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The impact of parent-reported stigma due to their child's disorder/difference of sex development (DSD) on parent psychosocial adjustment is poorly understood. In other pediatric populations, perceived interference of medical conditions into daily activities (i.e., illness intrusiveness ) mediates the relationship of stigma to adjustment. This study assessed relationships between parent-focused and child-focused stigma → illness intrusiveness → depressive and anxious symptoms . Exploratory analyses sought to identify patient characteristics associated with stigma.Caregivers (59 women and 43 men) of 63 children diagnosed with a DSD up to age 4 years completed measures of demographics, parent-focused and child-focused stigma, illness intrusiveness, and depressive and anxious symptoms.Increased parent-focused and child-focused stigma were associated with increased illness intrusiveness, which, in turn, was associated with increased depressive and anxious symptoms for parents nested within dyads. Among children with DSD family histories, parents reported greater child-focused stigma.Parents who experience DSD-related stigma report greater interference of their child's DSD into their daily activities, which is associated with poorer psychosocial adjustment. Findings support developing clinical interventions related to parents' perceptions of stigma and illness intrusiveness to improve parent adjustment.

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.

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.

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.

Background: Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. Aims: This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. Methods: A survey was performed among health care professionals who use the International DSD Registry (I-DSD). Results: Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. Conclusion: Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.

Purpose Provide recommendations for the development of an interdisciplinary care (IDC) clinic for the treatment of youth with disorders/differences of sex development (DSD). DSD consist of a group of complex congenital medical disorders in which the development of chromosomal, gonadal, or anatomical sex is atypical. Youth with DSD require care from multiple specialized healthcare disciplines, including several medical specialties, surgery, nursing, and mental health. Method Recommendations are based on an interdisciplinary care clinic model that allows for a team of relevant professionals who share knowledge, ideas, and responsibility of care. The framework established in this article is based largely on experiences at an established DSD clinic, as well as observations of multiple clinics across the United States. Results Preliminary outcome data on clinic adherence to treatment protocol under an IDC model are provided. Conclusions To meet the diverse healthcare needs of youth with DSD, comprehensive care clinics are recommended; however, few such clinics exist in the United States. Establishing new comprehensive DSD clinics can be challenging due to the highly unique treatment of DSD, but the current paper expands the literature available to guide clinic development in the United States.

Purpose of review The review focuses on genitoplasty, performed on young children with disorders/differences of sex development (DSD) to 'typify' ambiguous external genitalia and intended to result in either male or female-appearing genitals. Consensus on whether or not early genitoplasty is optimal or appropriate has yet to be achieved. This article reviews arguments in favor of early surgery as well as those disputing their justification. Recent findings Arguments supporting early genitoplasty include the assumption that a child's genital anatomy should match their gender of rearing for optimal psychosocial development and that outcomes are better physically and psychologically than when surgery is deferred. Those disputing their justification argue that they deny patients the right to participate in irreversible decisions related to anatomy and gender, revoke the possibility of an open future, and violate basic human rights. Clinical management includes recommendations for interdisciplinary care integrating psychologists, and shared decision-making processes to assist families in carefully considering options. Summary Early genital surgery in DSD care is controversial with compelling arguments put forth by both proponents and opponents. Relevant issues can be examined from ethical, psychological, cultural and medical perspectives - all of which need to be accounted for in both research and standard of care development.

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).

PURPOSE: We examined the psychological adjustment of parents of children born with moderate to severe genital atypia 12 months after their child underwent genitoplasty. MATERIALS AND METHODS: Parents were recruited longitudinally from a multicenter collaboration of 10 pediatric hospitals with specialty care for children with disorders/differences of sex development and/or congenital adrenal hyperplasia. Parents completed measures of depressive and anxious symptoms, illness uncertainty, quality of life, posttraumatic stress and decisional regret. RESULTS: Compared to levels of distress at baseline (before genitoplasty) and 6 months after genitoplasty, data from 25 mothers and 20 fathers indicated significant improvements in all psychological distress variables. However, a subset of parents continued endorsing clinically relevant distress. Some level of decisional regret was endorsed by 28% of parents, although the specific decision that caused regret was not specified. CONCLUSIONS: Overall the majority of parents were coping well 1 year after their child underwent genitoplasty. Level of decisional regret was related to having a bachelor’s level of education, increased levels of illness uncertainty preoperatively and persistent illness uncertainty at 12 months after genitoplasty but was unrelated to postoperative complications.

Disorders/differences of sex development (DSD) comprise multiple congenital conditions in which chromosomal, gonadal, and/or anatomical sex are discordant. The prediction of future gender identity (i.e., self-identifying as male, female, or other) in children with DSD can be imprecise, and current knowledge about the development of gender identity in people with, and without DSD, is limited. However, sex of rearing is the strongest predictor of gender identity for the majority of individuals with various DSD conditions. When making decisions regarding sex of rearing biological factors (e.g., possession of a Y chromosome, degree and duration of pre- and postnatal androgen exposure, phenotypic presentation of the external genitalia, and fertility potential), social and cultural factors, as well as quality of life should be considered. Information on gender identity outcomes across a range of DSD diagnoses is presented to aid in sex of rearing assignment.

