Gender-affirming Therapy Research Articles

The Effects of Perioperative Gender-affirming Hormone Therapy on Facial Feminization Surgery Adverse Events, Facial Features Addressed, and Esthetic Satisfaction: A Multimodal Analysis.

Facial feminization surgery (FFS) treats gender dysphoria in transfeminine patients by addressing the facial bony and soft tissue components. Individuals seeking FFS may be taking gender-affirming hormone replacement therapy [gender-affirming hormone therapy (GAHT)]. This study aims to better characterize the GAHT's impact on venous thromboembolism (VTE) risk, surgical planning, and outcomes. A systematic review and meta-analysis of the literature were carried out to assess the effect of perioperative GAHT continuation on VTE. Cochrane Q and I2 statistics measured study heterogeneity with the following meta-regression exploring these results. Simultaneously, a retrospective review of the senior author's FFS cohort was conducted to investigate GAHT duration's impact on FFS revision rate, complication incidence, and facial structures operated on. Eleven articles were included: 602 patients stopped GAHT, of whom 3 VTEs were recorded (0.49%). This is compared with one episode among the 925 who continued GAHT perioperatively (0.11%). Study heterogeneity was low (0%), but limited VTE sample size precluded meta-analytic conclusions. Gender-affirming hormone therapy duration does not impact the incidence of all-cause complications (P = 0.478), wound infection (P = 0.283), hematoma (P = 0.283), or VTE (P = 1). The only procedures significantly less associated with higher GAHT were tracheal shaving (P = 0.002) and mandibuloplasty (P = 0.003). Finally, the FFS revision rate was not associated with GAHT duration (P = 0.06). There is a paucity of data to assess the safety or harm of continuing GAHT in the FFS perioperative period. Thus, a shared provider-patient decision-making process examining the risks and benefits of GAHT perioperative continuation is warranted. As patients seeking gender-affirming care are diverse, a "one-protocol-fits-all" is not appropriate.

05 The experience of youth on the waitlist for gender-affirming care in Manitoba

Abstract Background Waitlist times are often two years for youth to be seen for initial assessment for gender-affirming hormone therapy in Manitoba, Canada. It is well known that transgender youth awaiting hormone therapy have high rates of mental health challenges, including depression, anxiety, and suicidal ideation. Accessing care that is affirming and supportive, including primary care and counselling, can also be a challenge. Objectives The purpose of this study was to understand the experiences of youth and their caregivers on the waitlist for the Winnipeg, Manitoba-based Gender Diversity Affirmation and Action for Youth (GDAAY) clinic, the provincial transgender health clinic. Specifically, we were interested in what community based resources youth were accessing, mental health impacts, and suggestions for improvements. Design/Methods Qualitative, semi-structured interviews were conducted. Youth aged 14-17 years on the waitlist for 12-24 months for gender-affirming hormone therapy assessment and their caregivers were recruited. Separate interviews were conducted for youth and their caregivers. All interviews were virtual, recorded, and transcribed prior to thematic analysis. Results Youth (n=8) and caregivers (n=9) described barriers to supported transition. The first theme, “In a Black Hole” describes frustration and disappointment with the lack of regular ongoing communications from GDAAY. It also extends to the mental health challenges faced by youth and caregivers alike. Anxiety and self-harm were consistently described, with caregivers volunteering more information on self-harm and suicidality than youth. Youth described dysphoria and two youth found alternative providers for hormone therapy while on the waitlist. Our second theme, “Structural Transphobia”, describes the attitudinal, technological, physical, and architectural barriers faced by the participants. For example, one caregiver described a hospital admission for suicide attempt during which the hospital bracelet displayed the wrong gender, the wrong name, contributing to frequent mis-gendering. Frustration with the inability to change the name and gender marker in provincial charting systems was similarly of concern. Our final theme, “Manitoba: An Information Desert” describes the systemic barriers faced including lack of knowledgeable providers and reliable information within the province. Youth and caregivers described concerns with identifying primary care and councilors that understood challenges specific to transgender youth. Conclusion Although delays in gender-affirming therapy were noted, youth socially transitioned and accessed existing resources. However, mental health concerns persisted and participants felt frustrated and unsupported during their extensive wait times. Improved experiences may be achieved by additional communication from the clinic, hands-on assistance with accessing relevant resources, and an improved online presence. Potential competing interests Funding was obtained by a resident research small grant from the University of Manitoba. A similar abstract was submitted to CPEG but it focuses on a new intervention of a phone call from social work when a youth is added to the waitlist.

