Discordance in chromosomal and self-reported sex in the UK Biobank: Implications for transgender- and intersex-inclusive data collection.

There is growing need to distinguish between sex and gender. While sex is assigned at birth, gender is socially constructed and may not correspond to one's assigned sex. However, in most research studies, sex or gender is assessed in isolation or the terms are used interchangeably, which has implications for research accuracy and inclusivity. We used data from the UK Biobank to quantify the prevalence of disagreement between chromosomal and self-reported sex and identify potential reasons for discordance. Among approximately 200 individuals with sex discordance, 71% of discordances were potentially explained by the presence of intersex traits or transgender identity. The findings indicate that when describing sex- and/or gender-specific differences in health, researchers may be limited in their ability to draw conclusions regarding specific sex and/or gender health information.

Update in Adult Transgender Medicine.

Transgender people often face barriers in health care due to lack of access to care, lack of knowledgeable healthcare professionals, discrimination, and gaps in medical and mental health research. Existing research on transgender health has focused heavily on mental health, HIV/AIDS, sexually transmitted diseases/infections, and substance abuse. Gender-affirming hormone therapy and/or surgery allows for some alignment of biology and gender identity. Gender-affirming care may offer quality-of-life benefits, which may outweigh modest concerns related to exogenous hormone therapy. The Endocrine Society treatment guidelines were revised in 2017, and this article reviews recent data that might inform a future guideline revision. Future longitudinal research is needed to close the gap in knowledge in the field of transgender medicine.

Gender-Affirming Care of Transgender and Gender-Diverse Youth: Current Concepts.

Increasing numbers of transgender and gender-diverse (TGD) youth, from early puberty through late adolescence, are seeking medical services to bring their physical sex characteristics into alignment with their gender identity-their inner sense of self as male or female or elsewhere on the gender spectrum. Numerous studies, primarily of short- and medium-term duration (up to 6 years), demonstrate the clearly beneficial-even lifesaving-mental health impact of gender-affirming medical care in TGD youth. However, there are significant gaps in knowledge and challenges to such care. Long-term safety and efficacy studies are needed to optimize medical care for TGD youth.

Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

Syphilis Prevalence, Incidence, and Demographic Differences in a Longitudinal Study of Young Sexual and Gender Minority Adults Assigned Male at Birth.

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.

Prevalence of Sexually Transmitted Infections Among Transgender Women With and Without HIV in the Eastern and Southern United States.

BACKGROUND: Data on the epidemiology of sexually transmitted infections (STIs) among transgender women (TGW) with and without human immunodeficiency virus (HIV) are limited. METHODS: We analyzed baseline data collected from a cohort of adult TGW across 6 eastern and southern US cities between March 2018 and August 2020 (n = 1018). Participants completed oral HIV screening, provided self-collected rectal and urogenital specimens for chlamydia and gonorrhea testing, and provided sera specimens for syphilis testing. We assessed associations with ≥1 prevalent bacterial STI using modified Poisson regression. RESULTS: Bacterial STI prevalence was high and differed by HIV status: 32% among TGW with HIV and 11% among those without HIV (demographic-adjusted prevalence ratio = 1.91; 95% confidence interval = 1.39-2.62). Among TGW without HIV, bacterial STI prevalence differed by geographic region, race and ethnicity, and gender identity, and was positively associated with reporting >1 sexual partner, hazardous alcohol use, homelessness, having safety concerns regarding transit to health care, and no prior receipt of gender-affirming health services. Among TGW with HIV, older age was inversely associated with bacterial STI. CONCLUSIONS: TGW had a high prevalence of bacterial STIs. The prevalence and correlates of bacterial STI differed by HIV status, highlighting the unique needs and risks of TGW with and without HIV. Tailored interventions may reduce sexual health-related inequities.

Transgender healthcare: metabolic outcomes and cardiovascular risk.

Transgender identity is often associated with gender dysphoria and minority stress. Gender-affirming hormone treatment (GAHT) includes masculinising or feminising treatment and is expected to be lifelong in most cases. Sex and sex hormones have a differential effect on metabolism and CVD in cisgender people, and sex hormone replacement in hypogonadism is associated with higher vascular risk, especially in ageing individuals. Using narrative review methods, we present evidence regarding metabolic and cardiovascular outcomes during GAHT and propose recommendations for follow-up and monitoring of metabolic and cardiovascular risk markers during GAHT. Available data show no increased risk for type 2 diabetes in transgender cohorts, but masculinising GAHT increases lean body mass and feminising GAHT is associated with higher fat mass and insulin resistance. The risk of CVD is increased in transgender cohorts, especially during feminising GAHT. Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit and increased BP, while feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol. Assigned male sex at birth, higher age at initiation of GAHT and use of cyproterone acetate are separate risk factors for adverse CVD markers. Metabolic and CVD outcomes may improve during gender-affirming care due to a reduction in minority stress, improved lifestyle and closer surveillance leading to optimised preventive medication (e.g. statins). GAHT should be individualised according to individual risk factors (i.e. drug, dose and form of administration); furthermore, doctors need to discuss lifestyle and preventive medications in order to modify metabolic and CVD risk during GAHT. Follow-up programmes must address the usual cardiovascular risk markers but should consider that biological age and sex may influence individual risk profiling including mental health, lifestyle and novel cardiovascular risk markers during GAHT.

