic blood pressure between the minority stress and pro-gay condition, nor were there differences in high frequency heart rate variability during the waiting and thinking period of the experiment (before task performance).	Experimental	134	Cardiovascular outcomes; Hormonal outcomes
Juster, et al., 2019	Whether or not sexual minority participants had disclosed their sexual orientation to themselves, friends, and family was tested as a predictor of response to a modified, non-minority stress specific, social stress task. Disclosure status was not related to heart rate, mean arterial pressure, systolic blood pressure, nor diastolic blood pressure among sexual minority participants in response to the stress task.	Experimental	46	Cardiovascular outcomes
Juster, et al., 2024	Structural stigma was related to allostatic load among sexual minority men, but not sexual minority women.	Observational crossectional	864	Allostatic load
Keenan, et al., 2021	Compared to Black and White heterosexual women, LGB Black and White women had stronger cortisol reactivity and heart rate variability reactivity (pre-20 min post and pre to task, respectively) in response to a minority stress adapted Trier Social Stress Task. There were no differences in cortisol or heart rate variability recovery (20–40 minutes post and task to 10 minutes post, respectively).	Experimental	150	Cardiovascular outcomes; Hormonal outcomes
Kim, et al., 2023	Lifetime discrimination and victimization experiences and internalized stigma (both related to LGBT identity) were related to physical health related quality of life over time, but not physical functioning among sexual and gender minority older adults with cognitive impairment.	Observational longitudinal	855	General physical health
Kolp, et al., 2020	General minority stress (defined by non-affirmation of gender identity) was not related to trauma-related sleep disturbance, but internalized transphobia was related to trauma-related sleep disturbances.	Observational crossectional	191	Sleep
Lambrou et al., 2022	Among transgender and gender expansive adults in the US age 50 years or older, experiences of discrimination in medical settings was associated with reporting “poor to fair memory” and worsening memory. Experiencing violence related to gender identity was not associated with experiencing poor to fair memory (in final adjusted models) or worsening memory (in bivariate analyses).	Observational crossectional	669	Cognitive health
Layland, et al., 2022	Among sexual minority Black and Hispanic/Latino men, those experienced racism had lower odds of reporting better self-rated health than those who experienced minimal or no stigma. Those who experienced compound stigma (racism and homonegativity) had greater odds of reporting sleep disorders. The stigma classes of select social stigma, homonegatvitiy, multiform racism, and compound stigma compared to minimal stigma did not significantly relate to odds of asthma, sleep disorders, gastrointestinal disorders, and self-rated health in any of the other analyses.	Observational longitudinal	435	General physical health; Metabolic outcomes; Other: Asthma
Lessard, et al., 2020	Among LGBTQ+ teens (13–17 years old), bullying based on weight, gender, race/ethnicity, religion, disability, gender typicality, and sexuality were positively correlated with difficulty falling asleep.	Observational crossectional	17,112	Sleep
Li et al., 2020	Among Black and Latino men who have sex with men living without HIV, homophobic violence was associated with greater CTRA gene expression.	Observational longitudinal	70	Epigenetic and transcriptional regulation outcomes
Li et al., 2022	Experiences of anti-gay victimization were not related to upregulated inflammatory gene expression among Black and Latinx sexual minority men living with HIV.	Observational longitudinal	147	Epigenetic and transcriptional regulation outcomes
McQuillan et al., 2021	The composite gender minority stress and resilience scale score was associated with elevated CRP among 50 transgender American youth (age 9–20), but individually the subscales of nondisclosure, non-affirmation, negative expectations of one’s future due to being transgender, and internalized transphobia were not associated with differences in CRP.	Observational crossectional; Pilot study	50	Immune response
Mereish & Goldstein, 2020	Among SGM people, past year experiences of discrimination were not associated with diabetes mellitus, hypertension, excess body fat, high cholesterol, or the multicomponent cardiovascular disease risk index. Those reporting greater internalized sexual minority stigma had greater odds of reporting diabetes mellitus, but there was no significant effects of internalized stigma on hypertension, excess body fat, high cholesterol, or the multicomponent cardiovascular disease risk index.	Observational crossectional	670	Cardiovascular outcomes; Metabolic outcomes
Mijas, et al., 2021	Among Polish cisgender gay men, greater enacted stigma defined by family rejection predicted greater cortisol reaction to the first day Trier Social Stress Test (TSST) cortisol response. Greater general minority stress defined as vicarious trauma (e.g., hearing about hate crimes against LGBT people) predicted lower cortisol response. Isolation due to LGBT identity, concealment of sexual minority identity, victimization and harassment due to LGBT identity did not predict cortisol response to TSST.	Observational longitudinal	49	Hormonal outcomes
Oh et al., 2024	Among cisgender adults in the US, sexual minority status was related to increased daytime sleepiness among sexual minority women via everyday discrimination experiences, but not sexual minority men.	Observational crossectional	315	Sleep