7978 Metabolic Outcomes in Transgender Youth Receiving Affirming Hormonal Therapy

Abstract Disclosure: M. Salama: None. R. Basmaci: None. T. Rajjo: None. O. Chuzhyk: None. A.N. Lteif: None. A. Al Nofal: None. Objective: Heightened societal acceptance of transgender youth and increased awareness of their unmet medical needs have led to a rise in referrals for hormonal therapy. There is limited literature available on the metabolic outcomes of hormone therapy on transgender youth. We investigated how the different metabolic markers of cardiovascular disease change after the initiation of gender-affirming hormonal therapy in transgender adolescents. Methods: A Retrospective, observational cohort study based on chart review of all children with gender dysphoria (under 18 years of age) who were evaluated in the Pediatric Endocrinology Clinic in a tertiary care center between January 2015 and December 2022. Children's demographic information, baseline weight, height, BMI, hematocrit, lipid profile, ALT, prolactin, and HbA1C levels were obtained before and after the initiation of gender-affirming hormonal therapy. The Wilcoxon signed-rank test was employed for paired analysis, while the chi-square test was used as appropriate. Results: We identified 106 transgender youth who were included in the analysis, with a median age at the start of hormonal therapy of 16 years (IQR: 15-17); comprising 68 trans-males (64%) and 38 trans-females (36%). The median treatment duration was 34 months (IQR: 18-54). Among trans-males, ALT levels increased post-treatment (mean difference 6.851 U/L, p < 0.001), as did BMI Z scores (mean difference 0.257, p < 0.001) and LDL-C (mean difference 12.734 mg/dl, p = 0.002), triglycerides (mean difference 10.18 mg/dl, p = 0.009), non-HDL-C (mean difference 12.8 mg/dl, p = 0.002), and total cholesterol (mean difference 10.18 mg/dl, p = 0.02). No significant differences were observed in HbA1C and HDL-C post-treatment. Among transfemales, BMI Z-scores were higher post-treatment (mean difference 0.27, p = 0.007), with increased total cholesterol (mean difference 19.88 mg/dl, p = 0.008), LDL-C (mean difference 12.6 mg/dl, p = 0.02), and HDL-C (mean difference 11.38 mg/dl, p < 0.001). Other variables did not significantly differ pre-and post-treatment. Ten transfemales with measured prolactin levels pre- and post-treatment showed no statistically significant differences. Conclusion: This pilot study revealed increased BMI Z scores following the commencement of hormone therapy in both trans-male and trans-female youths. Moreover, masculinizing treatment led to increased ALT levels. Furthermore, the cardiometabolic profile exhibited diverse alterations, particularly higher LDL-C levels in both cohorts. These findings underscore the necessity for close monitoring of these parameters during the treatment of transgender youth. Larger prospective randomized controlled trials are essential to comprehensively assess the impact of gender-affirming therapy on transgender youth. Presentation: 6/2/2024

Slipped Capital Femoral Epiphysis in an Adolescent Undergoing Gender-Affirming Therapy with a Gonadal-Releasing Hormone Analog

Case: Physeal stability in slipped capital femoral epiphysis (SCFE) depends on integrity of the hypertrophic zone. This in turn is affected by imbalance between circulating growth hormones and gonadal hormones. This case describes the occurrence of SCFE in a Māori (indigenous New Zealander) transgender girl, undergoing gender-affirming therapy with a gonadal-releasing hormone analog (GnRHa). Conclusion: Surgeons and clinicians alike should be aware that GnRHa in gender-affirming therapy may confer an additional risk factor, lowering the threshold required for SCFE to occur. Counseling patients about potentially increased risk, and need for timely presentation could be warranted, particularly in high-risk individuals.

Disparities in access to fertility preservation among adolescents undergoing gonadotoxic therapies.