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

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(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 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(ß) = 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(ß) = 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.

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia.

Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men's pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998-2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

Getting Precise about Gender and Sex Measurement: A Primer for Epidemiologists.

Accurately measuring gender and sex is crucial in public health and epidemiology. Iteratively reexamining how variables-including gender and sex-are conceptualized and operationalized is necessary to achieve impactful research. Reexamining gender and sex advances epidemiology toward its goals of health promotion and disease elimination. While we cannot reduce the complexities of sex and gender to simply an issue of measurement, striving to capture these concepts and experiences accurately must be an ongoing dialogue and practice-to the benefit of the field and population health. We assert that epidemiology must counteract misconceptions and accurately measure gender and sex in epidemiology. We aim to summarize existing critiques and guiding principles in measuring gender and sex that can be applied in practice.

Comparing Two-Step Approaches to Measuring Gender Identity: The Reliability and Applications of Asking About Sex Assigned at Birth versus Transgender Self-Identification.

Inclusive measures of gender are critical for health equity research. This study compared the reliability and applications of two different approaches for measuring gender in response to emerging community concerns regarding the potential harms of asking about sex assigned at birth (SAAB) within transgender and gender diverse (TGD) populations. Using data from a 2021 survey of LGBTQ+ people in Washington state, we compared approaches for measuring gender via a two-step question that collected data on: (1) current gender and SAAB versus (2) current gender and transgender self-identification. Among 2,275 LGBTQ+ participants aged 9-81, 63% were cisgender, 35% TGD, and 2% were not categorized. There was near perfect agreement between the two methods in their ability to identify TGD participants (percent agreement=99.7%, unweighted Cohen's Kappa=0.99). Among gender diverse participants, stratification by SAAB revealed differences in sexual health outcomes, while stratification by transgender self-identification revealed differences in access to gender-affirming care and lifetime experiences of discrimination. Ascertaining SAAB may be most useful for identifying sexual health disparities while transgender self-identification may better illuminate healthcare needs and social determinants of health among TGD people. Researchers and public health practitioners should critically consider the acceptability and relevance of SAAB questions to their research goals.

Prostate cancer in transgender women: A propensity score-matched analysis of disease severity and survival.

BACKGROUND: Despite the rise in gender-affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) remains in its infancy. Health disparities and lack of PCa awareness and screening are possible barriers to providing quality care for this population. In addition, the implication of hormonal manipulation for the aggressiveness of PCa in TGW is yet to be determined. Here, this study sought to compare oncological characteristics and survival outcomes between transgender and cisgender (CG) patients with PCa via two national data sets. METHODS: The Veterans Affairs Informatics and Computing Infrastructure database (1999-2020) and the Surveillance, Epidemiology, and End Results-Medicare database (2010-2017) were reviewed. Demographic and clinical details were analyzed. Logistic regression analysis was performed on propensity score-matched groups to identify predictors of high-risk disease and metastasis in patients with PCa. Groups were matched 5:1 (CG:TGW) on the basis of age, race, year of diagnosis, and Charlson Comorbidity Index score. Primary outcomes included metastatic presentation, high-risk localized disease, overall survival (OS), and prostate cancer-specific mortality (PCSM). RESULTS: A total of 1194 patients were included (199 TGW; 995 CG). Associations between transgender identity and metastatic presentation (odds ratio [OR], 0.38; p = .2), high-risk localized disease (OR, 1.19; p = .50), or PCSM (hazard ratio [HR], 0.65; p = .3) were not detected. Transgender identity was associated with improved OS (HR, 0.67; p = .014). CONCLUSIONS: PCa-specific outcomes seem comparable between TGW and CG men, although the study was underpowered to detect modest differences. Further investigation into the incidence and outcomes of PCa in TGW is warranted.

Cancer in people who identify as lesbian, gay, bisexual, transgender, queer, or gender-nonconforming.