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) – (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46, XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) – the male-typical pattern – than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD.

Objective Caregivers of children with a disorder of sex development (DSD) are at increased risk for maladaptive parenting capacities, such as high levels of parental overprotection and perceived vulnerability of their child, in addition to parenting stress. The current study aims to examine whether there are relationships between these parenting capacities and psychological distress, including depressive and anxious symptoms. Patients and methods Participants included 134 caregivers of 90 children with a DSD. Caregivers completed measures of parental overprotection, perceived vulnerability, parenting stress, anxiety, and depression. Results Hierarchical regression analyses revealed that higher levels of parenting stress were related to more anxious and depressive symptoms in caregivers. Higher levels of perceived vulnerability were related to more anxious symptoms. Levels of parental overprotection were unrelated to anxious or depressive symptoms. Conclusions There is a relationship between parenting capacities and mental health outcomes in caregivers of children with DSD, although the direction of this relationship is not clear. Given the strong relationships between parenting stress and anxious and depressive symptoms, targeting parenting stress and/or psychological distress in these caregivers could result in better functioning overall.

Summary Background The birth of a child with a disorder of sex development (DSD) and atypical genitalia can be traumatizing and isolating for families. Parents of children with DSD are at risk for increased levels of psychological distress, including depression, anxiety, illness uncertainty (IU), post-traumatic stress symptoms (PTSS), and impairments in quality of life (QOL). Our previous report indicated that although the majority of parents of children with atypical genitalia were coping well prior to the child's genitoplasty, approximately 25% of them reported experiencing some type of psychological distress. Objective The current study sought to examine the trajectory of parental psychological distress prior to, and 6 months after their child underwent genitoplasty. Methods Parents were recruited as part of an ongoing, prospective, multi-site study involving 10 pediatric hospitals with specialized care for children with atypical genitalia. Results from 49 parents (27 mothers, 22 fathers) of 28 children (17 female sex of rearing, 11 male sex of rearing) born with atypical genitalia (Prader rating of 3–5 in 46,XX DSD or by a Quigley rating of 3–6 in 46,XY DSD or 45,XO/46,XY) were included in the study. Results There were no significant changes in level of depressive or anxious symptoms or quality of life between baseline and 6-month post-operative follow-up, although mothers continued to report significantly higher levels of depressive symptoms than fathers, and as a group, these parents reported lower QOL than published norms. The level of PTSS significantly decreased for all parents, suggesting that parents may have come through the acute stress phase associated with their child's diagnosis. Finally, while there were no significant changes in IU over the time period, the level of IU for parents of boys actually increased, while parents of girls reported no change (Figure). Conclusion Six months after their child has undergone genitoplasty, the majority of parents report minimal levels of psychological distress. However, a subset of these parents continue to experience significant distress related to their child's diagnosis. Specifically, parents of boys appear to be at increased risk for difficulties, which may be related to either the lack of clinical diagnosis for almost half of these children or the necessity of two-stage surgeries for the majority of them. We will continue collecting data on these families to better understand the trajectory of these adjustment variables. Download : Download high-res image (173KB) Download : Download full-size image Figure . Graphs of significant changes.

BACKGROUND: Hypogonadism is common with opiate-like drug use and may contribute to cognitive abnormalities. With the increasing epidemic of HIV and substance use (SU) worldwide, it is important to understand the impact of these conditions on cognition, which may affect quality of life and possibly decrease adherence to treatment. We hypothesized that men with SU, by virtue of hypogonadism secondary to HIV and/or SU, may demonstrate impaired cognition. METHODS: We recruited men aged 18-50 from a population of low income, inner-city individuals. Details of HIV and SU status, serum blood levels of total testosterone (TT), free testosterone (FT) and estradiol (E2) were assessed. All subjects were administered ten neuropsychological tests. RESULTS: Our sample consisted of 68 men (mean age: 43.2 years (SD 5.8), African Americans: 86.6%). The recruited population was primarily from low socioeconomic status and unemployed. The mean level of TT was 553.9ng/dL (SD 262.0), the mean level of FT was 69.5pg/mL (SD 34.8), mean E2 was 3.2pg/mL (SD 4.4). We found that 30.9% were hypogonadal and it was associated with higher SU. We observed some relationships between sex hormones and cognitive domains, however, after adjustment for age, drug use category, education, depression, HIV, there was no statistically significant correlation between cognitive performance and sex hormone levels. CONCLUSIONS: In this cross-sectional study of men with a high prevalence of SU and hypogonadism, endogenous levels of TT, FT or E2 were not related to cognitive performance. Other factors need to be identified which may contribute to poor cognitive function in the setting of SU. Language: en

Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center.The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery.This prospective, observational study included children aged2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty.Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings.This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life.In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.

