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Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization.Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38).Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups.Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices.

In this mixed-methods quality improvement project, we implemented and evaluated sexual orientation and gender identity (SOGI) form rollout in the electronic medical record. Families in our gender diversity program completed a baseline survey in 2017 (55/328 responded) and follow-up in 2020 (180/721 responded) to evaluate the frequency of affirmed name and pronoun use in the hospital. Survey feedback informed system-wide inclusivity efforts and training. SOGI was implemented in 2020 after 1,662 providers completed an online training and 11,090 team members completed gender and sexual orientation inclusivity training. We recommend similar trainings for health systems utilizing SOGI.

Context Crinecerfont, a corticotropin-releasing factor type 1 (CRF1) receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD CAH), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated ACTH. Objective To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH. Design Open-label, phase 2 study (NCT04045145). Setting United States (4 centers). Participants Males and females, 14 to 17 years of age, with classic 21OHD CAH. Intervention Orally administered crinecerfont (50 mg twice daily) for 14 consecutive days with morning and evening meals. Main outcomes Change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. Results Eight participants (3 males, 5 females) were enrolled; mean age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, -57.1%; 17OHP, -69.5%; and androstenedione, -58.3%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone. Conclusions Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.

Liver disease in children with Turner Syndrome (TS) is poorly understood relative to associated growth, cardiac and reproductive complications. This study sought to better characterize hepatic abnormalities in a large national cohort of youth with TS.Using electronic health record data from PEDSnet institutions, 2145 females with TS were matched to 8580 females without TS on eight demographic variables. Outcomes included liver enzymes (AST and ALT) stratified as normal, 1-2 times above the upper limit of normal (ULN), 2-3 times ULN and 3 times ULN, as well as specific liver disease diagnoses.Fifty-eight percent of youth with TS had elevated liver enzymes. Patients with TS had higher odds of enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), 2-3 times ULN (OR: 2.7, 95% CI: 1.7-3.3) and 3 times ULN (OR: 1.7, 95% CI: 1.3-2.2). They also had higher odds of any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0) and liver tumour/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In a multinomial model, age, BMI and presence of cardiovascular disease or diabetes significantly increased the odds of elevated liver enzymes in girls with TS.Youth with TS have higher odds for elevated liver enzymes and clinically significant liver disease compared with matched controls. These results emphasize the need for clinical screening and additional research into the aetiology and treatment of liver disease in TS.Turner Syndrome, a chromosomal condition in which females are missing the second sex chromosome, is often associated with short stature, infertility and cardiac complications. Liver abnormalities are less well described in the literature. In this study, nearly 60% of youth with TS have elevated liver enzymes. Furthermore, patients with TS had a diagnosis of liver disease more often than patients without TS. Our results support the importance of early and consistent liver function screening and of additional research to define mechanisms that disrupt liver function in paediatric TS females.

Study Objective: Based on updated guidelines and expressed patient needs, we created a multidisciplinary clinic including endocrinology, gynecology/adolescent medicine, dermatology, psychology, and nutrition to provide comprehensive care to adolescent girls with polycystic ovary syndrome (PCOS). We describe the patient population presenting to this clinic, and prescribing patterns when a multidisciplinary approach is used. Design: Retrospective chart review. Setting: Tertiary care hospital. Participants: Female patients, aged 11-24 years, presenting for initial assessment in a multidisciplinary PCOS clinic. Interventions: None. Main Outcome Measures: Medical history, physical examination findings, laboratory measurements and prescribed therapies. Results: A total of 92 patients seen from 2014 to 2018 are described (age 15.9 years, range 11-24 years, body mass index 35.6 kg/m2, range 19.9-53.5). Metabolic syndrome features were common: 26% had a prediabetes hemoglobin A1c (>5.6%), 83% had a high-density lipoprotein (HDL) 120 mm Hg, and 43% had an alanine aminotransferase level of >30 U/L. Dermatologic findings included acne 93%, hirsutism 38%, acanthosis nigricans 85%, hidradenitis suppurativa 16%, and androgenic alopecia 2%. Of the patients, 33% had a diagnosis of depression or anxiety, 16% of patients had a diagnosis of obstructive sleep apnea, and an additional 59% had symptoms warranting a sleep study The most commonly prescribed medications were topical acne preparations (62%), followed by estrogen-containing hormonal therapy (56%) and metformin (40%). Conclusion: In adolescents with PCOS and obesity, metabolic, dermatologic, and psychologic co-morbidities are common. The use of a multidisciplinary clinic model including dermatology in addition to endocrinology, gynecology, psychology, and lifestyle experts provides care for most aspects of PCOS.