Fertility preservation (FP) for adolescents prior to potentially gonadotoxic therapies is not accessible for all patients. Current literature acknowledges multiple barriers to FP, but research surrounding disparities for accessing these services is limited. We aimed to identify inequities in receiving FP services among adolescents undergoing gonadotoxic therapy. A retrospective chart review was performed at a single academic medical center for patients aged 0-21 referred for FP counseling prior to gonadotoxic therapy. Exclusions included referral after treatment, prior to gender-affirming therapy, or for fertility discussion due to a genetic condition. Minority patients were defined as non-White race and/or Hispanic ethnicity. Non-minority patients were defined as White, non-Hispanic. Analyses to assess differences in receiving FP based on minority identity and insurance status were performed via logistic regression, with receiving desired care as the outcome variable. Our cohort included 136 patients-38 minority and 98 non-minority. Forty-six (33.8%) patients had Medicaid, which did not differ between minority and non-minority (42.1% vs. 38.8%, P = .73). Most patients (83.1%) had a cancer diagnosis. Similar proportions of minority and non-minority patients had gonadotoxic treatment starting urgently (52.6% vs. 55.1%, P = .80), while more minority than non-minority patients desired FP (89.5% vs .77.5%, P = .10). When controlling for insurance type and age, minority participants were 12.8% less likely to receive desired FP (marginal effect = - .128, P = .05). This study identified significant inequities for minority populations in accessing FP. Further research is needed to determine how to make FP services more accessible to all patients, regardless of minority status.

Immune system adaptation during gender-affirming testosterone treatment

Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID1, similar to observations in other infections2. Females respond more strongly to vaccines, and adverse reactions are more frequent3, like most autoimmune diseases4. Immunological sex differences stem from genetic, hormonal and behavioural factors5 but their relative importance is only partially understood6–8. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.

Navigating gender dysphoria: A comprehensive review and therapeutic insights

Gender dysphoria (GD) is defined as an experiencing of practical dissatisfaction with one’s anatomical sex and/or primary gender and the gender that the person is sexually assigned at birth, which causes considerable emotional distress. This review aims to unravel the various dimensions of GD focusing in its diagnosis, genetic and environment factors and treatment. GD presents in different demographics of the population and is associated with other psychological symptoms such as anxiety, depression or social isolation. Like most chronic diseases, the causes of GD are not yet fully understood because even though genetics may be involved, more detailed studies are required. Existing therapies include hormone replacement therapy, surgical intervention, counseling and gender-affirmation therapy, intended to reduce distress in people with GD and to help them if they choose to transition. It also focuses on the exclusion of conversion therapy in the interest of supporting marginal gender’s expression and identity. The last precautions emphasize the relevance of further studies and the utilization of the extensive, scientific treatment approaches to enhance the quality of the life of patients with GD.

Is there an association between pelvic pain and gender-affirming testosterone therapy in trans masculine adolescents? An exploratory cross-sectional study

Background High rates of pelvic pain have been reported in trans individuals on testosterone, but the pathophysiology of pain and the potential role of testosterone are unclear. Aims The aim of this exploratory study was to determine whether the proportion of pelvic pain in trans adolescents is different among those on testosterone therapy compared to those who are not. Secondary objectives were to determine the characteristics, potential contributing factors, impact, and treatment of pelvic pain in trans adolescents. Methods An online cross-sectional study about pelvic pain was conducted among trans individuals assigned female at birth, aged 12 and over, and who had sought care at our institution since 2017. Results Among 102 participants, 79 (77.5%) reported having experienced pelvic pain over the last 6 months. The proportion of individuals who reported pelvic pain was lower in individuals on testosterone (n = 43/62, 69.4%) compared to those not on testosterone (n = 36/40, 90%), with a difference in proportion of −20.6% (95% CI −35.4 to −5.9%, p = 0.006). Half of participants reported school or work absenteeism and two thirds missed extracurricular activities because of pelvic pain. A wide range of treatment options were used, with variable rates of reported effectiveness. Conclusion Pelvic pain is frequently reported by trans adolescents. This exploratory study found a lower proportion of pelvic pain in trans adolescents using testosterone therapy compared to those who were not. Nevertheless, this study was limited by a small number of participants, its cross-sectional nature, and the risk of recruitment bias, thus limiting its generalizability. Longitudinal studies are required to better understand the development and evolution of pelvic pain in trans adolescents.

Physical Fitness and Exercise Performance of Transgender Women.

