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Background: Limited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts. Methods: Thirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT. Results: While alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism. Conclusions: This study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes. Trial registration: Clinicaltrials.gov NCT02185274. [ABSTRACT FROM AUTHOR]

Background: Gender dysphoria, characterized by a misalignment between one's gender identity and assigned sex, propels individuals towards medical interventions like gender reassignment surgery (GRS) to harmonize their bodies with their gender. This process aims to enhance overall quality of life (QoL), functioning, and body image. Recognizing the importance of cultivating a positive body image for transgender individuals navigating societal norms, this narrative highlights the ongoing debate surrounding QoL post-GRS. In response, our study is outlined, aiming to scrutinize QoL and self-image among transgender men post-GRS, offering valuable insights into societal perceptions and psychological well-being in this context. Method: This cross-sectional survey focused on transgender men aged 15 to 35 who underwent gender reassignment surgery (GRS) in 2018–2022 in Shiraz, Iran. Participants, after passing psychiatric evaluations, completed World Health Organization Quality of Life (WHOQOL-100) questionnaires pre- and at least one-year post-surgery. The scores of the Brief-WHOQOL questionnaire were evaluated in four domains of physical health, psychological health, social relationships, and environmental health. Results: A total of 60 individual who underwent GRS completed our questionnaire. The average age of the patients was 24.1 ± 3.8 years. Following GRS, the most increase was observed in the psychological factor (by 25.6%). The increase in score was statistically significant in all subgroups (P < 0.001) after operation. Urban living location had a significant association with higher increase in physical health (P < 0.010), psychological health (P = 0.005), and environmental health (P = 0.012) after GRS. In regards to physical health, the low socioeconomic group had a significantly less physical score improvement in QoL compared to the moderate group (P = 0.024) following GRS. In regards to environmental health, the high socioeconomic groups had significantly higher improvement in QoL compared to the low (P = 0.006) and moderate (P < 0.001) group after operation. Conclusion: The results demonstrate that GRS brings about improvements across all aspects of QoL. However, this enhancement is less pronounced among patients hailing from low socioeconomic backgrounds and rural areas. [ABSTRACT FROM AUTHOR]

Background: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). Methods: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. Results: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(β) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(β) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(β) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(β) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(β) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). Conclusions: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence. To address that, we conducted a gene expression analysis in female and male human spleen and identified the transmembrane protein CD99 as one of the most significantly differentially expressed genes with marked increase in men. CD99 has been reported to participate in immune cell transmigration and T cell regulation, but sex-specific implications have not been comprehensively investigated. Methods: In this study, we conducted a gene expression analysis in female and male human spleen using the Genotype-Tissue Expression (GTEx) project dataset to identify differentially expressed genes between women and men. After successful validation on protein level of human immune cell subsets, we assessed hormonal regulation of CD99 as well as its implication on T cell regulation in primary human T cells and Jurkat T cells. In addition, we performed in vivo assays in wildtype mice and in Cd99-deficient mice to further analyze functional consequences of differential CD99 expression. Results: Here, we found higher CD99 gene expression in male human spleens compared to females and confirmed this expression difference on protein level on the surface of T cells and pDCs. Androgens are likely dispensable as the cause shown by in vitro assays and ex vivo analysis of trans men samples. In cerebrospinal fluid, CD99 was higher on T cells compared to blood. Of note, male MS patients had lower CD99 levels on CD4+ T cells in the CSF, unlike controls. By contrast, both sexes had similar CD99 expression in mice and Cd99-deficient mice showed equal susceptibility to experimental autoimmune encephalomyelitis compared to wildtypes. Functionally, CD99 increased upon human T cell activation and inhibited T cell proliferation after blockade. Accordingly, CD99-deficient Jurkat T cells showed decreased cell proliferation and cluster formation, rescued by CD99 reintroduction. Conclusions: Our results demonstrate that CD99 is sex-specifically regulated in healthy individuals and MS patients and that it is involved in T cell costimulation in humans but not in mice. CD99 could potentially contribute to MS incidence and susceptibility in a sex-specific manner. Plain Language Summary: The immune system protects us from bacterial and viral infections and impacts the outcome of many diseases. Thus, understanding immunological processes is crucial to unravel pathogenic mechanisms and to develop new therapeutic treatment options. Sex is a biological variable affecting immunity and it is known that females and males differ in their immunological responses. Women mount stronger immune responses leading to more rapid control of infections and greater vaccine efficacy compared to men. However, this enhanced immune responsiveness is accompanied by female preponderance and susceptibility to autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis (MS). MS sex ratio varies around 2:1 to 3:1 with a steadily increasing incidence in female MS patients making sex one of the top risk factors for developing MS. However, the underlying biological mechanisms including sex hormones as well as genetic and epigenetic factors and their complex interplay remain largely unknown. Here, we discovered the gene and its encoded protein CD99 to be differentially expressed between women and men with men showing increased expression on many immune cell subsets including T cells. Since T cells are key contributors to MS pathogenesis, we examined the role of CD99 on T cells of healthy individuals and MS patients. We were able to identify CD99-mediated T cell regulation, which might contribute to sex differences in MS susceptibility and incidence indicating the importance to include sex as a biological variable. Of note, these differences were not reproduced in mice showing the necessity of functional research in humans. Highlights: Profiling of differential gene expression between sexes in the human immune system to delineate differential regulations that might impact immune responses. CD99 is genetically but not hormonally regulated on transcript and surface protein level with higher expression in men in healthy individuals as well as MS patients. Confirmation of CD99 as a critical co-stimulatory molecule on T cells, thus having an impact on T cell activation, proliferation and cluster formation. CD99 expression is elevated on T cells in the CSF compared to the blood. In male MS patients CD99 expression on CD4+ T cells from the CSF was lower in comparison to healthy men. Species difference in CD99 expression and its functional role with lack of differential CD99 expression in male and female mice as well as Cd99 deficiency not altering experimental autoimmune encephalomyelitis. [ABSTRACT FROM AUTHOR]