Rearing a child with a chronic illness is stressful and can potentially affect parenting style, which may result in poorer outcomes for children. The purpose of this study was to compare parenting characteristics of female caregivers rearing children with a disorder of sex development (DSD) to female caregivers rearing children with type 1 diabetes mellitus (T1DM). Caregivers of both groups were matched according to age and compared on measures of stress and parenting practices. Both groups demonstrated significant levels of stress and negative parenting practices. Children with T1DM and male children with non-life-threatening DSD were perceived as more vulnerable by their caregivers. Better understanding of parenting experiences of female caregivers rearing children with DSD, particularly male children, will facilitate the development of individualized interventions to ameliorate negative parenting practices and stress, with the long-term goal of improved health outcomes for their children.

Early development of the percentage of fat and muscle is rarely considered, but is important because excessive fat is related to the development of diabetes and other morbidities later in life. In pediatric medicine, there are few to no data comparing sex differences in body composition in the first months of life despite the fact that males are typically longer and weigh more than girls at birth.The purpose of this study was to determine whether observed sex differences in body composition at birth persist through the first 6 months of life.Participants were healthy, full-term, male and female newborns. Children throughout the Oklahoma City, Oklahoma, metropolitan area were enrolled. The inclusion criteria were: mothers aged 18 to 45 years at the time of delivery; a term pregnancy lastingor=37 weeks of gestation (determined by mother's physician); weight adequate for gestational age; and a hospital stay for the infant of3 days following delivery. The exclusion criteria were: maternal tobacco use or alcohol consumption (1 drink per week) during pregnancy; gestational diabetes; preeclampsia; and infants with presumed or known congenital birth defects. Baseline assessment at birth included length and weight. Newborns had their body composition (percent fat [%fat], total fat, and fat-free mass) determined at approximately 1 month of age using whole body plethysmography. Mothers were invited to have their children take part in a 5-month extension that conducted additional body composition measurements at 3 and 6 months of age.Sixty-four girls (mean [SD] age at time of testing, 20.9 [7.9] days; birth weight, 3500 [388] g; birth length, 49.9 [2.4] cm; white race, 73.4%) and 53 boys (mean age at time of testing, 20.2 [7.3] days; birth weight, 3353 [413] g; birth length, 51.0 [2.4] cm; white race, 69.8%) were assessed and included in the study. At birth, girls were significantly shorter and weighed more than boys (both, P0.05). At ~1 month of age, body composition revealed that girls had significantly greater %fat (15.1% vs 12.7%; P0.05) and less fat-free mass (3182 [303] vs 3454 [361] g; P0.001) than did boys. At 3 months of age, girls continued to have significantly less fat-free mass (4379 [347] vs 4787 [310] g; P0.01) than did boys; however, by 6 months of age, no significant sex difference was observed in any body composition variable studied.In this small sample of healthy, full-term newborns, at ~1 month of age, statistically significant differences in %fat and fat-free mass existed between girls and boys; however, by 6 months of age, these differences no longer existed.

Background: The prevalence of obesity among children in the United States represents a pool of latent morbidity. Though the prevalence of obesity has increased in both boys and girls, the causes and consequences differ between the sexes. Thus, interventions proposed to treat and prevent childhood obesity will need to account for these differences. Objective: This review examines gender differences in the presentation of obesity in children and describes environmental, hormonal, and genetic factors that contribute to observed gender differences. Methods: A search of peer-reviewed, published literature was performed with PubMed for articles published from January 1974 through October 2008. Search terms used were obesity, sex, gender, hormones, family environment, body composition, adiposity, and genes. Studies of children aged 0 to 18 years were included, and only articles published in English were reviewed for consideration. Articles that illustrated gender differences in either the presentation or underlying mechanisms of obesity in children were reviewed for content, and their bibliographies were used to identify other relevant literature. Results: Gender differences in childhood obesity have been understudied partially because of how we define the categories of overweight and obesity. Close examination of studies revealed that gender differences were common, both before and during puberty. Boys and girls differ in body composition, patterns of weight gain, hormone biology, and the susceptibility to certain social, ethnic, genetic, and environmental factors. Conclusion: Our understanding of how gender differences in pediatric populations relate to the pathogenesis of obesity and the subsequent development of associated comorbid states is critical to developing and implementing both therapeutic and preventive interventions.

Background: Most studies of hypothalamic-pituitary-gonadal (HPG) function in illicit drug users either focus on men or do not consider the impact of HIV. Objective: This study investigated the relationships between cocaine and/or opiate use, HIV status, and HPG function in both men and women. Methods: Men and women between 18 and 50 years of age were stratified by sex, drug use, and HIV status. Information on demographics, HIV disease and treatment, and illicit drug use patterns was collected. To determine potential effects on HPG function, free testosterone (free T), estradiol, and gonadotropin concentrations were measured. Results: In a total of 197 men and women, free T concentrations were lower in men who used cocaine and/or opiates and in women infected with HIV Gonadotropin concentrations were elevated in seropositive men only. In women who received highly active antiretroviral therapy, HIV infection and illicit drug use had an additive or synergistic impact on free T concentrations. Conclusions: Our data reveal the importance of considering the independent effects of illicit drug use and HIV status for both men and women, so that risks may be identified and potential treatments designed for HPG dysfunction in these groups.

PurposeWe examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes.Materials and methodsA total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised.ResultsA large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged.ConclusionsAlthough many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted.