In spite of the evolving participation of transgender adults in exercise and sports, research investigating the physical fitness of transgender women remains scarce in the scientific literature. In this cross-sectional study, a variety of reference-standard measures of physical fitness of transgender women who had undergone gender-affirming orchiectomy (30 ± 4 years; n = 15) and who had not (27 ± 4 years: n = 15) were compared with reference males (28 ± 5 years; n = 15) and reference females (29 ± 5 years; n = 15) who were matched for age and estimated physical activity level. Transgender women had been undergoing feminizing gender-affirming therapy for 8-10 years. Height and lean mass of arms, legs, and trunk (measured via DXA) of transgender women were greater than those of reference females but lower than those of reference males (all p < 0.05). No significant differences were in isokinetic muscular torque found between reference females and transgender women. Both absolute and relative measures of maximal oxygen consumption were greater in reference males than in reference females and transgender women (all p < 0.05) with no significant difference between the latter two groups. Reference males had greater peak Wingate anaerobic power (expressed in both absolute and relative to body weight), countermovement jump, and squat jump than reference females and transgender women (all p < 0.05). There were no significant differences in anaerobic power between reference females and transgender women. The results on the field tests, including agility T-test and sprint running acceleration, were consistent with the anaerobic power tests. There were no statistical differences in any of the physical fitness measures between transgender women with and without orchiectomy. Transgender women demonstrated similar levels of reference-standard measures of physical fitness to females that were significantly lower than males.

Incidence of High Risk and Malignant Pathological Findings in Transgender and Gender Diverse Individuals Undergoing Gender-Affirming Mastectomy

BackgroundConcrete, data-driven guidelines for breast cancer screening among the transgender and gender diverse (TGD) population is lacking. The present study evaluates possible associations of gender-affirming hormone therapy (GAHT) on incidental breast pathology findings in trans-masculine patients to inform decision making about breast cancer screening.Patients and MethodsThis was a retrospective cohort study of patients who had gender-affirming mastectomy or breast reduction at a single center from July 2019 to February 2024. A total of 865 patients met the inclusion criteria. Gender-affirming testosterone therapy and length of exposure were evaluated to seek differences in post-operative pathology findings.ResultsThe median age at the time of surgery was 27 years [interquartile range (IQR) 21–30]. Most participants identified as female to male (658, 75.6%). A significant portion of the participants (688, 79.2%) were undergoing testosterone therapy at the time of surgery, with the median duration of testosterone use prior to surgery being 14 months (IQR 4–29). High risk or malignant findings were noted in pathology results for 12 of 1730 breasts (0.7%). Ordered logistic regression found that duration of testosterone therapy was not associated with increasing severity of incidental breast pathology. Additionally, patients under 25 years of age were 70% less likely to have any incidental finding on pathological evaluation than older patients [odds ratio (OR) 0.3, p < 0.01, confidence interval (CI) 0.18–0.50].ConclusionsThe present study found that patients undergoing GAHT should not be screened for breast cancer with increased frequency compared with cis-gender women. Additionally, it may be appropriate for trans women under the age of 25 with normal breast cancer risk to forego pathological breast tissue examination.

The Importance of Fertility Preservation in the Transgender Population

ObjectiveTo call to attention the often-overlooked aspect of pediatric transgender care: the importance of fertility preservation prior to instituting gender-affirming therapy. The transgender population has long been marginalized by society. Societal stigmata, fear to seek care, and dearth of provider knowledge regarding transgender health issues has caused disparities to widen. Gender affirming procedures and hormone therapy affect the long-term reproductive potential of transgender individuals. While cost concerns and insurance coverage regarding oncofertility is a prominent area of discussion, the transgender community is often excluded. MethodsSixteen genetically XY females, followed by their multidisciplinary transgender care teams, were interested in starting hormone therapy due to impending onset and/or progression of puberty. Their physicians were aware of fertility struggles after undergoing hormone therapy and therefore referred to urology. Sperm cryopreservation via open gonadal biopsy, testicular tissue cryopreservation (TTC), and semen sample (when age/maturity-appropriate) were discussed. Though requiring surgery, biopsy/TTC relieves patients of the psychological impact of semen sample production. ResultsUnder IRB approval, 15 patients (median age 12 years, range 10-16 years) underwent TTC (Figure 1). One patient (aged years) opted for semen sample. All patients had success with spermatogonial stem cells cryopreserved for future patient use. ConclusionsWith more individuals beginning medical and surgical therapy at a younger age, fertility preservation discussions are essential but often overlooked, depriving these individuals the joy of becoming a biological parent. TTC can be safely done in pediatric populations, though research is necessary to expand beyond current experimental stage of tissue-development.