BACKGROUND: Individuals who identify as lesbian, gay, bisexual, transgender, queer, intersex, or gender-nonconforming (LGBTQ+) experience discrimination and minority stress that may lead to elevated cancer risk. METHODS: In the absence of population-based cancer occurrence information for this population, this article comprehensively examines contemporary, age-adjusted cancer risk factor and screening prevalence using data from the National Health Interview Survey, Behavioral Risk Factor Surveillance System, and National Youth Tobacco Survey, and provides a literature review of cancer incidence and barriers to care. RESULTS: Lesbian, gay, and bisexual adults are more likely to smoke cigarettes than heterosexual adults (16% compared to 12% in 2021-2022), with the largest disparity among bisexual women. For example, 34% of bisexual women aged 40-49 years and 24% of those 50 and older smoke compared to 12% and 11%, respectively, of heterosexual women. Smoking is also elevated among youth who identify as lesbian, gay, or bisexual (4%) or transgender (5%) compared to heterosexual or cisgender (1%). Excess body weight is elevated among lesbian and bisexual women (68% vs. 61% among heterosexual women), largely due to higher obesity prevalence among bisexual women (43% vs. 38% among lesbian women and 33% among heterosexual women). Bisexual women also have a higher prevalence of no leisure-time physical activity (35% vs. 28% among heterosexual women), as do transgender individuals (30%-31% vs. 21%-25% among cisgender individuals). Heavier alcohol intake among lesbian, gay, and bisexual individuals is confined to bisexual women, with 14% consuming more than 7 drinks/week versus 6% of heterosexual women. In contrast, prevalence of cancer screening and risk reducing vaccinations in LGBTQ+ individuals is similar to or higher than their heterosexual/cisgender counterparts except for lower cervical and colorectal cancer screening among transgender men. CONCLUSIONS: People within the LGBTQ+ population have a higher prevalence of smoking, obesity, and alcohol consumption compared to heterosexual and cisgender people, suggesting a higher cancer burden. Health systems have an opportunity to help inform these disparities through the routine collection of information on sexual orientation and gender identity to facilitate cancer surveillance and to mitigate them through education to increase awareness of LGBTQ+ health needs.

Considerations in gender-affirming hormone therapy in transgender and gender diverse patients undergoing liver transplantation.

Liver transplantation is lifesaving for patients with end-stage liver disease. Similar to the role of transplantation for patients with end-stage liver disease, gender-affirming hormone therapy (GAHT) can be lifesaving for transgender and gender diverse (TGGD) patients who experience gender dysphoria. However, management of such hormone therapy during the perioperative period is unknown and without clear guidelines. Profound strides can be made in improving care for TGGD patients through gender-affirming care and appropriate management of GAHT in liver transplantation. In this article, we call for the transplant community to acknowledge the integral role of GAHT in the care of TGGD liver transplant candidates and recipients. We review the current literature and describe how the transplant community is ethically obligated to address this health care gap. We suggest tangible steps that clinicians may take to improve health outcomes for this minoritized patient population.

Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiolbaseline - serum estradiolfollow-up/study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

Breast and cervical cancer screenings across gender identity: results from the Behavioral Risk Factor Surveillance System before and during the COVID-19 pandemic.

PURPOSE: Although national medical organizations often neglect to include trans and gender diverse (TGD) people in their breast and cervical cancer screening recommendations, the World Profession Association of Transgender Health recommends that TGD people who are at risk for these cancers follow existing guidelines for cisgender women. Despite WPATH's recommendations, TGD people are less likely to get screened in large part due to discrimination. The COVID-19 pandemic has limited access to cancer screenings among cisgender people, but it is unknown how this has impacted TGD people. METHODS: Using national survey data from the Behavioral Risk Factors Surveillance System (BRFSS), we examined differences in cervical and breast cancer screening noncompliance across gender identity at two time points: before and during the COVID-19 pandemic. RESULTS: Screening noncompliance increased during the COVID-19 pandemic among cisgender and TGD people (e.g., transgender men, gender non-conforming people). Compared to cisgender women, transgender men and gender non-conforming respondents had higher odds of breast cancer screening noncompliance before and during COVID-19. Transgender men had lower odds of cervical cancer screening noncompliance than cisgender women before COVID-19, but higher odds during the pandemic. Gender non-conforming respondents also had lower odds of cervical cancer screening noncompliance during COVID-19 compared to cisgender women. CONCLUSIONS: Screening noncompliance for breast and cervical cancer was more common among TGD people than cisgender women; while these disparities existed before the COVID-19 pandemic, they were exacerbated during the pandemic. Future work should move beyond descriptive statistics and elucidate underlying causes to inform interventions.

Impact of Telemedicine on Access to Care for Rural Transgender and Gender-Diverse Youth.