Purpose: Up to 1.8% of youth identify as transgender; many will be treated with a gonadotropin-releasing hormone agonist (GnRHa). The impact of GnRHa on insulin sensitivity and body composition in transgender youth is understudied. We aimed to evaluate differences in insulin sensitivity and body composition in transgender youth on GnRHa therapy compared with cisgender youth. Methods: Transgender participants were matched to cisgender participants on age, body mass index, and sex assigned at birth. Transgender males (n=9, ages 10.1–16.0 years) on GnRHa (mean±standard deviation duration of exposure: 20.9±19.8 months) were compared with cisgender females (n=14, ages 10.6–16.2). Transgender females (n=8, ages 12.6–16.1) on GnRHa (11.3±7 months) were compared with cisgender males (n=17, ages 12.5–15.5). Differences in insulin sensitivity (1/[fasting insulin], homeostatic model of insulin resistance [HOMA-IR]), glycemia (hemoglobin A1C [HbA1c], fasting glucose), and body composition (dual-energy X-ray absorptiometry) were evaluated using a mixed linear regression model. Results: Transgender males had lower 1/fasting insulin and higher HOMA-IR (p=0.031, p=0.01, respectively), fasting glucose (89±4 vs. 79±13 mg/dL, p=0.012), HbA1c (5.4±0.2 vs. 5.2±0.2%, p=0.039), and percent body fat (36±7 vs. 32±5%, p=0.042) than matched cisgender females. Transgender females had lower 1/fasting insulin and higher HOMA-IR (p=0.028, p=0.035), HbA1c (5.4±0.1% vs. 5.1±0.2%, p=0.007), percent body fat (31±9 vs. 24±10%, p=0.002), and lower percent lean mass (66±8 vs. 74±10%, p

Objective This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions. Methods Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child’s birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time. Results The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed “Resilient,” “Recovery,” “Chronic,” “Escalating,” and “Elevated Partial Recovery.” Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the “Resilient” class (67.6%). Conclusions This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories.

Objective Despite recommendations that clinics for children with a difference of sex development (DSD) should include peer support, information on how to provide this support is lacking. We utilized a mixed-methods program evaluation to evaluate family satisfaction with our clinic-based volunteers (who either have DSD themselves or are a parent of a child with DSD) and to understand the experience of these volunteers. Methods Parents (n=29) of a child with DSD completed an electronic survey. Interviews were conducted with three clinic volunteers. Results Most participants (72%) met with a clinic volunteer and majority (81%) rated their interaction as helpful. Most common topics discussed between parents and volunteers included: connecting to support groups (81%), their child's future (62%), and learning about their child's diagnosis (48%). Half of parents (48%) attended an after-clinic support group lunch, and 43% of these attendees rated the lunch session as helpful. Parents who attended a lunch liked the experience because they met other families with a child with a similar medical condition (100%), met volunteers with a similar medical condition (64%), and it helped them think more positively about their child's future (64%). Those who did not attend a lunch cited logistical reasons for not attending. Conclusions Incorporating clinic volunteers into a multidisciplinary DSD clinic is associated with high reported rates of satisfaction by families and volunteers.

Context Diabetes and cardiovascular diseases are common among men with Klinefelter syndrome (KS) and contribute to high morbidity and mortality. Objective To determine if cardiometabolic-related diagnoses are more prevalent among youth with KS than matched controls in a large population-based cohort. Methods Secondary data analysis of electronic health records from 6 pediatric institutions in the United States (PEDSnet). Patients included all youth with KS in the database (n = 1080) and 4497 youth without KS matched for sex, age (mean 13 years at last encounter), year of birth, race, ethnicity, insurance, site, and duration of care (mean 7 years). The main outcome measures were prevalence of 5 cardiometabolic-related outcomes: overweight/obesity, dyslipidemia, dysglycemia, hypertension, and liver dysfunction. Results The odds of overweight/obesity (OR 1.6; 95% CI 1.4-1.8), dyslipidemia (3.0; 2.2-3.9), and liver dysfunction (2.0; 1.6-2.5) were all higher in KS than in controls. Adjusting for covariates (obesity, testosterone treatment, and antipsychotic use) attenuated the effect of KS on these outcomes; however, boys with KS still had 45% greater odds of overweight/obesity (95% CI 1.2-1.7) and 70% greater odds of liver dysfunction (95% CI 1.3-2.2) than controls, and both dyslipidemia (1.6; 1.1-2.4) and dysglycemia (1.8; 1.1-3.2) were higher in KS but of borderline statistical significance when accounting for multiple comparisons. The odds of hypertension were not different between groups. Conclusion This large, population-based cohort of youth with KS had a higher odds of most cardiometabolic-related diagnoses than matched controls.

Limited data are available on changes in metabolic parameters in transgender youth on testosterone therapy in comparison with cisgender females. Data from 42 transgender males on testosterone therapy were retrospectively analyzed. Body mass index (BMI) and lipid profile changes were compared with BMI-matched females. There was a significant increase in BMI over time in the transgender males as compared with the cisgender females, and a decrease in high-density lipoprotein in the transgender males after starting testosterone therapy. Longitudinal prospective studies with cisgender controls are needed to better define effects of testosterone therapy in adolescents.