Understanding the Role of Sex Hormones in Cardiovascular Kidney Metabolic Syndrome: Toward Personalized Therapeutic Approaches.

Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin-angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome.

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

BackgroundThe 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).MethodsOf 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.ResultsLonger 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).ConclusionsTT 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.

A comparative study of 3D measuring methods for monitoring breast volume changes

Three-dimensional (3D) imaging techniques are promising new tools for measuring breast volume, for example in gender-affirming therapy. Transgender individuals can be treated with gender-affirming hormone therapy (GAHT). A robust method for monitoring breast volume changes is critical to be able to study the effects of feminizing GAHT. The primary aim of this study was to compare the accuracy of three 3D devices (Vectra XT, Artec LEO and iPhone XR) for measuring modest breast volume differences using a mannequin. The secondary aim of this study was to evaluate these methods in several performance domains. We used reference prostheses of increasing volumes and compared the volumes using GOM-inspect software. For Vectra XT 3D images, manufacturer-provided software was used to calculate volumes as well. The scanning methods were ranked based on their performance in a total of five categories: volume estimations, costs, user-friendliness, test subject-friendliness and technical aspects. The 3D models analyzed with GOM-inspect showed relative mean estimate differences from the actual volumes of 9.1% for the Vectra XT, 7.3% for the Artec LEO and 14% for the iPhone XR. For the Vectra XT models analyzed with the built-in software this was 6.2%. Root mean squared errors (RMSE) calculated based on the GOM-inspect volume analyses showed mean RMSEs of 2.27, 2.54 and 8.93 for the Vectra XT, Artec LEO and iPhone XR, respectively. The Vectra software had a mean RMSE of 3.00. In the combined performance ranking, the Vectra XT had the most favorable ranking, followed by the Artec LEO and the iPhone XR. The Vectra XT and Artec LEO are the preferred scanners to monitor breast development due to the combination of higher accuracy and overall performance. The current study shows that 3D techniques can be used to adequately measure modest breast volume differences and therefore will be useful to study for example breast changes in transgender individuals using feminizing GAHT. These observations may also be relevant in other fields of 3D imaging research.

Making a Statement: Positions of Professional Medical Organizations Towards Gender-Affirming Care.

Despite politically charged media coverage and legislation surrounding gender affirming care (GAC), many organizations have released position statements to provide scientifically backed clinical practice standards, combat misinformation, and inform medicolegal policies. The purpose of this study is to objectively assess the availability and the content of the official position statements of relevant medical professional organizations regarding GAC. A list of U.S. medical professional organizations with likely involvement in GAC based on medical or surgical specialties was compiled. For included organizations, we evaluated the availability, content, and publication year of positions on GAC through October 2023. When available, formal positions were categorized as supportive or unsupportive. A total of 314 professional medical organizations were screened for our study based on specialty, relevance to GAC, and issuance of patient guidelines or position statements. Inclusion criteria were met by 55 organizations. Most organizations (35, 63.6%) had formal position statements on GAC. Support for GAC was described in 97.1% (n=34). Further, 94.2% (n=33) of available statements explicitly addressed GAC in individuals less than 18 years old and were largely supportive (96.9%, n=32). This cross-sectional analysis demonstrates that a majority of multidisciplinary professional medical organizations with relevance to GAC have issued formal position statements on the topic. Available positions were overwhelmingly supportive of individualized access to gender-affirming therapies in adult and adolescent populations. However, silence from some organizations continues to represent a modifiable disparity in the provision of GAC.