Parra & Hastings, 2020	Among Latinx sexual minority people, challenges to identity integration (multicomponent minority stress related to integrating one’s sexual and cultural identity) was related to lower cortisol intercepts, but heterosexist and racial discrimination were not associated with intercepts (baseline at waking), and none of these were related to cortisol slopes (degree of change over 2 consecutive days, 3 measures per day). Racial and heterosexist discrimination were individually related to cortisol intercepts (but not slopes) via challenges to identity integration.	Observational longitudinal	51	Hormonal outcomes
Parsons, 2020	Higher levels of day-to-day mistreatment were associated with poor sleep (difficulty falling asleep and staying asleep) but not with blood pressure or high sensitivity CRP among plurisexual adults.	Observational crossectional	133	Sleep; Immune response; Cardiovascular outcomes
Poteat, et al., 2021	Among transgender and gender expansive people, everyday experiences of discrimination were not associated with having ever been diagnosed with any cardiovascular condition (heart condition or heart disease, angina, heart attack, hypertension, or stroke) or venous thromboembolism.	Observational crossectional	114	Cardiovascular outcomes
Rosati, et al., 2021	LGB and heterosexual people were exposed to laboratory-based cognitive arithmetic, general stress, and (only for LGB people) sexual orientation specific tasks to study cardiovascular and hemodynamic responses. Among these participants, there was no significant difference in hemodynamic profile (HP) reactivity and compensation deficit (CD) between heterosexual and LGB people. Among the LGB participants, there was no difference in HP and CD when comparing the general stress and sexual minority stress tasks. However, there was more vascular hemodynamic response in reactivity to the sexual minority stress task compared to the general stress task. Self-reported everyday minority stress experiences was negatively associated with HP and CD reactivity in the minority stress task. Vagal regulation of heart rate (measured by root mean square of successive difference) at rest (pre-task) was not associated with compensating during the minority stress task.	Observational longitudinal	19	Cardiovascular outcomes
Ross, et al., 2023	Among a cohort of sexual minority men and a gender minority person assigned male at birth in the US or Canada who had been treated for prostate cancer, everyday discrimination was associated with prostate cancer treatment outcomes including urinary function, urinary bother, bowel function, hormonal function, and hormonal bother. Everyday discrimination was not associated with overall physical health-related quality of life or with sexual function or sexual bother.	Observational crossectional	193	General physical health; Other: Prostate cancer-specific quality of life
Sattler, et al., 2021	There was no difference in cortisol or testosterone response to a general social stress (TSST) versus sexual minority stress modified stress task (TSST modification) among gay men.	Experimental	33	Hormonal outcomes
Segovia & Sparks, 2024	Among LGB adults in the US, those who experienced greater internalized homophobia or were out to all of most of their family had greater odds of a sleep disorder diagnosis, while being out to all or most of one’s straight friends was related to less odds of a sleep disorder diagnosis. There was no difference in odds of being diagnosed with a sleep disorder based on everyday discrimination, felt stigma, and outness to coworkers or health providers.	Observational crossectional	701	Sleep
Tepman & Wong, 2024	Among sexual minority adolescents in the UK, experiences of bullying or victimization from other children at age 11 was related to nocturnal awakening at age 14. Experiences of bullying or victimization from other children at age 11 did not predict sleep latency at age 14.	Observational longitudinal	1,922	Sleep
Veale, 2023	Among transgender people from New Zealand, enacted stigma was positively associated with hypertension, hypercholesterolemia, and general poor/fair health. Enacted stigma was not associated with myocardial infarction, stroke, or diabetes.	Observational crossectional	891	General physical health; Cardiovascular outcomes
Vincent et al., 2021	Among sexual minority men living with HIV who use methamphetamine, greater outness predicted lower kynurenine/tryptophan (K/T) ratio over time. General sexual minority stress measured by the CARS scale did not predict K/T ratio. There was a significant interaction between race/ethnicity and outness on K/T ratio ‚ increased outness was associated with lower K/T ratio among White men but not Men of Color.	Observational longitudinal	97	Immune response
Wardecker, et al., 2021	Among 81 sexual minority men and women and 1,956 heterosexual people, daily discrimination and lifetime discrimination both mediated the relationship between sexual orientation and IL-6 and CRP.	Observational longitudinal	81	Immune response
Wolfe et al., 2024	Among US veterans age 45 years or older who identify as transgender or gender expansive, experiences of internalized transphobia and enacted gender minority stigma (i.e., non-affirmation) were associated with greater prevalence of subjective cognitive decline.	Observational crossectional	3,155	Cognitive health
Wood & Cook, 2019	Among sexual minority people 24–33 years old in the United States, perceived discrimination was related to high sensitivity CRP (hsCRP) but only in the presence of an interaction with father support (how close you are to your father). Father support moderated the relationship between perceived discrimination and hsCRP, such that those who experienced discrimination had higher hsCRP than those who did not among participants with less support from their father. The interaction between support from one’s mother and discrimination was not significant.	Observational crossectional	445	Immune response; Cardiovascular outcomes
Xavier Hall et al., 2024	Among middle age (i.e., 39 years or older) sexual minority men living with HIV, discrimination experiences and internalized homophobia were not associated with dementia risk scores at baseline or 6-month follow-up.	Observational longitudinal	196	Cognitive health