A review of gender role (GR) differentiation from early childhood through adulthood was conducted on males and females in general, as well as on females affected by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency or complete androgen insensitivity syndrome (CAIS). Additionally, retrospective and current, self-rated GR assessments were evaluated from women with CAH (n = 9) or CAIS (n = 12), and unaffected women and men ranging in age from 16 to 59 years. Overall, GR differentiation occurs in early childhood and persists through adulthood. With advanced age, this differentiation may evolve into androgyny or even become undifferentiated for the general population. While more studies of GR exist for girls and women with CAH compared to those affected by CAIS, some developmental patterns can be observed from the limited data that exist. First, girls and women with CAIS report a female GR that persists through adulthood. Second, girls and women with CAH are more likely to report less feminine/ more masculine play in childhood followed by interests in male-typical leisure activities and career choices in adulthood. However, our data indicate that women with CAH report more feminine/ less masculine patterns of GR with age. Self-reported GR for women with CAH was indistinguishable from that of women with CAIS at the time of study participation in adulthood. With the availability of effective medications for treating hormone deficiencies associated with CAH, affected women are expected to live a full lifespan. Thus, our understanding of psychosexual development into older age is warranted.

Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.

Limited attention has been paid to the potential impact of gender and injection drug use (IDU) on mood, quality of life, and neuropsychological performance in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Several studies that describe the natural history of HIV/AIDS in terms of mental health and neuropsychological ability have focused solely on men or have excluded injection drug users. Women and injection drug users are two groups for whom the incidence of HIV infection is increasing. Additionally, the National Academy of Sciences recently recommended that studies concerned with health-related research include males and females, and that researchers analyze their data for gender differences. The goals of the current study were to investigate possible relationships between HIV and IDU status and depressive symptoms, quality of life, and neuropsychological performance in women and men matched for age, race, and education. Overall, women reported more depressive symptoms than men, and this gender difference was most evident in women who were both infected with HIV and who were also injection drug users. Women and HIV-infected individuals reported the poorest quality of life scores. Women outperformed men on a measure of verbal memory and HIV(-) participants outperformed HIV(+) participants on a measure of perceptual speed. Finally, gender and HIV status interacted such that uninfected women performed the best, and infected men performed the worst, on a test of verbal memory. A better understanding of how men and women with different drug use profiles respond to HIV/AIDS may substantially improve survival, as well as aspects of daily functioning, of affected individuals. Thus, further study and development of treatment protocols targeted at including women and IDU are needed.

Cross-sex hormone treatment is an important component in medical treatment of transsexual people. Endocrinologists are often faced with designing treatment recommendations. Although guidelines from organizations, such as the Harry Benjamin International Gender Dysphoria Association, have been helpful, management remains complex and experience guided. We discuss the range of treatment used by transsexual people, the rationale behind these, and the expectation from such treatment. Recommendations from seven clinical research centers treating transsexual people are discussed. In addition, self-reported hormonal regimens from 25 male-to-female transsexual people and five female-to-male transsexual people are reported. Finally, the potential adverse effects of cross-sex hormone treatment of transsexual people are reviewed. In light of the complexity of managing treatment goals and adverse effects, the active involvement of a medical doctor experienced in cross-sex hormonal therapy is vital to ensure the safety of transsexual people.

Exposure to the phytoestrogen genistein (Indofine Chemical Co., Somerville, New Jersey) can disrupt normal male sexual differentiation. To determine if perinatal (that is gestation and lactation) genistein exposure at doses common in human diets alters masculinization we examined the development of the external genitalia, testes, wolffian ducts and sexual behavior in male rats exposed to genistein supplemented diets during early development.Female rats were fed a phytoestrogen-free diet supplemented with no genistein (free), a low genistein dose (low) or a high genistein dose (high) throughout gestation and lactation. Anogenital distance of male offspring was measured weekly from postnatal days 2 to 21. At puberty (postnatal day 40 to 45) preputial separation, and testis length and width of male offspring were measured. At age 70 days reproductive organ masses, plasma testosterone concentration, sperm counts and sexual behavior were assessed in male offspring. RESULTS Exposure to genistein resulted in temporary, prepubertal urogenital abnormalities at postnatal days 21 and 40. Males exposed to genistein had smaller anogenital distance and testis size, and delayed preputial separation. Perinatal exposure to genistein also caused long-term dysfunction in reproductive behavior, in which adult males exposed to genistein were less likely to mount, intromit and ejaculate during mating tests. Males exposed to genistein also had lower testosterone concentrations in adulthood.Perinatal genistein exposure results in transient and lasting alterations in masculinization of the reproductive system. These results extend our knowledge of the effects of early genistein exposure on male development and may have implications for human health in terms of potential relationships of endocrine disrupters and urogenital abnormalities thought to be increasing in incidence in boys and men.