Background: Transgender individuals experience limited access to healthcare. This results not least from experiences of discrimination to which they are exposed in the health system. These contribute to transgender individuals having poorer health than cis individuals, i.e. individuals whose sex assigned at birth is in line with their gender identity. It is an ethical duty to take effective measures to minimize inequalities in medical care. At best, such measures should also be assessed as appropriate from the perspective of those affected in order to be accepted and thus effective. It is therefore important to know whether measures touch on the subjectively assumed reasons for experiences of discrimination. Hence, to be able to take appropriate measures, it is important to identify the reasons that transgender individuals see as causal for their experiences of discrimination in healthcare. Methods: We conducted semi-structured interviews with 14 German transgender individuals and asked them about their own experiences of discrimination in healthcare and their assumptions on the reasons for discrimination. We analyzed the responses using the method of structured qualitative content analysis. Results: 13 transgender individuals reported experiences of discrimination in healthcare. These emanated from different professional groups and took place in trans-specific as well as general medical settings. We were able to identify a total of 12 reasons that transgender individuals see as causal for their experiences of discrimination: (1) internalized trans-hostility and "protection" of cis individuals, (2) lack of knowledge/uncertainties regarding transition, (3) "protection" of a binary worldview, (4) binary worldview in medicine, (5) structural deficits, (6) asymmetric interactions with specialists, (7) current political debate, (8) view of transgender individuals as a "burden for society", (9) objectification, (10) homophobia, (11) misogyny/androcentrism and (12) discrimination as reaction to discrimination. Conclusions: German transgender individuals have a very differentiated picture regarding their subjective reasons for experiencing discrimination in healthcare. Overall, disrespect regarding gender identity and a confrontation with foreignness seems to be seen as the decisive factor. Thus, it is not enough to focus only on measures that aim to remedy the information deficit on the part of medical providers. Measures must be taken that can create a granting and respectful attitude towards transgender individuals. [ABSTRACT FROM AUTHOR]

Background: Sexual orientation refers to a person's enduring emotional, romantic, or sexual attractions to other people. Sexual orientation measures do not typically consider desires for, or sexual behavior with, transgender people. We describe measures inclusive of transgender people and characterize sexual orientation identity, behavior, and attraction in a representative sample of the U.S. transgender population. Methods: Between April 2016-December 2018, a U.S. national probability sample of transgender (n = 274) and cisgender (n = 1,162) adults were invited to complete a self-administered web or mailed paper survey. We assessed sexual identity with updated response options inclusive of recent identity terms (e.g., queer), and revised sexual behavior and attraction measures that included transgender people. Multiple response options were allowed for sexual behavior and attraction. Weighted descriptive statistics and sexual orientation differences by gender identity groups were estimated using age-adjusted comparisons. Results: Compared to the cisgender population, the transgender population was more likely to identify as a sexual minority and have heterogeneity in sexual orientation, behavior, and attraction. In the transgender population, the most frequently endorsed sexual orientation identities were "bisexual" (18.9%), "queer" (18.1%), and "straight" (17.6%). Sexually active transgender respondents reported diverse partners in the prior 5 years: 52.6% cisgender women (CW), 42.7% cisgender men (CM), 16.9% transgender women (TW), and 19.5% transgender men (TM); 27.7% did not have sex in the past 5 years. Overall, 73.6% were "somewhat"/ "very" attracted to CW, 58.3% CM, 56.8% TW, 52.4% TM, 59.9% genderqueer/nonbinary-females-at-birth, 51.9% genderqueer/nonbinary-males-at-birth. Sexual orientation identity, behavior, and attraction significantly differed by gender identity for TW, TM, and nonbinary participants (all p < 0.05). Conclusions: Inclusive measures of sexual orientation captured diverse sexual identities, partner genders, and desires. Future research is needed to cognitively test and validate these measures, especially with cisgender respondents, and to assess the relation of sexual orientation and health for transgender people. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this systematic review and meta-analysis was to synthesize the literature on eating disorders and eating disorder symptomatology among transgender individuals and to summarize the existing literature on gender-affirming treatment and the prevalence of eating disorder symptomatology. Method: The literature search for this systematic review and meta-analysis was performed in PubMed, Embase.com, and Ovid APA PsycInfo. We searched for "eating disorders" and "transgender" using both controlled vocabularies and natural language terms for their synonyms. The PRISMA statement guidelines were followed. Quantitative data from studies on transgender individuals and eating disorders assessed with relevant assessment tools was included. Results: Twenty-four studies were included for the qualitative synthesis, and 14 studies were included in the meta-analysis. The results revealed higher levels of eating disorder symptomatology among transgender individuals compared with cisgender individuals, especially cisgender men. Transgender men tend to display higher levels of eating disorder symptomatology than transgender women; however, transgender women seem to have higher levels of eating disorder symptomatology than cisgender men and, interestingly, this study also noted a trend toward transgender men having higher levels of eating disorders than cisgender women. Gender-affirming treatment seems to alleviate the presence of eating disorder symptomatology in transgender individuals. Discussion: The body of research on this subject is extremely limited, and transgender individuals are underrepresented in the eating disorder literature. More research investigating eating disorders and eating disorder symptomatology in transgender individuals and the relationship between gender-affirming treatment and eating disorder symptomatology is needed. Plain English Summary: Research has found that transgender individuals are more likely to be diagnosed with an eating disorder or to engage in disordered eating than cisgender individuals. The purpose of this systematic review and meta-analysis was to synthesize the literature on eating disorders and eating disorder symptomatology among transgender individuals and to summarize the existing literature on gender-affirming treatment and the prevalence of eating disorder symptomatology. The literature search for this systematic review and meta-analysis was performed in online databases. Quantitative data from studies on transgender individuals and eating disorders assessed with relevant assessment tools was included. The results revealed higher levels of eating disorder symptomatology among transgender individuals compared with cisgender individuals, especially cisgender men. Gender-affirming treatment seems to alleviate the presence of eating disorder symptomatology in transgender individuals. The body of research on this subject is extremely limited, and transgender individuals are underrepresented in the eating disorder literature. [ABSTRACT FROM AUTHOR]