Summary Introduction Caregivers of female infants with congenital adrenal hyperplasia (CAH) often confront complex medical decision-making (e.g., early feminizing genitoplasty). Objective This study aimed to evaluate the relevant medical decisions and subsequent decisional regret of caregivers following their child's genitoplasty. Study design Caregivers (N = 55) were recruited from multidisciplinary treatment programs for participation in a longitudinal study. Qualitative data was collected at 6–12 months following feminizing genitoplasty to evaluate caregiver-reported decision points across their child's treatment. Quantitative exploratory analysis evaluated pre-operative predictors of subsequent decisional regret. Discussion When prompted about their decision-making and potential regret, most caregivers (n = 32, 80%) reported that their daughter's genital surgery was their primary medical decision. Specific themes regarding genital surgery included the timing and type of surgery. Most caregivers reported no decisional regret (62%), with 38% reporting some level of regret. Greater pre-operative illness uncertainty predicted heightened decisional regret at follow-up, p = .001. Conclusion Two-thirds of caregivers of female infants with CAH reported not regretting their decision-making. Nevertheless, over one-third of caregivers reported some level of regret, suggesting the need for improvements in shared decision-making processes. Many, but not all, families reported that this regret was related to surgical decision-making. Reducing caregiver illness uncertainty (e.g., providing clear information to families) may increase their satisfaction with decision-making. Further research is needed to determine how the evolving care practices surrounding early genitoplasty will impact families. Download : Download high-res image (307KB) Download : Download full-size image Summary Figure . Levels of Caregiver Decisional Regret measured by the Decisional Regret Scale. Note. Conventional categorical classification of scores was used: 0 = “no regret”, 1 to 25 = “mild regret,” 26 to 100 = “moderate to severe regret”.

Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had insufficient responses with a median GH peak of 3.7 ng/ml (range 1.1-8.6). Growth patterns revealed a drastic decline in length z-scores within the first year of life but then stabilized afterward. Five were treated with GH; one discontinued due to inconsolability. The other four participants continued on GH with improvement in linear growth velocity. Other endocrinopathies were identified in 7 of the 11 participants in this cohort. This study indicates that GH deficiency is associated with MCAP and that children with MCAP and hypoglycemia and/or postnatal growth failure should be evaluated for GH deficiency and other endocrinopathies.

Context As many as 1.8% of adolescents identify as transgender and many more seek care, yet the impact of gender-affirming hormone therapy (GAHT) on cardiometabolic health is unknown. Objective To determine insulin sensitivity and body composition among transgender females (TF) and males (TM) on estradiol or testosterone, compared with cisgender females (CF) and males (CM). Design Pilot, cross-sectional study conducted from 2016–2018. Setting Academic regional transgender referral center. Participants Transgender adolescents on either testosterone or estradiol for at least 3 months were recruited. Nineteen TM were matched to 19 CM and 42 CF on pubertal stage and body mass index (BMI). Eleven TF were matched to 23 CF and 13 TF to 24 CM on age and BMI. Main Outcome Measures 1/[fasting insulin] and body composition (dual-energy x-ray absorptiometry). Results Total body fat was lower in TM than CF mean ± SD: (29% ± 7% vs 33% ± 7%; P = 0.002) and higher than in CM (28% ± 7% vs 24% ± 9%; P = 0.047). TM had higher lean mass than CF (68% ± 7% vs 64% ± 7%, P = 0.002) and lower than CM (69% ± 7% vs 73% ± 8%; P = 0.029). Insulin sensitivity was not different between the groups. TF had lower body fat than CF (31% ± 7% vs 35% ± 8%; P = 0.033) and higher than CM (28% ± 6% vs 20% ± 10%; P = 0.001). TF had higher lean mass than CF (66% ± 6% vs 62% ± 7%; P = 0.032) and lower than CM (69% ± 5% vs 77% ± 9%; P = 0.001). TF were more insulin resistant than CM (0.078 ± 0.025 vs 0.142 ± 0.064 mL/μU; P = 0.011). Conclusions Transgender adolescents on GAHT have significant differences in body composition compared with cisgender controls, with a body composition intermediate between BMI-matched CMs and CFs. These changes in body composition may have consequences for the cardiometabolic health of transgender adolescents. ClinicalTrials.gov NCT02550431

Parents of children with Disorders of Sex Development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (M(age) = 32.55 years, SD = 5.08) and 41 fathers (M(age) = 35.53 years, SD = 6.78) of 53 infants (M(age) = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents’ psychosocial response to their child’s diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.

The WNT family of proteins is crucial in numerous developmental pathways and tissue homeostasis. WNT4, in particular, is uniquely implicated in the development of the female phenotype in the fetus, and in the maintenance of müllerian and reproductive tissues. WNT4 dysfunction or dysregulation can drive sex-reversal syndromes, highlighting the key role of WNT4 in sex determination. WNT4 is also critical in gynecologic pathologies later in life, including several cancers, uterine fibroids, endometriosis, and infertility. The role of WNT4 in normal decidualization, implantation, and gestation is being increasingly appreciated, while aberrant activation of WNT4 signaling is being linked both to gynecologic and breast cancers. Notably, single-nucleotide polymorphisms (SNPs) at the WNT4 gene locus are strongly associated with these pathologies and may functionally link estrogen and estrogen receptor signaling to upregulation and activation of WNT4 signaling. Importantly, in each of these developmental and disease states, WNT4 gene expression and downstream WNT4 signaling are regulated and executed by myriad tissue-specific pathways. Here, we review the roles of WNT4 in women’s health with a focus on sex development, and gynecologic and breast pathologies, and our understanding of how WNT4 signaling is controlled in these contexts. Defining WNT4 functions provides a unique opportunity to link sex-specific signaling pathways to women’s health and disease.