Controversy concerning optimal treatment for individuals affected by syndromes of abnormal sex differentiation can best be resolved with knowledge about long-term medical, surgical, and psychosexual outcomes of patients. Follow-up information has recently been gathered on older cohorts of the following patient groups: (1) those affected by complete androgen insensitivity syndrome (CAIS) raised female and (2) those affected by congenital micropenis raised male or female. As a group, women with CAIS were satisfied with their female gender and sexual function. However, a need for better patient education was identified for this specific population. Most patients with congenital micropenis, whether raised male or female, were satisfied with their gender. Regardless of sex of rearing, dissatisfaction with the appearance and function of the genitalia as judged by both physicians and subjects was evident. For patients with congenital micropenis, male sex of rearing was concluded to be optimal because genital reconstructive surgery is not required with this choice.

Within the chronic medical illness literature, associations exist between caring for an affected child and parent mental health. The few studies examining both mothers and fathers provide mixed results. The purpose of this study is to examine associations between caregiver anxiety, depression, and parenting variables in caregivers of youth with SB as these relate to marital status, age, education, household income, work status, and child's severity of SB.The aim of this study is to examine associations between anxiety, depression, and parenting variables in caregivers of youth with spina bifida and how they relate to demographic and disease variables. Exploratory analyses examined the relationship between participation in support activities and depressive and anxious symptomatology and parenting characteristics.Eighty-four primary caregivers (49 mothers) of 51 youth with spina bifida completed measures of depressive and anxious symptomology, parenting stress, parent overprotection, and perceived child vulnerability.There were differences between mothers and fathers on several parenting characteristics; however, these were related more to marital status and employment than to gender of the caretaker per se. In the 33 married/remarried couples for whom both spouses participated, stress for the mothers was correlated with stress for the fathers. This correlation was strongest in the 12 married couples in which the mother works. Higher perceived vulnerability scores were reported in parents of SB patients in the younger age group, especially preschoolers (0-4 years). Parents of children with shunts reported more anxiety, depression and perceived child vulnerability. Both male and female caregivers of younger children reported significantly higher protectiveness scores. Involvement in recreational activities with other families affected by SB was associated with more positive parenting characteristics for mothers.Stress and protectiveness were found to be positively correlated (r0.6); depression, anxiety, and perceived vulnerability were not (0.3r-0.3). Overall, mothers reported more stress and anxiety than fathers. Higher perceived vulnerability scores were reported in parents of SB patients in the younger age group, especially preschoolers (0-4 years). Parents of children with shunts reported more anxiety, depression and perceived child vulnerability. Both male and female caregivers of younger children reported significantly higher protectiveness scores compared to caregivers of older children. Involvement in recreational activities with other families affected by SB was associated with more positive parenting characteristics for mothers. There were differences between mothers and fathers on several parenting characteristics; however, these were related more to marital status and employment than to gender of the caretaker per se. Limitations to the current study qualify our results and conclusions. Associations do not prove causation. Our measure of parent protection had a lower Cronbach's alpha score for male caregivers (0.68) than female caregivers (0.83), consistent with an examination of the factor structure of the PPS that found the measure to have a poor factor structure and limited reliability in samples with a chronic medical condition.Anxiety, depression, and parenting characteristics were differentially impacted by variables such as caregiver and child age, shunt status, and employment status/income for parents of youth with SB. Interventions to improve parenting skills and mental health of these caregivers can be designed to target specific needs of parents. Groups such as the Greater Oklahoma Disabled Sports Association (GODSA) offer real-world support to improve the lives of caregivers of SB children, and should be studied further to optimize outcomes for children.

Purpose/background To examine whether male and female caregivers of children with a disorder of sex development (DSD) differ in levels of anxious and depressive symptoms. Materials/methods Participants included 80 caregivers (40 males, 40 females) of 40 children with a DSD. Children were categorized based on illness characteristics including ambiguous genitalia, life-threatening, and life-threatening with ambiguous genitalia. Caregivers completed measures of anxious and depressive symptoms. Results A significant caregiver × diagnosis interaction for anxious symptoms emerged, with male caregivers of children with both ambiguous genitalia and a life-threatening condition reporting significantly lower levels of anxious symptoms than female caregivers of the same children. Conclusions The findings are surprising because of the low level of anxious symptoms reported by male caregivers of children with a complex DSD. It is possible that they have disengaged themselves from the child and/or diagnosis, causing their female counterparts to take on more responsibility.

Objectives: to document long-term medical, surgical and psychosexual outcome of individuals with congenital micropenis (13 males, 5 females). Methods: Physical measurements from childhood were collected retrospectively from medical records and at adulthood by physical examination. An adult psychosexual assessment was conducted with a written questionnaire and oral discussion. Results: Adult penile length was below the normal mean in all men. Three women had vaginoplasty resulting in normal length. All men reported good or fair erections but 50% were dissatisfied with their genitalia. Dissatisfaction with body image resulted from having a small penis (66%), inadequate body hair (50%), gynecomastia (33%) and youthful appearance (33%). Ten men were heterosexual, 1 homosexual and 2 bisexual. Among women, 4 (80%) were dissatisfied with their genitalia. Three women reported average libido with orgasm and were also heterosexual. Two women had no sexual interest or experience. Finally, males were masculine and females feminine in their gender-role identity, and both groups were satisfied with their sex of rearing. Conclusions: Regarding choice of gender, male sex of rearing can result in satisfactory genito-sexual function. Female gender can also result in success, however it requires extensive feminizing surgery.