Figure 1.

Observed outcomes, moderators, and mediators among studies (n=59) testing minority stress and biological outcomes

Note: The counts of analyses that detected associations are the author’s best estimate, as the full count of analyses were not consistently clearly reported.

Figure 2.

Proportion of detected analyses by biological outcome, minority stress type, and study design

Sample Characteristics

Overall, studies contained between 8 and 17,112 SGM people (M = 885, Mdn = 194, SD =2523). Studies used very different metrics to report sex, gender, sexual orientation, and transgender status as well as other demographic information. This meant that these characteristics were not uniformly available for all studies, and thus considered less reliable and may not exactly capture the actual demographics of people in the studies. By sexual orientation, 61% of studies contained monosexual SGM people, 51% of studies contained plurisexual SGM people, and 8% contained asexual SGM people. Considering GM status, 42% of studies contained one or more GM people (range 1–5,637) and 17% contained only GM people among the SGM sample in the study. Among studies, 25% contained cisgender SM men, and an additional 31% of studies contained SM men (cisgender status not specified), 17% contained cisgender SM women, and an additional 19% contained SM women (cisgender status not specified), 25% contained gender expansive people, 20% contained transgender men, and 15% contained transgender women.

No studies contained exclusively gender expansive people, exclusively transgender men, or exclusively transgender women; two studies included exclusively people they defined as transmasculine, but this included both transgender men and gender expansive people. Among the ten studies that only included GM people across the gender spectrum (who were not included in the prior systematic review), 25 of 46 analyses (54%) detected an association between a minority stress predictor and a biological outcome. Fourteen percent of studies contained SGM people living with HIV and 10% of studies had study samples where all SGM people in the study were living with HIV. Among studies where all SGM people in the study were living with HIV, 17 of 52 analyses (33%) detected a relationship.

Among studies that reported race and ethnicity among SGM people specifically, a mean of 5% of partcipants were Asian (17 studies reported, SD = 4%, range 0%−18%, Mdn = 4%), 19% of participants were Black (33 studies reported, SD: 15%, range 2%−60%, Mdn = 16%), 23% of participants were Latina/Latino/Latine/Latinx or Hispanic (30 studies reported, SD: 25%, range 0.4%−100%, Mdn = 12%), 0.5% of participants were Middle Eastern or North African (1 study reported), 5% of participants were Native American or Indigenous (6 studies reported, SD: 5%, range 1%−13%, Mdn: 3%), 6% were Native Hawaiian or Pacific Islander (4 studies reported, SD:10%, range 0.1%−22%), 63% of participants were White (36 studies reported, SD: 23%, range 1%−100%, Mdn = 69%), 11% were multiracial (10 studies reported, SD: 14%, range 2%−47%, Mdn: 7%), and 11% were reported as another race or ethnicity (i.e., individuals who studies reported within an “Other,” “Another race or ethnicity,” or similar combined category; 17 studies reported, SD: 10%, range 1%−32%, Mdn: 9%).

Results by study methodology

Studies that incorporated clinic-based (i.e., based in healthcare settings) data collection (n = 4) included 33 total analyses, among which 10 (30%) detected associations between minority stress and a biological outcome. Studies that included Internet data collection (n = 23) conducted 155 total analyses, among which 59 (38%) detected an association. Studies that incorporated in-person data collection (n = 28) conducted 174 total analyses, among which 70 (40%) detected an association. Among the studies that used another form of data collection (n = 11, involving home biospecimen sample collection or mailed paper surveys), 31 of 115 analyses (27%) detected an association.