Background: Testosterone may be a possible modifiable risk factor for open-angle glaucoma (OAG) and intraocular pressure (IOP), but evidence has been scarce and conflicting. In this study we evaluated the association of testosterone and its genetic predisposition with incident (i) OAG, IOP, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GCL +). Methods: Participants aged 45–100 years were derived from the prospective, population-based Rotterdam Study. Ophthalmic examinations and serum testosterone measurements (including bioavailable and free testosterone) were performed from 1991 onwards. Follow-up took place every 4–5 years. A total of 187 out of 7898 participants were diagnosed with incident (i) OAG during follow-up. Genotyping was performed in 165 glaucoma cases and 6708 controls. We calculated sex-specific weighted genetic risk scores (GRS) for total and bioavailable testosterone. Associations with iOAG were analyzed using multivariable logistic regression. Associations with IOP, RNFL, and GCL + were analyzed with multivariable linear regression. Analyses were stratified on sex and adjusted for at least age, body mass index, and follow-up duration. Results: In men, testosterone was not associated with iOAG. However, the GRS for higher total testosterone was associated with an increased iOAG risk (odds ratio [OR] with 95% confidence interval [95% CI]: 2.48 [1.18; 5.22], per unit). In women, higher values of bioavailable testosterone (2.05 [1.00; 4.18] per nmol/L) and free testosterone (1.79 [1.00; 3.20] per ng/dL) were significantly associated with increased risk of iOAG. Moreover, the GRS for higher bioavailable testosterone was associated with an increased iOAG risk (2.48 [1.09; 5.65], per unit). Higher bioavailable and free testosterone were adversely associated with IOP (0.58 [0.05; 1.10] per nmol/L and 0.47 [0.04; 0.90] per ng/dL). Higher total testosterone was inversely associated with peripapillary RNFL and GCL + (Beta [95% CI]: − 3.54 [− 7.02; − 0.06] per nmol/L and − 2.18 [− 4.11; − 0.25] per nmol/L, respectively). Conclusions: In women, higher testosterone levels increased the risk of iOAG. Both IOP-dependent and IOP-independent mechanisms may underlie this association. Managing testosterone levels may be particularly relevant for the prevention of neurodegeneration in the eye. Future research should confirm these findings. Highlights: Higher testosterone levels are associated with an increased incidence of open-angle glaucoma (OAG) in women, but not in men. In women, a genetic predisposition to develop higher levels of testosterone showed similar associations, internally validating our findings. In women, we observed an adverse association of testosterone levels with intraocular pressure (the main risk factor of OAG) as well as an inverse association with the retinal nerve fiber layer (thinned in OAG cases). Hereby, we confirmed the association between testosterone and OAG in women in an independent manner. These findings are important since the number of gender dysphoric individuals seeking hormonal therapy is increasing and OAG is a common sight-threatening disorder. If any, transgender men receiving testosterone therapy may have an increased risk of OAG. [ABSTRACT FROM AUTHOR]