INTRODUCTION: Differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. A phenotype of severe genital atypia in patients raised as male is a relatively rare occurrence and standards for management are lacking. Decision making for early surgical planning in these rare cases includes, but is not limited to, degree of atypia, location of testes, and presence of Müllerian remnants. In this study we describe surgical approaches and short-term outcomes for masculinizing genitoplasty in moderate to severe genital atypia in young patients raised male, for whom parents opted for early surgery. METHODS: This NIH-sponsored study is an ongoing, observational, multicenter investigation assessing medical, surgical and psychological outcomes in children and their parents affected by atypical genitalia due to DSD. Participants were prospectively enrolled from 12 children’s hospitals across the United States that specialize in DSD care. Criteria for child enrollment were a Quigley score of 3–6 in those with a 46, XY or 45,X/46, XY chromosome complement, age

Introduction Individuals who identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ) face significant health disparities and barriers to accessing care. Patients have reported provider lack of knowledge as one of the key barriers to culturally responsive, clinically competent care. Many US and Canadian medical schools still offer few curricular hours dedicated to LGBTQ-related topics, and medical students continue to feel unprepared to care for LGBTQ patients. Methods We developed a 10-hour LGBTQ health curriculum for preclinical medical and physician assistant students. The curriculum included lectures and case-based small-group discussions covering LGBTQ terminology, inclusive sexual history taking, primary care and health maintenance, and transition-related care. It also included a panel discussion with LGBTQ community members and a small-group practice session with standardized patients. Students were surveyed before and after completing the curriculum to assess for increases in confidence and knowledge related to LGBTQ-specific care. Results Forty first- and second-year medical students completed the sessions and provided valid responses on pre- and postcourse surveys. Nearly all students initially felt unprepared to sensitively elicit information, summarize special health needs and primary care recommendations, and identify community resources for LGBTQ individuals. There was significant improvement in students' confidence in meeting these objectives after completion of the five sessions. Knowledge of LGBTQ health issues increased minimally, but there was a significant increase in knowledge of LGBTQ-related terminology. Discussion Our 10-hour LGBTQ health curriculum was effective at improving medical students' self-confidence in working with LGBTQ patients but was less effective at increasing LGBTQ-related medical knowledge.

Individuals mosaic for monosomy X and a cell line with Y chromosome material can have genitalia that appear phenotypical female, male, or ambiguous. Those with this karyotype and typical female genitalia are diagnosed with Turner syndrome; however, this definition specifically excludes those with genitalia other than typical female. There is limited information on whether medical and neurodevelopmental risks are similar among individuals with monosomy X and Y chromosome material across genital phenotypes. This multicenter retrospective study compared comorbidities and clinical management in individuals with monosomy X and Y material and male/ambiguous genitalia to those with typical female genitalia. Electronic medical records for all patients with monosomy X and Y material (n = 76) at two large U.S. pediatric centers were abstracted for predetermined data and outcomes. Logistic regression was used to compare the two phenotypic groups adjusting for site and duration of follow-up. The male/ambiguous genitalia group was just as likely to have congenital heart disease (RR 1.0, 95%CI [0.5-1.9]), autoimmune disease (RR 0.6 [0.2-1.3]), and neurodevelopmental disorders (RR 1.4 [0.8-1.2]) as those with female genitalia. Despite similar risks, they were less likely to receive screening and counseling. In conclusion, individuals with monosomy X and Y chromosome material have similar medical and neurodevelopmental risks relative to individuals with Turner syndrome regardless of genitalia, but there are notable differences in clinical management.

Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events.

Summary Introduction Differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. A phenotype of severe genital atypia in patients raised as male is a relatively rare occurrence and standards for management are lacking. Decision making for early surgical planning in these rare cases includes, but is not limited to, degree of atypia, location of testes, and presence of Mϋllerian remnants. In this study we describe surgical approaches and short-term outcomes for masculinizing genitoplasty in moderate to severe genital atypia in young patients raised male, for whom parents opted for early surgery. Methods This NIH-sponsored study is an ongoing, observational, multicenter investigation assessing medical, surgical and psychological outcomes in children and their parents affected by atypical genitalia due to DSD. Participants were prospectively enrolled from 12 children's hospitals across the United States that specialize in DSD care. Criteria for child enrollment were a Quigley score of 3–6 in those with a 46, XY or 45,X/46, XY chromosome complement, age Results Of the 31 participants, 30 underwent hypospadias repair and 1 patient did not undergo a genitoplasty procedure. The majority of participants (22) received a staged hypospadias repair. Seventeen complications were identified in 12 of the 31 children (41%) at 12 months of follow up. Glans dehiscence and urethrocutaneous fistula were the most common complications. Orchiopexy was performed in 14 (44%) and streak gonads were removed in 4 (13%) participants. Both parents and surgeons reported improved cosmesis after surgery when compared to baseline. Conclusion Genitoplasty was chosen by parents for the majority of children eligible for study. No single surgical approach for masculinizing moderate to severe genital ambiguity in young patients with 46, XY or 45,X/46, XY DSD was adopted by all surgeons. Complications occurred in 41% of those who underwent genitoplasty for severe hypospadias. Overall, appearance of the genitals, as determined by parents and surgeons, improved following genitoplasty. Outcomes of early genitoplasty are needed to guide families when making decisions about such procedures for their young children. Download : Download high-res image (286KB) Download : Download full-size image Summary Figure . River plot comparing Likert cosmesis score over time for mothers, fathers, and surgeons. Panel A includes all patients in the cohort.