Studies that used cross-sectional methods ran 207 total analyses: among these, 71 (34%) detected an association between the minority stressor and the outcome. Among studies using longitudinal observational methods, 59 of 145 (41%) total analyses run within these studies detected an association. Studies using experimental methods detected associations in 19 of 39 total analyses (49%), 19 of 38 analyses (50%) if excluding the experimental study that was also a pilot study. Studies that were identified as pilot studies detected associations in 2 of 9 analyses run (22%).

Results by minority stress processes

Minority stress processes were primarily measured through self-report (50 studies, 85%) but also used observational data (4 studies, 7%, e.g., structural stigma measured through policies) and investigator orchestrated exposures (5 studies, 8%). Prejudice events and conditions were the most frequently measured minority stressor (41 studies, 69%), a general or multicomponent measure was also frequently used (20 studies, 34%). Expectations of rejection and discrimination (4 studies, 7%), internalized stigma (13 studies, 22%), concealment of identity (8 studies, 14%), and structural stigma (4 studies, 7%) were also measured. Twenty-three studies (39%) measured more than one component of minority stress within the study. Sixteen studies (27%) measured gender minority stress, thirty-nine (66%) measured sexual minority stress, nineteen (32%) reported non-specific minority stress, and 10 (17%) reported minority stress related to another personal characteristic observed among SGM people.

Prejudice events and conditions

Of the 51 studies testing an analysis between a prejudice event or condition and a biological outcome, 79 of 214 total analyses (37%) detected an association. The studies ran between 1 and 40 analyses (M: 5.2, SD: 6.8 Mdn: 4, range 1–40). Given that two of these studies ran over 20 analyses (Dibble et al., 2023; Gillespie et al., 2024), excluding these studies meant that among 49 studies, 71 of 152 analyses (47%) detected the association. The majority of studies examined discrimination; less commonly examined constructs include school victimization or bullying, violence and victimization, microaggressions, or multicomponent measures of enacted stigma (e.g., measuring discrimination, harassment, and rejection) among SGM people.

Expectations of rejection and discrimination

Within the four studies testing an analysis between expectations of rejection and discrimination and a biological outcome, 2 of 18 total analyses (11%) detected an association. All four studies used self-report methods to consider anticipated stigma, with three examining different subconstructs (i.e., stigma consciousnesses, anticipated healthcare stigma, and negative expectations of the future).

Concealment of identity

Within the eight studies that investigated concealment of identity in relation to a biological outcome, 25 analyses were conducted, among which 7 (28%) detected an association. These studies used the Outness Inventory (Mohr & Fassinger, 2000), tallied the percent or number of people participants were out to, used the vigilance subscale of the Daily Heterosexist Experiences Questionnaire (DHEQ, Balsam et al., 2012), and used the nondisclosure subscale of the Gender Minority Stress and Resilience Scale (GMSRS, Testa et al., 2015).

Internalized stigma

Within the 13 studies that investigated internalized stigma in relation to a biological outcome, 27 analyses were conducted, among which 9 (33%) detected an association. Frequently used measures of internalized stigma included the GMSRS internalized transphobia subscale (3 studies) and the full or revised versions of the Internalized Stigma Scale (Herek, 1988; Herek et al., 2009, 5 studies).

General stress related to SGM status or multicomponent measure of minority stress

Within the 20 studies that tested a multicomponent measure of minority stress in relation to a biological outcome, 46 of the 95 analyses (48%) detected an association. Self-report measures of general minority stress or multicomponent included the GMSRS (3 studies), the Cultural Assessment of Suicide (Chu et al., 2013, 2 studies), and the DHEQ (Balsam et al., 2012, 3 studies). Some of these studies clustered or summed multiple measures of minority stress (e.g., stigma consciousness and everyday discrimination as in Caceres 2022). Many of the investigator-initiated minority stress exposures were testing general or multicomponent minority stress. Several tested modifications of the Trier Social Stress Test (TSST, Kirschbaum et al., 1993), with modifications such as reflections on past experiences of discrimination or rejection (e.g., following Hatzenbuehler & McLaughlin, 2014).

Structural stigma

Within the 4 studies that examined structural stigma, 6 of 13 total analyses (46%) detected an effect. These studies investigated structural stigma as operationalized by marriage equality, nondiscrimination laws, hate crime laws, and SGM-protective school policies (e.g., bullying prevention). Of these studies, 3 examined policies based in the United States and 1 was based in Switzerland.