A person’s sex can be considered across various levels. To illustrate, genes, hormones, and genitalia can all be considered physical markers of a person’s sex. In addition to physical markers, behaviors such as gender role, gender identity and sexual orientation can be perceived as stereotypically male or female. The purpose of this review is to summarize current knowledge of sexual differentiation which emphasizes genetic and hormonal mechanisms that result in male and female development of gonads and genitalia. Finally, consideration is given to associations between genetic sex, gonadal sex, and hormonal sex with gender.

We determined whether the degree of genital malformation at birth in children with a disorder of sex development is related to subsequent caregiver distress, specifically symptoms of depression and anxiety.A total of 66 caregivers of children with disorders of sex development were recruited from 3 centers that specialize in disorders of sex development medicine. The caregivers completed the Beck Depression Inventory, 2nd Edition and the Beck Anxiety Inventory. The child's Prader score at birth was determined by the child's treating pediatric endocrinologist and/or pediatric urologist at each institution.Results from the current study revealed that for caregivers of male children, under masculinization of the child's genitals at birth was significantly related to higher levels of subsequent caregiver depression. In contrast, over masculinization of the genitals of female children at birth was unrelated to caregiver depression or anxiety.These findings suggest that caregivers of male children with disorders of sex development may be at increased risk for psychological distress and could benefit from family based psychosocial interventions.

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods.

The profound hypogonadism due to androgen deprivation therapy for prostate cancer results in complications such as sexual dysfunction, poor quality of life, vasomotor symptoms and altered cognition. Since estrogen is associated with cardiovascular risks, phytoestrogens are being increasingly evaluated as a potential treatment for these adverse effects. We evaluated the effects of high dose isoflavones, equivalent to that consumed by Asian populations, on the aforementioned consequences of androgen deprivation therapy.A total of 33 men undergoing androgen deprivation therapy for prostate cancer were enrolled in this randomized, double-blind, placebo controlled, 12-week pilot trial. Participants were randomly assigned to receive 20 gm soy protein containing 160 mg total isoflavones (17) vs taste matched placebo, that is 20 gm whole milk protein (16). The study was performed at a tertiary care center in the United States.At baseline the groups were well matched in demographic parameters, sleep quality, cognition and overall quality of life. However, men in the isoflavone group had a higher baseline prevalence of hot flashes and poor intercourse satisfaction compared to those on placebo. At 12 weeks there were no significant differences between the 2 groups in any outcome measure.This pilot study of high dose isoflavones in androgen deprived men showed no significant improvement in cognition, vasomotor symptoms or any other aspect of quality of life measures compared to placebo. Future studies should use variable doses of isoflavones for a longer period before ruling out beneficial isoflavone effects in this population.

We used current methods of screening for prostate cancer, digital rectal examination and serum prostate specific antigen as an initial assessment of risk in a young group of adult 46,XY patients affected by disorders of sex development.Adult intersex patients older than 21 years, under long-term followup at the Pediatric Endocrinology Clinic of the Johns Hopkins Hospital, with a diagnosis of male psuedohermaphroditism and raised as male or female were included in analysis. After written consent all participants underwent digital rectal examination and blood sampling for prostate specific antigen and testosterone measurements.Prostate specific antigen values were available for analysis in 26 patients. Diagnoses included micropenis (8), complete androgen insensitivity syndrome (3), partial androgen insensitivity syndrome (9) and mixed gonadal dysgenesis (6). Of the 26 patients 9 had been raised as female (complete androgen insensitivity syndrome in 3, partial androgen insensitivity syndrome in 3, micropenis in 2 and mixed gonadal dysgenesis in 1). Mean patient age was 38 years (range 24 to 57). Serum prostate specific antigen was less than 0.1 ng/ml in 18 patients including the 9 reared as female. The remaining 8 patients had a prostate specific antigen of 0.1 to 0.9 ng/ml, were reared as male and had a mean age of 39.6 years (range 33 to 44). The diagnoses in this group consisted of micropenis (4), partial androgen insensitivity syndrome (2) and mixed gonadal dysgenesis (2). All patients had a palpable, small prostate gland with no abnormalities noted on digital rectal examination.This study found measurable prostate specific antigen in a subset of male intersex patients that were comparable to controls matched for age and race. We recommend that patients with 46,XY disorder of sex development, reared as male, be screened for prostate cancer in a manner similar to men not affected by disorder of sex development.