Background: Although discriminatory experiences of transgender people seeking healthcare services have been well-documented in several studies, differentiating those experiences based on gender identity/expression and related factors has been limited. The aim of this study was to compare the characteristics, experiences, attitude, and expectation toward accessing healthcare service and healthcare providers of transgender women and transgender men in Thailand. Methods: A cross-sectional study was conducted from October 2017 to March 2018. The data were collected from transgender women and transgender men aged ≥ 18 years old who lived in Thailand using online platform via different websites and Facebook pages of local transgender group. Binary logistic regression was used to identify the factors related to the study outcomes. Results: Of 186 transgender people who responded to the questionnaire and were eligible for the study, 73.7% (95% confidence interval [CI] = 66.7–79.8) were transgender women and 26.3% (95% CI = 20.2–33.3) were transgender men. Transgender women were more likely to seek general healthcare from non-traditional healthcare services (crude odds ratio [cOR] = 4.28; 95% CI = 1.55–11.81; P = 0.005), buy hormone treatment from non-traditional healthcare services (cOR = 3.89; 95% CI = 1.18–12.83; P = 0.026), and receive healthcare counseling from non-traditional healthcare providers (cOR = 5.16; 95% CI = 1.42–18.75; P = 0.013) than transgender men. According to the results of applying a multivariable model, transgender respondents who did not know that gender-affirming healthcare services existed in Thailand were more unwilling to receive counseling from gender-affirming healthcare providers than those who did (adjusted odds ratio = 3.70; 95% CI = 1.11–12.36; P = 0.033). Conclusions: The findings from this cross-sectional study indicate that transgender women are more likely than transgender men to receive general healthcare and hormone treatment from non-traditional healthcare services and buy hormone treatment without a physician's supervision. We also found approximately 15% of transgender individuals who did not receive gender-affirming counseling services. Continuing to improve access to care for the transgender community, increasing public relations channels may encourage transgender people to access more healthcare services. [ABSTRACT FROM AUTHOR]

Background: While there is growing research considering the experiences of transgender youth whose identities align with the gender binary, especially among young trans women, there are significantly fewer studies that accurately capture data about nonbinary youth, and even fewer studies capturing the experiences of transgender and gender diverse (TGD) youth of color. The purpose of this research was to assess the prevalence of sexual health behaviors, mental health challenges, substance use, and healthcare utilization among Black/African American, Latinx, Asian/Pacific Islander, indigenous and multi-racial/ethnic TGD youth, who have been largely underrepresented in research. Methods: A total of 108 TGD youth ages 16–24 were recruited into the Trans Youth of Color Study (TRUTH). Each participant completed a 90-min survey administered by a research assistant with more sensitive information collected using ACASI. In addition to a completing a survey administered by research staff, participants also participated in specimen collection, which included urine sampling to assess recent substance use without a prescription, self-collected rectal/frontal and throat swabs to test for gonorrhea and chlamydia, and a blood draw to test for recent use of drugs, gonorrhea and chlamydia, and syphilis. The sample was recruited at public venues, community outreach and referral, through social media outreach, and via participant referral. Cross-sectional analyses were from a single study visit. Results: Compared to rates among their cisgender peers, participants reported experiencing adverse social and structural determinants of health—e.g. food insecurity (61%), housing instability (30%), and limited access to healthcare (26% had no place to go for healthcare)—and elevated rates of illicit drug use (19–85%), mental health problems (e.g. 60% self-reported depression), and involvement in sexual risk-related behaviors (e.g. among those reporting penetrative sex 57–67% reported sex without a condom). Conclusions: This study adds descriptions of both mental and sexual health outcomes of a non-clinical sample of TGD youth to the literature, particularly among young transgender men and gender nonbinary youth, who have frequently been excluded from previous studies of sexual health. The findings document experiences and behaviors among TGD youth that contribute to mental and sexual health concerns, including rates of substance use, and healthcare utilization. [ABSTRACT FROM AUTHOR]