Results by biological outcome or process

Methodology

Twenty-eight studies (47%) used an objectively measured biological outcome, while 33 (56%) used a self-reported outcome. Among studies using self-reported outcomes, 69 of 178 analyses (39%) detected an association. Among studies using objectively measured outcomes, 85 of 226 (38%) detected an association. Forty-five studies (76%) tested only one general category of outcome (e.g., immune) within the study.

General physical health

Nine studies examined general physical health outcomes running 32 analyses, among which 12 (38%) detected a relationship between minority stress and physical health. General physical health outcomes tested in relation to minority stress included self-reported health; changes in physical functioning or activities; health related quality of life, and self-rated physical health.

Sleep

Seventeen studies examined sleep-related outcomes; 59% of analyses (36 out of 61) showed a relationship between minority stress and sleep. Studies examined sleep disturbances or nocturnal awakening, sleep disorder diagnosis, difficulty getting to sleep, sleep quality, sleep-related impairment, sleep duration, daytime sleepiness, and overall sleep problems (common measures included PROMIS and PSQI).

Immune outcomes

Seven studies examined minority stress and immune outcomes, 52% of analyses (15 out of 29) evidenced an association. Studies examined C-reactive protein (CRP) and high sensitivity CRP, kyneurinine tryptophan ratio, CD4+ and CD8+ T-cell counts, CD14 and CD163, IL-6, and TNF-alpha.

Cardiovascular outcomes

Thirteen studies examined a cardiovascular outcome including blood pressure (DBP, SBP, 24 hour ambulatory BP and nocturnal dip), hypertension, heart rate and heart rate variability, inter-beat intervals, mean arterial pressure, cardiac output, cardiometabolic disease and risk factors, and cardiovascular disease (heart attack, stroke, heart failure). Among these studies, 41% of analyses (32 of 78) detected an association. When the study that ran over 20 analyses (Gillespie et al., 2024) was excluded, 28 of 56 analyses (50%) detected an association.

Metabolic outcomes

Seven studies examined a metabolic outcome, among these only 16% of analyses (6 of 37) showed an association between minority stress and metabolic outcomes. These studies examined cholesterol, BMI, high-density lipoprotein, diabetes, dyslipidemia, excess body fat, overweight or obesity, and gastrointestinal disorders.

Hormonal outcomes

Eleven studies examined a hormonal outcome; 28% of analyses (31 of 109) detected an association. When the study that ran over 20 analyses was excluded (52 total analyses, Dibble, et al., 2023), we found that 27 of 59 analyses detected an association(46%). All of these studies examined cortisol, from either hair or saliva as an outcome, except one that examined testosterone.

Brain health outcomes

Three studies examined an outcome related to brain health, focused on memory, cognitive decline, or dementia. An association between minority stress and a brain health outcome was detected in 29% of analyses (4 of 14). All of these outcomes were measured via self-report: the CADIE score for dementia based on mid-life risk factors (Xavier Hall et al., 2024) self-rated memory quality (Lambrou 2022), and the BRFSS subjective cognitive decline module (Wolfe 2024).

Allostatic load

Two studies examined allostatic load, and one out of three analyses (33%) detected an association. These studies examined allostatic load by calculating the number of dysregulated biomarkers (e.g., blood pressure, CRP, cortisol, cholesterol, glycosylated hemoglobin).

Epigenetic and transcriptional regulation outcomes

Three studies examined epigenetic or transcriptional regulation outcomes, among these studies, three of eight analyses (38%) detected a relationship. One study examined cellular aging measured through DNA methylation (DNA methylation based estimates of leukocyte telomere length and accelerated epigenetic aging), while two other studies examined gene expression quantified through the Conserved Transcriptional Response to Adversity (CTRA).

Other outcomes

Studies also examined self-reported cancer-related quality of life (Ross 2023, six out of eight analyses showed a significant relationship with enacted stigma), asthma (Layland 2022, none of the four analyses evidenced an association), and health-related quality of life (Boehmer 2022, three out of seven analyses evidenced an association).