Self-rated degree of femininity and masculinity across development were evaluated for 40 adults affected by 46,XY disorders of sex development (DSDs) who presented at birth with a small phallus and perineoscrotal hypospadias, raised either male (n = 22) or female (n = 18). Most participants were confirmed or presumed to be affected by partial androgen insensitivity syndrome (n = 14), partial gonadal dysgenesis (n = 11), or were considered to have a poorly defined case of 46,XY DSD including ambiguous external genitalia (n = 15). Participants retrospectively evaluated their degree of masculinity and femininity during their childhood, adolescence, adulthood, and in the past 12 months of filling out a questionnaire pertaining to their psychosexual development. Participants raised male reported more masculinity than those raised female due to an increase in masculinization during adolescence and adulthood. Participants raised male also reported less femininity than those raised female throughout development. Participants raised female reported more femininity than those raised male due to an increase in feminization during adolescence and adulthood. Participants raised female also reported less masculinity than those raised male throughout development. These data support the proposition that some aspects of gender role (GR), such as masculinity and femininity, are capable of proceeding along female- or male-typic patterns depending on sex of rearing among individuals affected by specific types of 46,XY DSD. Furthermore, regardless of male or female rearing, GR increasingly corresponds with assigned sex as individuals proceed through sexual maturity and into adulthood. These results are consistent with the idea that socialization/learning contributes to GR development in humans in addition to data from others demonstrating endocrine influences.

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.

Purpose: We surveyed a clinic sample of adult 46,XY intersex patients regarding attitudes to clinical management policies. Materials and Methods: All adult former patients of 1 pediatric endocrine clinic in the eastern United States whose addresses could be obtained and who consented to participation were surveyed by a comprehensive written followup questionnaire. Three questions on attitudes concerning the desirability of a third gender category and the age at which genital surgery should be done were presented in the context of ratings of satisfaction with gender, genital status and sexual functioning. Results: A total of 72 English speaking patients with 46,XY, including 32 men and 40 women 18 to 60 years old, completed the questionnaire. The majority of respondents stated that they were mainly satisfied with being the assigned gender, did not have a time in life when they felt unsure about gender, did not agree to a third gender policy, did not think that the genitals looked unusual (although the majority of men rated their penis as too small), were somewhat or mainly satisfied with sexual functioning, did not agree that corrective genital surgery should be postponed to adulthood and stated that their genital surgeries should have been performed before adulthood, although there were some significant and important differences among subgroups. Conclusions: The majority of adult patients with intersexuality appeared to be satisfied with gender and genital status, and did not support major changes in the prevailing policy. However, a significant minority was dissatisfied and endorsed policy changes.

This study examined the impact of sex hormones on functional cerebral hemispheric lateralization and cognition in a group of male-to-female transsexuals receiving cross-sex hormone therapy compared to eugonadal men with a male gender identity. Cerebral lateralization was measured with a handedness questionnaire and a visual-split-field paradigm and cognitive tests sensitive to sex hormone exposure (identical pictures, 3-D mental rotation, building memory) were also administered. Endocrine measures on the day of participation for transsexual and control subjects included total testosterone, free testosterone, estradiol, gonadotropins, and sex hormone binding globulin concentrations. Compared to controls, male-to-female transsexuals had elevated estradiol and sex hormone binding globulin concentrations and suppressed testosterone concentrations. Transsexual subjects showed a trend toward less exclusive right-handedness than controls. No group differences were observed on the visual-split-field or cognitive tasks. No direct associations were observed between endocrine measures and the laterality measures and cognitive performance. Previous observations of female-typical patterns in cerebral lateralization and cognitive performance in male-to-female transsexuals were not found in the current study.

The purpose of this chapter is to review the presentation and management of patients affected by conditions of abnormal sex differentiation. First, the processes of normal sex differentiation are covered, followed by an overview of the various syndromes of abnormal sex differentiation, or intersex conditions, that can occur. These disorders are presented according to the following categories: patients who possess a 46,XX chromosome complement, those who possess a 46,XY chromosome complement, and individuals who present with an atypical sex chromosome complement (i.e. 45,XO or 45,X0/46,XY mosaicism). A description of the medical, surgical and psychological treatment options for people affected by various intersex conditions and reared as females are included. Practice points, based on research studies when available, are dispersed throughout the chapter. Additionally, information pertaining to relevant Internet websites and patient support groups are provided, so that medical staff can educate their patients about the availability of these resources.

Objectives. To identify and study adults (21 years or older) who have a 46,XY karyotype and presented as infants or children with genital ambiguity, including a small phallus and perineoscrotal hypospadias, reared male or female. Methods. Participants were classified according to the cause underlying their intersex condition based on review of medical and surgical records. Long-term medical and surgical outcome was assessed with a written questionnaire and physical examination. Long-term psychosexual development was assessed with a written questionnaire and semistructured interview. Results. Thirty-nine (72%) of 54 eligible patients participated. The cause underlying genital ambiguity of participants included partial androgen insensitivity syndrome (n = 14; 5 men and 9 women), partial gonadal dysgenesis (n = 11; 7 men and 4 women), and other intersex conditions. Men had significantly more genital surgeries (mean: 5.8) than women (mean: 2.1), and physician-rated cosmetic appearance of the genitalia was significantly worse for men than for women. The majority of participants were satisfied with their body image, and men and women did not differ on this measure. Most men (90%) and women (83%) had sexual experience with a partner. Men and women did not differ in their satisfaction with their sexual function. The majority of participants were exclusively heterosexual, and men considered themselves to be masculine and women considered themselves to be feminine. Finally, 23% of participants (5 men and 4 women) were dissatisfied with their sex of rearing determined by their parents and physicians. Conclusions. Either male or female sex of rearing can lead to successful long-term outcome for the majority of cases of severe genital ambiguity in 46,XY individuals. We discuss factors that should be considered by parents and physicians when deciding on a sex of rearing for such infants.