Background: Over 1.4 million US adults identify as transgender when gender identity differs from the sex assigned at birth [1]. Although transgender patients face adverse health outcomes, they remain an understudied population [2]. A 2017 study surveyed 411 practicing clinicians and found that 80% had been involved in treating a transgender patient, but 80.6% had never received training on transgender care [3]. The purpose of this report is to describe prolonged desaturation in one case of a transgender patient who wore a chest binder intraoperatively owing to a lack of preoperative recognition.Case Presentation: A 19-year-old transgender male of African-American descent with anxiety and class 3 obesity presented for an esophagogastroduodenoscopy to evaluate a 2-year history of upper abdominal pain unresponsive to proton pump inhibitor therapy, with a plan for monitored anesthesia care. His medications included sertraline, pantoprazole, zolpidem, ergocalciferol, leuprolide, and testosterone cypionate. Preoperatively, the patient was instructed to remove all clothing and to don a patient gown while in the bathroom. The attending anesthesiologist then conducted the interview and examination in the preoperative holding area. The patient was induced with 250 mg of propofol, and reassuring respirations were noted by capnography. Respirations and oxygen saturation remained stable upon insertion of the endoscope. Four minutes later, the patient's oxygen saturation rapidly decreased to 50% and end-tidal capnography was lost. The endoscope was removed, and the patient was given 200 mg of propofol and 20 mg succinylcholine. His oxygen saturation recovered to 80% and 100% after 2 and 5 minutes, respectively, of ventilation with 100% inspired oxygen. No further oxygen desaturation was noted throughout the procedure, and the patient was closely monitored for signs of respiratory difficulty during an uneventful postoperative course. After full emergence, it was revealed that the patient had been wearing a chest binder throughout the operative procedure. The patient was counseled on the necessity to communicate the presence of this accessory prior to all future procedures.Conclusion: In the clinical narrative, a healthy patient was observed to have prolonged oxygen desaturation after induction of anesthesia. Laryngospasm was suspected clinically owing to the sudden absence of end-tidal carbon dioxide. Prolonged oxygen desaturation despite appropriate interventions suggests the contribution of additional factors. We speculate that the presence of a chest binder intraoperatively predisposed the patient to more rapid oxygen desaturation less responsive to typical therapy. A chest binder would introduce mechanical restriction to the patient's breathing owing to its inherent design to compress. Although the patient was asked to remove all clothing, specific instructions were not provided regarding the removal of a chest binder. The presence of chest binding was also absent in the electronic health record, despite the documented presence of the patient's preferred gender, hormonal therapy regimen, and medical history. Ultimately, this case reflects the gap between practitioner knowledge and hospital guidelines and the practices of transgender patients. In reviewing existing literature and the potential for atelectasis with external compression, we would consider that patients refrain from chest binding for 12-24 hours before surgical procedures, resume no sooner than 24 hours after ambulation, and participate in diagnostic incentive spirometry pre- and postoperatively. [ABSTRACT FROM AUTHOR]

Background: Understanding and addressing healthcare and service delivery inequalities is essential to increase equity and overcome health disparities and service access discrimination. While tremendous progress has been made towards the inclusion of sexual and gender minorities in health and other research, gaps still exist. Innovative methods are needed to close these. This case study describes and reflects on using online-based data collection to ascertain sexual health decision-making and health service utilisation among Kenyan queer womxn and trans men.Methods: Case study The study used a mixed-methods approach in two phases with triangulated quantitative and qualitative elements. Both elements used web-based technology to gather data.Results: Using online spaces to recruit and collect data from queer womxn and trans men exceeded expectations. A total of 360 queer womxn and trans men responded to the digitally distributed survey, and 33 people, queer womxn and trans men, as well as key informants, participated in the interviews, which were primarily conducted on Zoom and Skype. The case study analyses the risks and benefits of this approach and concludes that online sampling approaches can mitigate risks and enable effective and safe sampling of a marginalised group in a restrictive legal setting: Kenyan queer womxn and trans men.Conclusion: Using online spaces when researching marginalised populations could effectively overcome risks around stigma, discrimination and violence. It could be an effective way to understand these populations' healthcare needs better. Factors contributing to success included building trusting relationships with key members of the community, strategic and opportune timing, a nuanced understanding of the mobile landscape, and carefully chosen safety and security measures. However, it should be noted that conducting research online could increase the risk of further marginalising and excluding those without access to web-based technology. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is an epigenetic mark that is influenced by underlying genetic profile, environment, and ageing. In addition to X-linked DNA methylation, sex-specific methylation patterns are widespread across autosomal chromosomes and can be present from birth or arise over time. In individuals where gender identity and sex assigned at birth are markedly incongruent, as in the case of transgender people, feminization or masculinization may be sought through gender-affirming hormone therapy (GAHT). GAHT is a cornerstone of transgender care, yet no studies to date have investigated its effect on genome-wide methylation. We profiled genome-wide DNA methylation in blood of transgender women (n = 13) and transgender men (n = 13) before and during GAHT (6 months and 12 months into feminizing or masculinizing hormone therapy). Results: We identified several thousand differentially methylated CpG sites (DMPs) (Δβ ≥ 0.02, unadjusted p value < 0.05) and several differentially methylated regions (DMRs) in both people undergoing feminizing and masculinizing GAHT, the vast majority of which were progressive changes over time. X chromosome and sex-specific autosomal DNA methylation patterns established in early development are largely refractory to change in association with GAHT, with only 3% affected (Δβ ≥ 0.02, unadjusted p value < 0.05). The small number of sex-specific DMPs that were affected by GAHT were those that become sex-specific during the lifetime, known as sex-and-age DMPs, including DMRs in PRR4 and VMP1 genes. The GAHT-induced changes at these sex-associated probes consistently demonstrated a shift towards the methylation signature of the GAHT-naïve opposite sex, and we observed enrichment of previously reported adolescence-associated methylation changes. Conclusion: We provide evidence for GAHT inducing a unique blood methylation signature in transgender people. This study advances our understanding of the complex interplay between sex hormones, sex chromosomes, and DNA methylation in the context of immunity. We highlight the need to broaden the field of 'sex-specific' immunity beyond cisgender males and cisgender females, as transgender people on GAHT exhibit a unique molecular profile. [ABSTRACT FROM AUTHOR]