Impact of sex used for assignment of reference intervals in a population of patients taking gender-affirming hormones

BackgroundGender-affirming hormone therapy with either estradiol or testosterone for transgender persons can significantly impact chemistry and hematology laboratory tests. The sex used for assignment of reference intervals (RIs) in the electronic health record (EHR) will influence normal/abnormal flagging of test results. ObjectiveTo analyze common non-hormonal laboratory tests with sex-specific RIs ordered in patients with sexual orientation/gender identify (SOGI) field differences (one or more differences between legal sex, sex assigned at birth, and gender identity) in the EHR at an academic medical center in midwestern United States. MethodsWe utilized a previously characterized data set of patients at our institution that included chart review information on gender identity and gender-affirming therapy. We focused on the subset of these patients that had orders for 18 common laboratory tests in calendar year 2021. ResultsA total of 1336 patients with SOGI field differences (1218 or 91.2% identifying as gender-expansive; 892 or 66.8% receiving estradiol or testosterone as gender-affirming therapy) had a total of 9374 orders for 18 laboratory tests with sex-specific RIs. Hemoglobin, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and high-density lipoprotein were the most frequently ordered tests. For patients taking estradiol, 128 of 970 (13.2%) creatinine and 39 of 193 (20.2%) hemoglobin measurements were within the RI for one sex but not the other. For those taking testosterone, 119 of 531 (22.4%) creatinine and 49 of 120 (40.8%) hemoglobin measurements were within the RI for one sex but not the other. Values above the cisgender female RI but within the cisgender male RI were common for hemoglobin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in patients taking testosterone. ConclusionsClinicians should be aware of the potential impact of gender-affirming therapy on laboratory tests and what sex/gender is being used in the EHR to assign RIs.

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.

Transsexual men and pregnancy: an integrative literature review.

Promoting sexual and reproductive health in the context of transmasculinity constitutes a new issue for health service organisation. This integrative review sought to understand the current evidence on pregnancy in transsexual men in the context of sexual and reproductive health care. From a search of the BVS, PubMed, Science Direct, Scopus, Capes, SciELO and PEPSIC databases, from 2010 to 2020, a sample of 11 articles was selected, treated by content analysis and grouped into four analytical categories: health services - positive experiences; cis heteronormative health services; implications of pregnancy for transsexual bodies; and repercussions of gender-affirming therapy and pregnancy. A cis heteronormative logic was found to predominate in health care, leading to negative experiences during antenatal care and childbirth among transsexual men. Their unique health needs during the pregnancy-puerperium cycle should include mental health care. It is suggested that strategies be adopted to build capacity in health professionals with a view to respectful, inclusive perinatal care for this population group, as well as further studies on the subject.

A Gender-Affirming Approach to Fertility Care for Transgender and Gender-Diverse Patients

Although many transgender and gender-diverse (TGD) people express a desire to become parents, providing quality counseling that encompasses patients' short-term and long-term fertility options often represents a challenge for health care professionals. Fertility care (from preservation to restoration or assisted reproduction or both) has a low uptake in the TGD population, with barriers including financial cost, concerns regarding health care professionals’ biases, and patient misconceptions or lack of awareness of fertility outcomes. Fertility care is particularly important for the TGD population, because gender-affirming hormone therapy can negatively affect fertility. Despite this importance, existing guidelines and research on this subject are limited. This article summarizes the currently available fertility care options for TGD patients and provides our clinical opinion on their best provision. We highlight that it is essential for health care professionals to provide TGD patients with holistic counseling to facilitate informed decision making about their reproductive health before initiating gender-affirming therapy. Fertility counseling should outline the options available for the patient, keeping their needs and preferences at the center of the conversation while advising on the associated risks and financial costs.

Caring for the Older Transgender Adults: Social, Nursing, and Medical Challenges.

Aging is a challenging process for people with gender nonconformity. Indeed, the older transgender population faces several disparities in accessing and using health care and social support services. Furthermore, the clinical management of gender transition in later life is empirical since clear research evidence is lacking. This paper aimed to present the problems encountered by older transgender adults in their access to social support and health care and to propose insightful solutions to address them both from a social and medical/nursing perspective. Trans elders face profound disparities in health and social care due to factors associated with limited accessibility to health services, social restrictions, administrative failures, and physical vulnerabilities. The medical treatment of older transgender adults also needs a careful approach to achieve satisfying gender affirmation without clinically significant risks. The potential induction of hormone-sensitive malignancies and the provocation of major adverse vascular events are the main concerns. Gender transition in older adults without a prior history of following gender-affirming therapy is challenging due to biological factors related to advanced age. Caring for elderly trans people unfolds at multiple levels. International organizations and governmental bodies should address the underprivileged status of elderly transgender people by creating and implementing inclusive policies. Safe and respectful clinical and residential environments and the formation of clearer medical guidelines could meet the unique needs of older trans adults. Care providers must advocate for their patients and be equipped to provide safe and effective services.