Discussion

This review clearly documents the exponential increase in research investigating biological processes in relation to minority stress in recent years, with 59 studies meeting inclusion criteria published since 2019, compared to only 26 that met inclusion criteria in our prior review which included all studies published before 2019 (Flentje et al., 2020). Similar to our prior review, we found that all elements of minority stress including prejudice events and conditions, anticipated stigma, concealment of minority status, internalized stigma, structural stigma, and multicomponent metrics of minority stress demonstrated an association with biological outcomes. Studies detected associations between elements of minority stress and overall physical health (general physical health, more chronic health conditions, health related quality of life), sleep outcomes (sleep disturbance, sleep disorders, unrestful sleep, nocturnal awakening, sleep impairment, total sleep time, sleep problems, daytime sleepiness), immune outcomes (CD4+ and CD8+ cells, IL-6, kynurenine-tryptophan ratio, C-reactive protein), cardiovascular outcomes (hypertension, hypercholesterolemia, blood pressure, heart rate variability, vascular hemodynamic response and profile, cardiovascular risk factors), metabolic outcomes (diabetes, dyslipidemia, obesity), cortisol (cortisol intercepts, PM cortisol and before sleeping, AM cortisol and at and after awakening, average cortisol, cortisol daily decline, cortisol and cortisone concentrations), brain health (poor or worsening memory), allostatic load, epigenetic and transcriptional regulation-related outcomes (conserved transcriptional response to adversity related gene expression, accelerated epigenetic aging, DNA-methylation estimated telomere length), and other outcomes (health related quality of life and prostate cancer treatment outcomes including urinary function, urinary bother, bowel function, hormonal function, and hormonal bother). In many respects, the results of this review are similar to our prior systematic review, with evidence for an association across biological systems between minority stress exposure and biological outcomes. In the present study, we found that the volume of evidence has increased and many new biological outcomes have been investigated, or investigated with more studies or at greater depth.

In the prior review period (Flentje et al., 2020), studies focused nearly exclusively on SM and not GM people. GM people were not the focus of the prior review due to a lack of research studies on minority stress and biological outcomes among this population in the prior review period. In this study, we found that 42% of studies contained GM people, and 17% of studies were exclusively conducted with GM people. The studies that were exclusively among GM people detected associations between minority stress and biological outcomes, suggesting that minority stress is related to biological outcomes among both SM and GM people.

At an analysis level, this review was very similar in the proportion of analyses that detected effects between minority stress and a biological outcome among SGM people. Overall, this study found that 38% of analyses detected an association between an element of minority stress and a biological outcome—this number jumped to 44% when the two outlier studies that ran over 20 analyses per study were excluded. In our prior review, 42% of analyses had detected an association. This suggests the present review replicates the inconsistent associations between minority stress and biological outcomes that was found in the prior review period. The level of scientific rigor used within a study appears to be related to whether or not a study detects a statistical association. For example, as would be expected, pilot studies detected associations less frequently (approximately one in five analyses) than other studies, likely due to small, underpowered samples given their pilot nature. In contrast, experimental studies detected associations in around half of analyses, which was much higher than observational crossectional studies (only about one-third of analyses). Observational longitudinal studies were slightly better, with around two out of every five analyses detecting an association.

In contrast to what we expected, method of measurement of the biological outcome or process did not appear to alter detection of an association. Studies that used self-report and objectively measured outcomes produced nearly the same rates of detection of association (39% and 38%, respectively), suggesting that patient-reported outcomes may be a valid way of capturing some underlying biological impacts of minority stress. Alternatively, as a research area still in its infancy, we have not yet identified which biological outcomes are the most impacted by minority stress, which could mean we still have many null results to contend with in analyses while we identify the strongest and most replicable biological signals.

When examining results by different types of minority stressors, the highest proportion of associations (nearly one half) was observed between minority stress and a biological outcome when a multicomponent measure of minority stress was used. This suggests the possibility that minority stress could impact different people in different ways, and that a multicomponent measure may capture these effects across individuals. Some of the studies we categorized as multicomponent measures involved experimental exposures that involved reflections on past experiences of discrimination or rejection. These exposures included both social evaluation and recalling of these discrimination experiences. Future studies may wish to consider multicomponent measures and begin to unpack if different components have different impacts for different people.