Background: Transgender men are a marginalized population with unique health care needs. However, their usage of health services is low because of considerable discrimination. A major factor in their avoidance is patient-provider interactions. Methods: This cross-sectional study included 102 transgender men who anonymously completed a 55-item questionnaire in clinic, between 10/2017 and 01/2019. In addition, 92 transgender women filled out the part about family physician's preferences. We examined which characteristics transgender men prefer in their obstetricians/gynecologists in order to promote their usage of healthcare services. Results: A small majority of the transgender men (54.1%) had no gender preference for their obstetrician/gynecologist, while 42.9% preferred a female obstetrician/gynecologist and 3.1% preferred a male obstetrician/gynecologist. Most transgender men with a same-gender preference preferred female obstetricians/gynecologists for both invasive procedures (e.g., pelvic examination, 97.4%) and non-invasive procedures (e.g., cesarean section, 60%). The reasons for preferences regarding invasive procedures were feeling comfortable, embarrassment and feeling that female obstetricians/gynecologists are gentler. Transgender men who preferred female obstetricians/gynecologists ranked ability (90.5%), sexual tolerance (92.9%) and gender identity tolerance (90.5%) as the top three desirable qualities of obstetricians/gynecologists, while the responders who did not prefer female ranked ability (94.6%), experience (92.9%) and knowledge (92.9%) as the top three qualities. Transgender men with female preferences considered female obstetricians/gynecologists to be more accepting of gender identity compared to the responders that did not prefer females (47.5% vs. 9.1%, P <.001).. Conclusion: A small majority of the transgender men exhibited no gender preference when choosing an obstetrician/gynecologist, although 42.9% preferred females. The latter choice was associated with the assumption that female obstetricians/gynecologists are more tolerant towards their transgender men patients. Educating the medical staff about their special needs and establishing dedicated SGM centers staffed with high percentages of female healthcare providers are highly recommended. [ABSTRACT FROM AUTHOR]

Background: Vitrification has superseded the slow freezing method for cryopreservation of oocytes, embryos, and sperm, but there are as yet no standard protocols for its use in ovarian tissue cryopreservation (OTC). Published protocols diverge mainly with regard to the extent of supplementation of dimethyl sulfoxide (DMSO) to the vitrification medium, and to the use of an open or closed vitrification system. We investigated the viability of cells after vitrification/warming, using ovarian tissue of transgender patients, by means of Fluorescence Activated Cells Sorting (FACS), and histomorphological analyses using a DMSO-containing (P1) and a DMSO-free protocol (P2) in an open or closed vitrification setting. Results: Twelve ovarian samples were donated from female-to-male transgender patients: 6 were vitrified according to protocol 1, the other 6 according to protocol 2. The amount of viable cells was 90.1% (P1) and 88.4% (P2) before vitrification. After vitrification and subsequent warming, viable cells were reduced to 82.9% (P1, p = 0.093) and 72.4% (P2, p = 0.019). When comparing the closed and the open systems, the decline in cell viability from pre- to post-vitrification was significant only for the latter (p = 0.037). Histological examination reveals no significant differences with respect to degenerated follicles before or after vitrification. Conclusion: These results led us to conclude that a protocol containing DMSO results in a higher viability of ovarian cells than a protocol that uses ethylene glycol as cryoprotective agent in vitrification. The use of an open vitrification system led to significant decline in the rate of viable cells. Trial registration: NCT03649087, retrospectively registered 28.08.2018. [ABSTRACT FROM AUTHOR]

Background: In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown.Methods: In this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system.Results: Ovaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis).Conclusions: Our novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary. [ABSTRACT FROM AUTHOR]

Purpose: Representing the pathological extreme pursuit of muscularity, muscle dysmorphia (MD) is characterized by a pervasive belief or fear around insufficient muscularity and an elevated drive for muscularity. Despite evidence of heightened body image-related concerns among gender minority populations, little is known about the degree of MD symptoms among gender minorities, particularly based on Muscle Dysmorphic Disorder Inventory (MDDI) scores. The objective of this study was to assess community norms of the MDDI in gender-expansive people, transgender men, and transgender women. Method: Data from participants in The PRIDE Study, an existing study of health outcomes in sexual and gender minority people, were examined. We calculated means, standard deviations, and percentiles for the MDDI total and subscale scores among gender-expansive people (i.e., those who identify outside of the binary system of man or woman; n = 1023), transgender men (n = 326), and transgender women (n = 177). The Kruskal-Wallis test was used to assess group differences and post hoc Dunn's tests were used to examine pairwise differences. Results: Transgender men reported the highest mean MDDI total score (30.5 ± 7.5), followed by gender-expansive people (27.2 ± 6.7), then transgender women (24.6 ± 5.7). The differences in total MDDI score were driven largely by the Drive for Size subscale and, to a lesser extent, the Functional Impairment subscale. There were no significant differences in the Appearance Intolerance subscale among the three groups. Conclusions: Transgender men reported higher Drive for Size, Functional Impairment, and Total MDDI scores compared to gender-expansive people and transgender women. These norms provide insights into the experience of MD symptoms among gender minorities and can aid researchers and clinicians in the interpretation of MDDI scores among gender minority populations. Plain English summary: Transgender people have a gender identity or expression that differs from what is typically associated with the sex assigned to them at birth. Gender-expansive refers to gender identities that do not fit within the binary (woman/man) gender system. We asked gender-expansive people, transgender men, and transgender women in The PRIDE Study to fill out a widely used survey about muscle dysmorphia, a condition in which a person worries they are not muscular enough. The results showed that transgender men had the highest muscle dysmorphia symptoms, followed by gender-expansive people, then transgender women. These findings can help clinicians and researchers in interpreting a survey assessing muscle dysmorphia in gender-expansive people, transgender men, and transgender women. Characterizing muscle dysmorphia symptoms in these populations is an important step to improve mental wellness among transgender and gender-expansive people. [ABSTRACT FROM AUTHOR]