OBJECTIVE: To explore the impact of telemedicine on access to gender-affirming care for rural transgender and gender diverse youth. STUDY DESIGN: A retrospective analysis of data drawn from the electronic medical records of a clinic that provides approximately 10 000 adolescent and young adult visits per year and serves patients seeking gender health care. The no-show rate was examined as a proxy for access to care due to anticipated challenges with recruiting a representative sample of a historically marginalized population. Logistic regression with generalized estimating equations was conducted to model the association between the odds of a no-show visit and covariates of interest. RESULTS: Telemedicine visits, rural home address, gender health visits, longer travel time, and being younger than 18 years old were associated with lower odds of a no-show in univariate models (n = 17 928 visits). In the adjusted model, the OR of no-shows for gender health visits was 0.56 (95% CI 0.42-0.74), adjusting for rurality, telemedicine, age (< or >18 years), and travel time to the clinic. CONCLUSIONS: In this study, telemedicine was associated with reduced no-shows overall, and especially for rural, transgender and gender diverse youth, and patients who hold both identities. Although the no-show rate does not fully capture barriers to access, these findings provide insight into how this vulnerable population may benefit from expanded access to telemedicine for rural individuals whose communities may lack providers with the skills to serve this population.

A Holistic Framework for the Evaluation of Kidney Function in a Gender-Diverse Landscape.

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females.

PURPOSE: Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axis of transgender subjects in an effort to throw light on this question. METHODS: Ten transgender males (TM) and eight transgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30 and 40 min. RESULTS: For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p < .05). Likewise, the overall SC response as calculated by the area under the curve was significantly lower (p = .0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p < .01) while ACTH-stimulated SC levels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p < .001). CONCLUSION: Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.

The experience of transfeminine adolescents and their parents regarding fertility preservation via testicular sperm extraction (TESE): a qualitative study.

STUDY QUESTION: How do transfeminine adolescents and their parents experience fertility preservation via testicular sperm extraction (TESE)? SUMMARY ANSWER: Participants experienced the TESE process positively when provided with appropriate guidance to navigate the decisional dilemma between preserving future biological parenthood and the pressure to start puberty suppression early. WHAT IS KNOWN ALREADY: Sperm banking through ejaculation is not feasible for all transfeminine adolescents due to genital dysphoria and early puberty; for this group, TESE is the only alternative. However, during early puberty, they must postpone or pause puberty suppression until spermatogenesis is fully developed. STUDY DESIGN, SIZE, DURATION: All consecutive TESE patients in our centre and their parents were invited to participate. Between December 2022 and May 2023, we included 6 adolescents and 10 parents. We used a qualitative approach based on semi-structured interviews to study the experience of the transfeminine adolescents and their parents. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transfeminine adolescents diagnosed with gender dysphoria in early puberty (Tanner stage ≥2) who underwent TESE before the start of puberty suppression or gender-affirming hormones participated in this study. The interviews were recorded, manually transcribed and analysed using reflective thematic analysis focusing on understanding the participants' experiences of puberty and fertility preservation and the various factors and social processes influencing their decision to undergo TESE. MAIN RESULTS AND THE ROLE OF CHANCE: Transfeminine adolescents decide to undergo invasive fertility preservation because of a possible, future desire for parenthood. Parents stressed the importance of preventing future decisional regret. They both saw masturbation to obtain a semen sample as unreachable. Even though TESE is a surgical procedure with possible complications and pain afterwards, this alternative seemed less dysphoric to them.Adolescents had to postpone the start of puberty suppression, waiting for spermatogenesis to complete. Given the unpredictable development of puberty, they felt a lot of stress and anxiety during this period and were primarily concerned about the lowering of their voice. Because of this puberty-related stress, they were constantly balancing their motivations for fertility preservation against the early start of puberty suppression to prevent unwanted irreversible pubertal body changes. To support this decisional dilemma, adolescents and their parents need adequate communication with each other and their healthcare providers to reflect on their stress for pubertal change. Furthermore, close, continuous surveillance of their current mental state by their parents, together with their psychologist and pubertal development by their physicians, is needed. Despite the challenging decision and postponement of puberty suppression, they retrospectively experienced it positively without any regret. LIMITATIONS, REASONS FOR CAUTION: All adolescents successfully underwent TESE, with viable spermatozoa obtained and without complications. This may result in a more positive reflective experience regarding fertility preservation. Furthermore, the perspectives of adolescents with the intention of TESE but who already started with puberty suppression before the preservation were not included. WIDER IMPLICATIONS OF THE FINDINGS: This study helps healthcare providers improve their counselling and guidance of transfeminine adolescents who consider postponing puberty suppression for fertility preservation via TESE. The adolescents and their parents know more clearly what to expect during fertility preservation. Specific peer-support programs may facilitate the decision process for upcoming adolescents. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. None of the authors have any conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.