Analyses examining structural stigma and prejudice events and conditions (when outlying studies with large numbers of analyses were excluded) in relation to biological outcomes also had a relatively high rate of detection of associations. Elements of minority stress with lower proportions of associations included expectations of discrimination (around one in 10 analyses), and concealment of identity and internalized stigma (around one in 3 analyses). Expectations of discrimination and rejection may have been less likely to evidence an associationdue to the ways in which it was operationalized, for example as related to expected discrimination in a specific setting (i.e., in health care settings) rather than across settings, or through stigma consciousness (i.e., expectations of being stereotyped and rejected by others as in Caceres et al., 2022). Although these measures captured cognitions about the prevalence of stereotypes or presence of stigma in a specific context, they may not capture the degree of heightened threat activation in response to one’s position in a stigmatizing environment.There have not been very many measures available to capture expectations of discrimination or rejection, but these measures are becoming more available with scales such as the Negative Expectations for the Future Events subscale of the GMSR (Testa et al., 2015). Other constructs related to expectations of discrimination and prejudice that were not measured in the studies captured by this review include rejection sensitivity, hypervigilance, threat reactivity, stereotype threat, and threatened social safety attributed to SGM status. Alterations to threat reactivity and fear learning specific to minority stress may also be suited to be assessed with experimental methods. For example, threat-related emotional Stroop tasks Williams et al., 1996) or startle reactivity in response to stigma-related stimuli as in Mereish & Miranda Jr. (2021) may be effective measures of anticipatory minority stress, though more work is needed to develop minority stress-specific paradigms. However, experimental designs that intentionally expose SGM or other marginalized groups to minority stressors or related stimuli should be ethically considered, with the benefit of knowledge gained carefully weighed against participant experience.

When looking at overall categories of types of outcomes that evidenced an association with minority stress, sleep and immune outcomes had the highest proportion of analyses detecting an association, both with more than half of analyses detecting an association. Hormonal outcomes also evidenced a high proportion of associations, which may have been underestimated due to the total number of analyses run within those studies (e.g., testing associations at each time point within studies utilizing longitudinal cortisol measurement). Cardiovascular outcomes also had a high proportion of analyses evidencing an association. Metabolic outcomes had the lowest proportion of analyses evidencing an association. Epigenetic and transcriptional regulation outcomes tested here utlized epigenome and transcriptome wide data to generate an estimate of overall cellular or accelerated aging or adversity response, rather than examining epigenome or transcriptome wide associations. The Conserved Transcriptional Response to Adversity utilized in two studies is focused on a specific set of genes relevant to an immune and inflammation response to adversity (Cole, 2019). Future studies may benefit from investigating epigenomic or transcriptomic data across the epigenome or transcriptome, in order to link yet unidentified associations with minority stress. Such work may improve understanding of the molecular underpinnings of observed biological outcomes (e.g., examining epigenome changes related to immune function) to increase specificity and better elucidate impacts on biological functions.

Recommendations for Next Directions

The results of this review suggest there are several areas for future investigation to identify how minority stress may be altering the biological cascade. First, studies that utilize experimental methods, either of minority stress exposure (as captured in this review) or of the undoing of the impacts of minority stress through intervention (as in Flentje et al., In press, not captured in this review), may help us to better understand the mechanisms of minority stress in relation to the biological cascade. Here, we found that sleep and immune function seem particularly promising areas for future research. This review found multicomponent measures of minority stress, measures of prejudice and discrimination, and structural stigma may be key areas for future research on biological outcomes.

While we still have work to do to identify the most replicable predictors and outcomes, there are several considerations for future work. One challenge identified in this review is that, despite evidence of associations between minority stress and a wide range of biological outcomes, there are still frequent null results. Unpacking and understanding the role of moderators and full or partial mediators of these associations may yield more replicable results. Our model of the biological impacts of minority stress proposes several suggestions of important moderators and full or partial mediators including biological, psychological, social, behavioral, and structural factors (Figure 3). Accounting for these factors in our work will help us to understand both their independent impacts on the biological outcomes of study, and how their presence alters or accounts for the impact of minority stress on an individual’s biology.

Figure 3.

Theoretical model of biological processes of minority stress and clinicial outcomes among sexual and gender minority people

Several examples of moderators were identified in the articles located for our systematic review. Vincent et al. (2021) identified that concealment of one’s identity was related to kynurenine tryptophan ratio among SM men living with HIV — but only among White SM men and not SM men who were People of Color. This suggest that social (e.g., community support) or structural (e.g., racism or privilege) factors interact with the minority stress exposure to yield differences in the biological response. Similarly, Wood and Cook (2019) found that discrimination was related to C-Reactive Protein but only in the presence of low support from one’s father, suggesting that social context and experiences may alter the impact of minority stress.