Purpose: Gender-expansive individuals (i.e., those who identify outside of the binary system of man or woman) are a marginalized group that faces discrimination and have a high burden of mental health problems, but there is a paucity of research on eating disorders in this population. This study aimed to describe the community norms for the Eating Disorder Examination Questionnaire (EDE-Q) in gender-expansive populations. Methods: The participants were 988 gender-expansive individuals (defined as neither exclusively cisgender nor binary transgender) from The PRIDE study, an existing longitudinal cohort study of health outcomes in sexual and gender minority people. Results: We present the mean scores, standard deviations, and percentile ranks for the Global score and four subscale scores of the EDE-Q in this group as a whole and stratified by sex assigned at birth. Gender-expansive individuals reported any occurrence (≥1/28 days) of dietary restraint (23.0%), objective binge episodes (12.9%), excessive exercise (7.4%), self-induced vomiting (1.4%), or laxative misuse (1.2%). We found no statistically significant differences by sex assigned at birth. Compared to a prior study of transgender men and women, there were no significant differences in eating attitudes or disordered eating behaviors noted between gender-expansive individuals and transgender men. Transgender women reported higher Restraint and Shape Concern subscale scores compared to gender-expansive individuals. Compared to a prior study of presumed cisgender men 18–26 years, our age-matched gender-expansive sample had higher Eating, Weight, and Shape Concern subscales and Global Score, but reported a lower frequency of objective binge episodes and excessive exercise. Compared to a prior study of presumed cisgender women 18–25 years, our age-matched gender-expansive sample had a higher Shape Concern subscale score, a lower Restraint subscale score, and lower frequencies of self-induced vomiting, laxative misuse, and excessive exercise. Conclusions: Gender-expansive individuals reported lower Restraint and Shape Concern scores than transgender women; higher Eating, Weight, and Shape Concern scores than presumed cisgender men; and lower Restraint but higher Shape Concern scores than presumed cisgender women. These norms can help clinicians in treating this population and interpreting the EDE-Q scores of their gender-expansive patients. [ABSTRACT FROM AUTHOR]

Sex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences in cardiovascular disease states. This review focuses on how the effects of testosterone on arterial vessels impact the female vasculature. In women with androgen-excess polycystic ovary syndrome, and in transgender men, testosterone exposure is associated with high blood pressure, endothelial dysfunction, and dyslipidemia. These relationships suggest that androgens may exert pathophysiological effects on the female vasculature, and these effects on the female vasculature appear to be independent from other co-morbidities of cardiovascular disease. There is evidence that the engagement of androgens with androgen receptor induces detrimental outcomes in the female cardiovascular system, thereby representing a potential causative link with sex differences and cardiovascular regulation. Gender affirming hormone therapy is the primary medical intervention sought by transgender people to reduce the characteristics of their natal sex and induce those of their desired sex. Transgender men, and women with androgen-excess polycystic ovary syndrome both represent patient groups that experience chronic hyperandrogenism and thus lifelong exposure to significant medical risk. The study of testosterone effects on the female vasculature is relatively new, and a complex picture has begun to emerge. Long-term research in this area is needed for the development of more consistent models and controlled experimental designs that will provide insights into the impact of endogenous androgen concentrations, testosterone doses for hormone therapy, and specific hormone types on function of the female cardiovascular system. [ABSTRACT FROM AUTHOR]

No guidelines exist regarding nutrition assessment for transgender or gender non-conforming patients. Multiple nutrition assessment methods utilize gender-specific values that provide distinct recommendations for males and females. This clinical case series depicts the food and nutrition considerations of ten adult transgender men using anthropometric, survey, and dietary recall data. Male reference values were used to analyze patient data, though multiple approaches to nutrition assessment in the transgender population are discussed. Major nutrition-related concerns were obesity, low fruit and vegetable intake and high sodium intake; disordered eating was not a prominent concern. Further research is needed to inform nutrition care for the transgender and gender non-conforming populations. [ABSTRACT FROM AUTHOR]