Objective A subset of parents of children with disorders/differences of sex development (DSD) including ambiguous genitalia experience clinically elevated levels of anxious and depressive symptoms. Research indicates that uncertainty about their child’s DSD is associated with parent psychosocial distress; however, previous studies have been cross-sectional or correlational in nature. The current study is the first to examine the longitudinal trajectory of the relationship between caregiver-perceived uncertainty about their child’s DSD and caregiver anxious and depressive symptoms across the first 12 months following genital surgery in young children, or if surgery was not performed, the first 12 months following study entry. Methods One hundred and thirteen caregivers (Mage = 32.12; 57.5% mothers; 72.6% Caucasian) of children (N = 70; Mage = 9.81 months; 65.7% female) with DSD were recruited from 12 DSD specialty clinics in the United States. Caregivers completed psychosocial measures at baseline, 6 and 12 months following genitoplasty, or study entry if parents elected not to have surgery for their child. Results Caregiver illness uncertainty and both anxious and depressive symptoms were highest at baseline and decreased over time (ps < .05). Caregiver illness uncertainty predicted symptoms of anxious and depressive symptoms across all time points (ps < .05). Conclusions Caregivers’ perceptions of uncertainty about their child’s DSD are highest soon after diagnosis, and uncertainty continues to predict both anxious and depressive symptoms across time. Thus, the initial diagnostic period is a critical time for psychological assessment and intervention, with parent illness uncertainty being an important clinical target.

Objective Poor sleep is common among adolescents and associated with impaired mood and health-related quality of life (HRQOL). Transgender individuals are at increased risk of mood problems hypothesized to be due to minority stress; however, no research has investigated associations between sleep and mood in this population. We aimed to examine sleep, mood, and HRQOL in transgender adolescent males. Design & setting Transgender males age 13-16 were recruited from a U.S. gender diversity clinic. Measurements Participants completed one week of home actigraphy monitoring. Questionnaires assessed insomnia symptoms, chronotype, mood, and HRQOL. Pearson correlations between sleep, mood, and HRQOL were examined. Results A total of 10 participants completed study measures during the school year. Participants obtained less than the recommended 8-10 hours of sleep per night, and half of participants endorsed insomnia symptoms. Greater insomnia symptoms were correlated with higher anxiety (P = .04) and depression (P = .04) symptoms, and poorer Psychosocial HRQOL (P = .03). Earlier weekday and weekend bed and wake times and earlier weekday sleep midpoint were associated with better Wellbeing HRQOL. No other significant correlations between sleep and mood or HRQOL variables were found. Conclusions Anxiety and depression symptoms were associated with self-reported insomnia symptoms, while HRQOL was associated with both insomnia symptoms and objective sleep timing in this sample of adolescent transgender males. Clinicians should assess both sleep and mood symptoms in this population and future research should evaluate the impact of improved sleep and gender-affirming care on mood and HRQOL for transgender adolescents.

Mentorship is a critical component of career development, particularly in academic medicine. Peer mentorship, which does not adhere to traditional hierarchies, is perhaps more accessible for underrepresented groups, including women and minorities. In this article, we review various models of peer mentorship, highlighting their respective advantages and disadvantages. Structured peer mentorship groups exist in different settings, such as those created under the auspices of formal career development programs, part of training grant programs, or through professional societies. Social media has further enabled the establishment of informal peer mentorship through participatory online groups, blogs, and forums that provide platforms for peer-to-peer advice and support. Such groups can evolve rapidly to address changing conditions, as demonstrated by physician listserv and Facebook groups related to the COVID-19 pandemic. Peer mentorship can also be found among colleagues brought together through a common location, interest, or goal, and typically these relationships are informal and fluid. Finally, we highlight here our experience with intentional formation of a small peer mentoring group that provides structure and a safe space for professional and social-emotional growth and support. In order to maximize impact and functionality, this model of peer mentorship requires commitment among peers and a more formalized process than many other peer mentoring models, accounting for group dynamics and the unique needs of members. When done successfully, the depth of these mentoring relationships can produce myriad benefits for individuals with careers in academic medicine including, but not limited to, those from underrepresented backgrounds.

OBJECTIVE To assess the odds of a psychiatric or neurodevelopmental diagnosis among youth with a diagnosis of gender dysphoria compared with matched controls in a large electronic health record dataset from 6 pediatric health systems, PEDSnet. We hypothesized that youth with gender dysphoria would have higher odds of having psychiatric and neurodevelopmental diagnoses than controls. STUDY DESIGN All youth with a diagnosis of gender dysphoria (n = 4173 age at last visit 16.2 ± 3.4) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables to controls without gender dysphoria (n = 16 648, age at last visit 16.2 ± 4.8) using multivariable logistic regression. The odds of having psychiatric and neurodevelopmental diagnoses were examined using generalized estimating equations. RESULTS Youth with gender dysphoria had higher odds of psychiatric (OR 4.0 [95% CI 3.8, 4.3] P

Purpose Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States. Methods Eligible participants had moderate-to-severe genital atypia, were aged