Underlying biological processes independent of minority stress may also alter the impacts of minority stress on biology. For example, in two separate studies, enacted stigma (homophobic violence) was related to greater CTRA gene expression among Black and Latino SM men living without HIV (M. J. Li et al., 2020), but not associated with upregulated inflammatory gene expression among Black and Latino SM men living with HIV (M. J. Li et al., 2022). In this case, HIV may have already impacted inflammatory gene expression, altering the detectable signal related to minority stress specifically. In two other studies, effects were detected in men but not in women (i.e., structural stigma and allostatic load, Juster et al., 2024), or in women, but not men (i.e., (Oh et al., 2024). Differences by gender observed here could be social in nature or could be biological (i.e., differences in biological cascade of stress response based on hormonal milieu). There is evidence in the non-SGM literature for differences in general stress responses based on sex. For example, stress is thought to illicit greater inflammatory and depressogenic effects among females (Bekhbat & Neigh, 2018) with a shift to greater metabolic responses among females post menopause (Bourke et al., 2012). Among males, there is greater susceptibility to stress induced metabolic syndrome and metabolic stress responses among males (Bourke et al., 2012). Further, exposures to specific gonadal hormones may alter the stress response, for example testosterone inhibits the HPA axis (Chan et al., 2018). Transgender men who use testosterone evidence a change in metabolic markers that appears similar to cisgender men (Chan et al., 2018), thus may experience biological stress responses more similarly to cisgender men or postmenopausal women. Our review found that studies are now including GM people, but these studies did not exclusively investigate these processes among subgroups of GM people. Future work may clarify how sex and gender may mediate stress responses. Future studies with GM populations may help unpack how hormonal exposures or alterations in hormonal exposures (e.g., through gender affirming interventions) may alter stress responses.

Some intervening factors may be mediators or partial mediators depending on the outcome of interest. For example, (Gibbs, 2023) found that substance use partially mediated the association between microaggressions and sleep disturbance. In a separate study, (Gibbs & Fusco, 2023) found no association between several elements of minority stress and sleep disturbance, as the associations were mediated by both anxiety and perceptions of stress (psychological processes). Identifying and testing these important moderators or partial or total mediators will help isolate the effects of minority stress on biology. Some investigators consider these factors as covariates, which may also be an important approach to isolating the effects of minority stress. For instance, in Ghanooni et al., (2022), substance use was covaried in analyses that found an association between minority stress and accelerated epigenetic aging. Key moderators or potential full or partial mediators for investigation may include biological processes (e.g, hormonal exposures, substance use exposures, disease processes such as HIV), psychological processes (e.g., coping approaches, posttraumatic stress processes, depression, anxiety, substance use), social processes (e.g., parent support, community support), behaviors (e.g., exercise, meditation, substance use), exacerbation of the impacts of minority stress processes through psychological symptoms (e.g., trauma, anxiety, or depression symptoms), or other structural predictors (e.g., structural racism or economic or resource access or limitations) that may alter the impacts of minoirity stress and/or each in turn may create their own biological cascade. These moderators and mediators may also yield fruitful targets for interventions to reduce the impacts of minority stress.

Limitations

There are several limitations to this study. First, while technological advances have been made to allow for more rapid systematic review such as software that we used here, current systematic review software is better designed for clinical trial review. While we were able to count analyses for each type of minority stress and outcome, organizing the review at an analysis per analysis level across all of our metrics was not readily available. This means that studies that were categorized in more than one way (e.g., crossectional and longitudinal, self-report and objectively measured) would have results at the unit of analysis captured in both of these sections. We also did not capture all articles that tested the association between minority stress and a biological outcome. For example, physical health was not specifically one of our search terms, as our search terms (available in Supplemental Material 1) and guiding theoretical models, as in Flentje et al., (2020) and Figure 3, focused on biological processes relevant to minority stress, while overall physical health reflects a gestalt of these biological processes. As such, during full text review we retained articles that included overall physical health as an outcome, as it met our inclusion criteria, but we most certainly did not capture all articles on this topic, as evidenced by the Author’s own article (Flentje et al., 2021) which was not yielded through our search processes and which tested and detected associations between all elements of minority stress and structural stigma and overall physical health. It is also unknown to what extent publication bias is present in the larger literature, with null findings less likely to be reported than those where statistical association among variables are documented (i.e., file drawer effect). Further, in this review we did not estimate the sizes of the observed effects. We initially set out to do so, but found that effect sizes were not uniformly reported and available from the publications identified here. Similarly, due to a lack of uniform reporting of both research results and sample demographics, we provided our best estimates of our understanding of the research results, which may not have precisely captured the author’s procedures or results or the complete demographic characteristics of all samples.

Summary

This review replicates what we knew before: minority stress is associated with biological outcomes and processes. In this review, we extended results to demonstrate that these associations are also evident in GM populations. Areas evidencing promise for future research include studies that incorporate multiple components of minority stress exposure and studies examining prejudice events and conditions and structural stigma. Sleep and immune response are promising biological outcomes for future inquiry. Further, studies that incorporate experimental designs may help us to identify more replicable results. Finally, we are at the point where we must consider the important moderators and mediators of the association between minority stress and biological outcomes.