Background: Some transgender men retain their uterus, get pregnant, and give birth. However, societal attitudes about gender have erected barriers to openly being pregnant and giving birth as a transgender man. Little research exists regarding transgender men's reproductive needs. Anecdotal observations suggest that social change and increasing empowerment of transgender men may result in increasing frequency and openness about pregnancy and birth. Specific needs around conception, pregnancy, and newborn care may arise from transphobia, exogenous testosterone exposure, or from having had (or desiring) gender-affirming surgery. We undertook a qualitative study to understand the needs of transgender men who had given birth.Methods: We interviewed 10 transgender men who had been recruited for a recently published online cross-sectional survey of individuals (n = 41). Subjects had given birth while identifying as male. Interviews were recorded, transcribed, and systematically coded. Analysis used a priori and emergent codes to identify central themes and develop a framework for understanding participant experiences.Results: Participants reported diverse experiences and values on issues including prioritization and sequencing of transition versus reproduction, empowerment in healthcare, desire for external affirmation of their gender and/or pregnancy, access to social supports, and degree of outness as male, transgender, or pregnant. We identified structural barriers that disempowered participants and describe healthcare components that felt safe and empowering. We describe how patients' strategies, and providers' behaviors, affected empowerment. Anticipatory guidance from providers was central in promoting security and empowerment for these individuals as patients.Conclusions: Recognizing diverse experiences has implications in supporting future patients through promoting patient-centered care and increasing the experiential legibility. Institutional erasure creates barriers to transgender men getting routine perinatal care. Identifying this erasure helps shape recommendations for how providers and clinics can provide appropriate care. Specific information regarding reproduction can be helpful to patients. We provide recommendations for providers' anticipatory guidance during the pre-transition, pre-conception, prenatal, and postpartum periods. Ways to support and bring visibility to the experience of transgender men are identified. Improving clinical visibility and affirming gender will likely enhance patient experience and may support patient-centered perinatal healthcare services. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer, nearly all cases of which are caused by one of several high-risk strains of the human papillomavirus (hr-HPV), leads to significant morbidity and mortality in individuals with a cervix. Trans masculine (TM) individuals were born with female reproductive organs and identify as male, man, transgender man, or another diverse gender identity different from their female assigned sex at birth. Routine preventive sexual health screening of TM patients is recommended, including screening for cervical cancer and other sexually transmitted infections (STIs); however, as many as one in three TM patients are not up-to-date per recommended U.S.Guidelines: Among cisgender (non-transgender) women, self-swab hr.-HPV DNA testing as a primary cervical cancer screening method and self-swab specimen collection for other STIs have high levels of acceptability. No study has yet been conducted to compare the performance and acceptability of self- and provider-collected swabs for hr.-HPV DNA testing and other STIs in TM patients.Methods: This article describes the study protocol for a mixed-methods biobehavioral investigation enrolling 150 sexually active TM to (1) assess the clinical performance and acceptability of a vaginal self-swab for hr.-HPV DNA testing compared to provider cervical swab and cervical cytology, and (2) gather acceptability data on self-collected specimens for other STIs. Study participation entails a one-time clinical visit at Fenway Health in Boston, MA comprised of informed consent, quantitative assessment, venipuncture for syphilis testing and HIV (Rapid OraQuick) testing, randomization, collection of biological specimens/biomarkers, participant and provider satisfaction survey, and qualitative exit interview. Participants are compensated $100. The primary study outcomes are concordance (kappa statistic) and performance (sensitivity and specificity) of self-collected vaginal HPV DNA specimens vs provider-collected cervical HPV swabs as a gold standard.Discussion: This study addresses critical gaps in current clinical knowledge of sexual health in TM patients, including comparing alternative strategies for screening and diagnosis of cervical cancer, hr.-HPV, and other STIs. Findings have implications for improving the delivery of sexual health screening to this often overlooked and underserved patient population. Less-invasive patient-centered strategies may also generalize to other at-risk cisgender female populations that face barriers to timely and needed STI and cervical cancer screening.Trial Registration: ClinicalTrials.gov ID: NCT02401867. [ABSTRACT FROM AUTHOR]

Background: Gender-affirming hormone therapy has been hypothesized to reduce the patient's reproductive potential in transmen, although the exact long-term effects on future fertility are unknown. Methods: In this prospective cohort study we aimed to evaluate ovaries of 20 transmen by using hormone serum levels, histomorphological analysis and fluorescence activated cells sorting (FACS) analysis – in order to assess the amount of vital cells. Results: The median total number of follicles per field of view was 39 (IQR 12–122). Of all follicles (n = 1661), the vast majority was primordial (n = 1505, 90.6%), followed by primary (n = 76, 4.6%), abnormal (n = 63, 3.8%) and secondary follicles (n = 17, 1.0%). FACS analysis was available for 13 samples (65.0%) and the median frequency of vital cells was 87.5% (IQR, 77.7–95.4%). Both a higher age (p = 0.032) and a lower BMI (p = 0.003) were significantly associated with a higher frequency of vital cells. Conclusion: The majority of ovarian cells after long-term androgen treatment were vital in FACS analysis and histomorphological evaluation revealed a normal cortical follicle distribution. These results are currently exploratory, but might be promising for issues on fertility preservation. Trial registration: The study was approved by the ethics committee of the Medical University of Vienna (EK 2240/2016) and was retrospectively registered in the Current Controlled Trials Register (registration number NCT03649087, date of registration: 28.08.2018). [ABSTRACT FROM AUTHOR]