Context Little is known about the health of transgender adults in the United States, a growing population. There have been no large reports examining differences in health status and cardiometabolic disease in subgroups of transgender adults [female-to-male (FTM), male-to-female (MTF), and gender nonconforming (GNC)] in the United States. Objective Compare the health status and prevalence of cardiometabolic disease among specific subgroups of transgender adults (FTM, MTF, GNC) with those of cisgender adults in the United States. Design Secondary data analysis based on the 2015 Behavioral Risk Factor Surveillance System survey. Setting The 22 states in the United States that asked about transgender identity. Participants Noninstitutionalized adults age ≥18 years who reside in the United States, identified through telephone-based methods. Main Outcome Measures Data were extracted for respondents who answered the transgender identity question. Weighted percentages are given for all measures. Adjusted odds ratios (ORs) are reported for health status and cardiometabolic disease measures. Results FTM adults have a higher odds of being uninsured than both cisgender women [OR 3.8; 95% confidence interval (CI), 2.1 to 7.1] and cisgender men (OR 2.5; 95% CI, 1.4 to 4.7). MTF adults have a higher odds of reporting myocardial infarction than cisgender women (OR 2.9; 95% CI, 1.6 to 5.3) but not cisgender men. Conclusions There are significant differences in health status measures and cardiometabolic health between subgroups of transgender adults and cisgender adults. There is a need for additional research to understand the societal and medical (e.g., hormone therapy) effects on these outcomes., There are differences in health status and cardiometabolic health among subgroups of transgender adults compared with cisgender adults on the 2015 Behavioral Risk Factor Surveillance System survey.

Background: Studies of transgender adults on gender affirming hormone therapy have shown increased rates of cardiovascular events (myocardial infarction and stroke) and features of metabolic syndrome including increased body mass index (BMI, transgender males) and dyslipidemia (transgender males and females). Studies in youth are limited by mostly small, single-center studies. With 1.8% of adolescents identifying as transgender, and increasing referral rates to gender clinics for care, more information is needed to better inform clinicians, patients and families about potential health risks in this cohort. PEDSnet, a pediatric Learning Health System, captures data from some of the largest pediatric care institutions in the U.S. We aimed to evaluate differences in diagnoses related to metabolic syndrome or cardiometabolic risk among youth with a diagnosis of gender dysphoria compared to matched cisgender controls. Methods: All youth with a diagnosis of gender dysphoria (n=4,177) and at least one outpatient encounter were extracted from the PEDSnet database (6 sites, years 2009-2019) and propensity-score matched on 7 variables (year of birth, age at last visit, site, race, ethnicity, insurance status, duration in database) to 4 controls without gender dysphoria (n=16,664). The odds of having a diagnosis of overweight/obesity, hypertension, dyslipidemia, dysglycemia, liver dysfunction, polycystic ovary syndrome (PCOS) or metabolic syndrome, was examined using generalized estimating equations with an interaction term for sex (as listed in the chart). Results: Of the transgender youth, 66% were female sex, 73% were white race, 9% were of Hispanic ethnicity, and 61% had private insurance. The control group was similar: 67% female sex, 72% white, 9% Hispanic, and 61% had private insurance. Transgender youth and controls both had on average 7 years duration in the database and were 16.2 years old at last visit. Transgender youth had higher odds of dyslipidemia (OR: 1.6 [95% CI: 1.3, 1.8], p

Background: While cardiac complications, short stature, and infertility are often discussed in the context of Turner Syndrome (TS), abnormalities of liver function are less well described. In order to address this gap in knowledge, we sought to better characterize hepatic abnormalities in youth with TS. Methods: PEDSnet is a collaboration across 7 major US pediatric institutions that unifies electronic medical data including diagnoses, prescriptions, and laboratory measurements for over 6 million children. 2,145 females with a diagnosis of TS were matched to 8,580 females without TS (1:4 ratio) on site, race (68% White), ethnicity (15% Hispanic), payer source, year of birth, age at most recent visit (median 14 years), and duration of care (mean 8 years). Outcomes of interest included highest recorded liver enzyme values (AST and ALT) categorized as normal or above the upper limit of normal (ULN) defined as >95th percentile for their age, and specific liver diagnoses. Proportions were compared between the cohorts using odds ratios (OR) and 95% confidence intervals (CI) from a generalized estimating equations approach. Multinomial logistic regression was conducted to investigate potential risk factors for liver abnormalities within the TS cohort. Results: Out of 1,159 girls with TS who had liver enzymes recorded in PEDSnet, 58% had at least one AST or ALT above the ULN. TS patients were more likely to have enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), more likely to be in the 2-3 times ULN category (OR: 2.7, 95% CI: 1.7-3.3), and more likely to be in the >3 times ULN category (OR: 1.7, 95% CI: 1.3-2.2) compared to girls without TS. TS patients were also more likely to have any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), including significantly higher risk of fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0), and liver tumor/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In the multinomial model, age, BMI, and the presence of a thyroid condition, cardiovascular diagnosis, or diabetes significantly (p < 0.05) increased the risk for elevated liver enzymes in girls with TS, while mosaicism, estrogen prescription, and celiac disease did not. Stratifying by age groups, over 40% of girls with TS had ALT elevations (24% > 2 times ULN, some with diagnosed liver conditions) under age 10, when liver screening is officially recommended per TS guidelines. Conclusions: Prevalence of elevated liver enzymes and diagnoses of liver disease are significantly higher in youth with TS vs. controls, emphasizing the need for clinical monitoring and additional research. Given the high percentage of girls