Adolescents with abnormal sexual differentiation or intersex conditions present a unique challenge to their healthcare providers. While sex refers to the biologic considerations that specify a person as male or female, gender refers to the sex of rearing. For the child with an intersex condition, sex may differ from gender, and as that child grows into adolescence, this may lead to many concerns, questions, and decisions. Although gender is usually fixed by adolescence, there will be those adolescents with intersex conditions wishing a gender reassignment during this period. Often a physician is the best resource for information and counsel to these young adults. Although most infants with ambiguous genitalia will have a karyotype done to determine gender identity, there are occasions when a gender discrepancy is not noticed until an adolescent presents with delayed pubarche. Regardless of the age at diagnosis, at adolescence, the physician must the address the medical consequences of infertility, bone health, and hormone replacement in addition to handling the heightened psychological concerns of gender identity during puberty. It is hoped that adolescents with intersex conditions will have the support and information necessary to allow them to live as normal a life as possible.

Over the past decade, knowledge of the genetic control of human sex differentiation has greately expanded our understanding of the developmental processes needed to form a male or female. The purpose of this review is to discuss how transcription factors are relevant to such processes. Additionally, an attempt is made to relate current knowledge of these factors with gender development of subjects with intersex conditions. Finally, we discuss how information about the genetic control of sex differentiation may contribute to decisions about medical treatment of individuals with conditions of abnormal sex differentiation.

Cortical asymmetry varies in degree and direction. Sex differences exist for both dimensions of asymmetry: males tend to exhibit more accentuated asymmetries and stronger right hemisphere dominance compared with females, while females typically exhibit more diffuse lateralization patterns and greater left hemisphere bias compared with males. The following review considers the effects of sex steroid hormones on the sexual dimorphism of cortical lateralization patterns in human and nonhuman animals. Several excellent papers exist which consider sexual dimorphism in cortical asymmetries for morphological, physiological or functional asymmetries alone. This paper attempts to consider influences of sex steroid hormones on cortical lateralization in a framework that includes morphology, physiology and function. Converging evidence from studies that incorporate varying methodologies and theoretical backgrounds indicates that sex steroid hormones are important for influencing cortical asymmetry. Although a mechanism has not yet been identified, testosterone is the most likely candidate to influence cortical dominance. © 1998 Elsevier Science Ltd. All rights reserved.

Two experiments investigated lateral asymmetries in infants' perception of contour-altered and contour-preserved melody changes. In the first study, 40 infants (8.5 months old) of right-handed parents were trained to respond to binaural melody changes with a head turn toward mechanized toy reinforcers. The subsequent test phase included monaural left-ear and right-ear presentations of the familiar melody and of a changed melody. Infants who heard a contour-altered change showed a left-ear advantage, whereas infants who heard a contour-preserved change showed a right-ear advantage. These effects were replicated with a different set of melodies in the second study. The pattern of lateralization for detection of melody changes in infants of right-handed parents resembles that previously found in right-handed adults and may reflect more general hemispheric processing differences in the early organization of auditory information processing.

Three experiments examined the capacity of European starlings to segregate perceptually 2 superimposed, intermixed auditory stimuli. The stimuli were 10-s song samples from 2 of 4 songbird species: European starling, brown thrasher, mockingbird, and nightingale. The birds first learned a discrimination between the intermixed song pairs. Then, they maintained the discrimination with novel song exemplars in the mixtures and when song stimuli for each species were presented alone. Performance fell, but remained above chance, when song pairs were mixed with the dawn chorus of bird song. The results show that starlings were identifying the songs of individual species within the baseline superimposed song pairs, a process of auditory stream segregation and scene analysis (A. S. Bregman, 1990).

Objectives. The objective of this study was to identify and study adults who have a 46,XY karyotype and presented as infants or children with variable degrees of undermasculinization of their genitalia (female genitalia, ambiguous genitalia, or micropenis). Participants’ knowledge of their condition, satisfaction with their knowledge, and desire for additional education about their intersex condition were assessed. Methods. Participants were classified according to the cause underlying their intersex condition based on review of medical and surgical records. Knowledge of medical condition, satisfaction with that knowledge, and desire for additional education were assessed with a written questionnaire and a semistructured interview. Results. Patients were ineligible for recruitment because of death (9%), because of developmental delay (12%), or because they were not located (27%). Among the 96 eligible patients, 78% participated. Approximately half of the men (53%) and women (54%) exhibited a good understanding of their history. Fewer women who have a 46,XY chromosome complement and were born with female genitalia were informed about their intersex condition (36% with complete androgen insensitivity syndrome) than were women who were born with masculinized genitalia such as micropenis (80%) or ambiguous genitalia (72%). More women (66%) than men (38%) were satisfied with their knowledge of their medical and surgical history. Conclusions. Almost half of the patients, reared male or female, were neither well informed about their medical and surgical history nor satisfied with their knowledge.