OBJECTIVE: To evaluate the odds of a behavioral health diagnosis among youth with a difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) compared with matched controls in the PEDSnet database. STUDY DESIGN: All youth with a diagnosis of DSD (n=1,216) or CAH (n=1,647) and at least one outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables (1:4) to controls (n=4,864 and 6,588, respectively) using multivariable logistic regression. The likelihood of having behavioral health diagnoses was examined using generalized estimating equations. RESULTS: Youth with a DSD had higher odds of a behavioral health diagnosis (OR: 1.7 [95% CI: 1.4, 2.1], p

Background Menstrual bleeding can worsen gender dysphoria in transgender males. Gender affirming hormone therapy with testosterone has been shown to induce amenorrhea in the majority of adult patients within 6 months. Little is known about the effects of testosterone with adjunctive menstrual suppression agents in adolescents and young adults. The objective of our study was to describe time to cessation of menses in transgender males with testosterone and/or other hormonal therapies. Methods An IRB-approved chart review was performed on patients with a female sex assigned at birth ages 10-24 with ICD-10 codes for gender dysphoria started on hormonal therapy from January 1, 2013 to January 1, 2019. Primary outcome was time to cessation of menses. Deidentified demographic, clinical, and prescription data was abstracted. IBM SPSS v 27 was used to compute descriptive statistics and Kaplan-Meier survival to estimate median time to amenorrhea. Results 256 patients were included in the study and the mean age was 15.8 (±1.9) years. The majority (95.7%) identified as transgender male or transmasculine. Almost half of patients (46.5%) reported monthly periods and 16.4 % had irregular periods. Patients that were amenorrheic (12.1%) or who received no treatment (2.0%) were excluded from further analysis. In the remaining 220 patients, the median time to cessation of menses was 182 days. 140 (63.6%) patients started testosterone without prior menstrual management. For those patients treated with testosterone alone (n = 105), the median time to cessation of menses was 151 days. Patients started on testosterone with norethindrone acetate (n=5) had a median time to amenorrhea of 188 days compared to 168 days for those starting on testosterone and depot medroxyprogesterone acetate (DMPA, n=15). 18 patients were started on a progestin therapy after initiation of testosterone to induce menstrual suppression. The median time to amenorrhea from addition of DMPA (n=4) was 168 days compared to 56 days when norethindrone acetate was added (n=11). See Table 1 and Figure 1. For the remaining 36.4% (n = 80) of patients, considerable variability in prescribing patterns was noted. Conclusions The majority of patients starting testosterone for gender dysphoria have menstrual bleeding. Unlike adult studies, less than half of patients starting testosterone achieve amenorrhea within 6 months. For patients not satisfied with menstrual control, there appears to be a wide variety of practice patterns, with some suggestion that norethindrone acetate may achieve amenorrhea quicker than DMPA. Prospective studies are needed to determine if this difference is significant and provide guidance to providers on the optimal hormonal regimen.

Background/Aims: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child’s DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency). Methods: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling. Results: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction. Conclusion: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety.

ContextUp to 1.8% of adolescents identify as transgender and many more seek care, yet the impact of gender affirming hormone therapy (GAHT) on cardiometabolic health is unknown.ObjectiveTo determine insulin sensitivity and body composition among transgender females (TF) and males (TM) on estradiol or testosterone, compared to cisgender females (CF) and males (CM).DesignPilot, cross-sectional study conducted from 2016-2018.Setting. Academic regional transgender referral center.ParticipantsTransgender adolescents on either testosterone or estradiol for at least 3 months were recruited. Nineteen TM were matched to 19 CM and 42 CF on pubertal stage and body mass index (BMI). Eleven TF were matched to 23 CF and 13 TF to 24 CM on age and BMI.Main Outcome Measure(s)1/[fasting insulin] and body composition (dual-energy absorptiometry, DXA).ResultsTotal body fat was lower in TM than CF (29±7 vs. 33±7%, p=0.002) and higher than CM (28±7 vs. 24±9%, p=0.047). TM had higher lean mass than CF (68±7 vs. 64±7%, p=0.002) and lower than CM (69± vs. 73±8%, p=0.029). Insulin sensitivity was not different between the groups.TF had lower body fat than CF (31±7 vs. 35±8%, p=0.033) and higher than CM (28±6 vs. 20±10, p=0.001). TF had higher lean mass than CF (66±6 vs. 62±7%, p=0.032) and lower than CM (69±5 vs. 77±9%, p=0.001). TF were more insulin resistant than CM (0.078±0.025 vs. 0.142±0.064, p=0.011).ConclusionsTransgender adolescents on GAHT have significant differences in body composition compared to cisgender controls, with a body composition intermediate between BMI-matched cisgender males and females. These changes in body composition may have consequences for the cardiometabolic health of transgender adolescents.PrecisTransgender youth on gender affirming hormone therapy have differences in their percent fat and lean mass compared to cisgender (non-transgender) youth.

Background and Objectives: Among youth, 0.7% identify as transgender. Markers of cardiometabolic health and body composition in transgender youth undergoing gender-affirming hormone therapy have not been rigorously studied. Our objectives were to evaluate differences in body composition, insulin sensitivity, lipid profile, and aspartate and alanine aminotransferases (AST, ALT) in male-to-female (MTF) youth treated with estradiol (E2) compared to non-transgender female (FC) and male controls (MC). Methods: Fourteen MTF E2-treated (mean + SD E2 dose 1.5 + 1.0 mg/day, duration 1 + 0.8 years) participants (aged 14.5-19.4 years) were compared to BMI percentile-category-matched and age-matched (within 1 year) FC (n=23, aged 14.2-18.3) and MC (n=24, aged 14.5-19.8). Three MTF participants were also on a gonadotropin releasing-hormone analogue (GnRHa) for suppression of endogenous testicular function. Participants had fasted morning laboratory testing and body composition measured by dual-energy X-ray absorptiometry (DXA). Differences (mean + SD) in body composition, insulin sensitivity (estimated from 1/[fasting insulin]), lipids, leptin, AST, ALT and blood pressure (BP) were evaluated using a mixed linear regression model with a random effect for the matched set. A spearman correlation was performed to evaluate for a correlation between 1/[fasting insulin] and % lean mass. Results: MTF vs. FC: Total testosterone was higher in MTF vs. FC (224 + 182 vs. 43 + 10 ng/dL, respectively, p

Children and adolescents with gender dysphoria are presenting for medical attention at increasing rates. Standards of Care have been developed which outline appropriate mental health support and hormonal interventions for transgender youth. This article defines terminology related to gender identity, reviews the history of medical interventions for transgender persons, outlines what is known about gender identity development, and reviews mental health disparities faced by this patient population. We provide an overview of medical management options for transgender adolescents meeting diagnostic criteria for gender dysphoria including pubertal suppression, cross-sex hormones, longitudinal screening and anticipatory guidance. We describe current challenges in the field and provide information about how care is currently being provided in the US and Canada. We conclude with 5 brief case examples.

Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. There are 3 reports of individuals with a dominantly acting heterozygous variant leading to a clinically significant phenotype. We report a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens. He was found to have a de novo heterozygous novel variant in STAR: c.65-2A>C. We report a case of a novel variant and review of other dominant mutations at the same position in the literature. Clinicians should be aware of the possibility of attenuated genital phenotypes of LCAH and the contribution of de novo variants in STAR at c.65-2 to the pathogenesis of that phenotype.

Context: Obesity is known to impact reproductive function in adults, but little is known about its effects on reproductive hormones during puberty or sex differences in these effects. Objective: To assess sex differences in effects of obesity on reproductive hormones and their relationship to insulin sensitivity and secretion. Design: Cross-sectional study including anthropometrics, serum and urine reproductive hormone concentrations, and intravenous glucose tolerance testing (IVGTT) to assess acute insulin response to glucose (AIRg) and insulin sensitivity (Si). Setting: Outpatient academic clinical research center. Patients: Fifty-one normal weight (NW, BMI-Z=-0.11 +/- 0.77, age=11.5 +/- 1.7 years) and 53 obese (BMI-Z=2.22 +/- 0.33, age=10.9 +/- 1.5 years) girls (n=54) and boys (n=50), Tanner stage 2-3. Results: Obese boys had lower total testosterone (p

Androgen insensitivity syndrome (AIS) is caused by mutations in the gene encoding the androgen receptor (AR). The incidence of AIS is estimated to be 1 in 99,000. Complete androgen insensitivity syndrome (CAIS) is characterized by a 46,XY karyotype with external genitalia that appear typically female and results from mutations that render the androgen receptor non-functional. Partial androgen insensitivity syndrome (PAIS) results from partial loss of function mutations in AR. Rarely, PAIS results from somatic mosaicism for an AR mutation and not from a hypomorphic variant. We present two cases of PAIS due to somatic mosaicism, one caused by a novel nonsense mutation and one caused by a missense mutation previously reported in CAIS. Two patients with atypical genitalia presented to our multidisciplinary clinic for disorders of sex development and sequencing of AR was performed as part of the diagnostic evaluation. In case one, AR sequencing revealed mosaicism for a nonsense mutation, c.1331T > A; p.Leu444Ter. This mutation has not previously been reported, but is presumed to be pathogenic. In case two, AR sequencing revealed a mosaic missense mutation, c.2279 C > A; p.Ser760Tyr, which has previously been reported in CAIS but not in PAIS. Similar phenotypes may result from AR mutations that are present in a mosaic state with full loss of function or hypomorphic mutations that partially impair the function of the protein in either all tissues or in a mosaic state.

Summary Introduction Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. Objective The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. Study design This 11-site, prospective study included children aged ≤2 years, with Prader 3–5 or Quigley 3–6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. Results Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) ( Summary Figure ). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. Discussion In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. Conclusion In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management. Download : Download high-res image (236KB) Download : Download full-size image Summary Figure . Surgical complications at 12-month postoperative follow-up, n = 27. *Among the six complications in the masculinizing surgery group, one patient developed both urinary retention (minor) and urethrocutaneous fistula (major). ǂAmong the five complications in the feminizing surgery group, one patient had both a mucosal skin tag (minor) and vaginal mucosal polyp (minor).