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Intersex/Disorders/Differences of sex development conditions have been recognized for millennia. An organized approach was adopted in the 1960–70s using the philosophy that gender identity was fluid and malleable. Consequences of this approach were the lack of disclosure, stigmatization, and excessive surgery to “normalize” the genitalia. Often this led to quality of life issues for those patients. There have been many modifications in approach since then to avoid the problems noted. There is consensus on many of these changes (e.g. disclosure) but continued controversy on others (e.g. the benefits of early surgery). This review summarizes the historical context and the current areas of consensus and controversy.

Testes were associated with maleness from antiquity, and ancient societies had fanciful myths about the origins of the sexes and about fetal sexual development. 17th century anatomists developed the concept that mammals developed from eggs and discovered sperm in semen; in 1878, Hertwig observed sperm entering eggs (of sea urchins), establishing the cellular basis of sex development. Individuals with atypical genitalia were known clinically in the 17th century, with much debate about their origins, but by the late 19th century it was generally accepted that gonads determined sex, and that sex determined gender role. Testosterone was isolated in 1935, and Alfred Jost showed that both circulating testosterone and diffusible anti-Mullerian hormone were needed for male development. Patients with apparent androgen insensitivity were reported in 1937 and shown to be unresponsive to exogenous androgen by Lawson Wilkins in 1957; androgen receptor mutations were reported in 1989. Steroidogenic errors were associated with differences in sex development (DSDs) starting in the 1940s, and finding mutations in the responsible enzymes explained many forms of hyper- and hypo-androgenism in both sexes. Sex chromosomes were identified in the early 20th century; Y was associated with maleness, and the responsible SRY gene was identified in 1991. Early efforts to manage patients with DSDs were confounded by philosophical perspectives on the relative roles of prenatal biology versus postnatal environment. Approaches to natal sex assignment evolved in the later 20th century and now emphasize a team approach based on data, not guessing, parental involvement, cultural considerations, and the acknowledgement of uncertainty.

PURPOSE A tetrahedron beam (TB) X-ray system with a linear X-ray source array and a linear detector array positioned orthogonal to each other may overcome the X-ray scattering problem of traditional cone-beam X-ray systems. We developed a TB imaging benchtop system using a linear array X-ray source to demonstrate the principle and benefits of TB imaging. METHODS A multi-pixel thermionic emission X-ray (MPTEX) source with 48 focal spots in 4-mm spacing was developed in-house. The X-ray beams are collimated to a stack of fan beams that are converged to a 6-mm wide multi-row photon-counting detector (PCD). The data collected with a sequential scan of the sources at a fixed view angle were synthesized to a 2D radiography image by a shift-and-add algorithm. The data collected with a full rotation of the system were reconstructed into 3D TB CT (TBCT) images using an Feldkamp, Davis, and Kress (FDK)-based computed tomography (CT) algorithm modified for the TB geometry. RESULTS With an 18.8-cm long source array and a 35-cm long detector array, the TB benchtop system provides a 25-cm cross-sectional and 8-cm axial field of view (FOV). The scatter-to-primary ratio (SPR) was approximately 17% for TB, as compared with 120% for cone beam geometry. The TBCT system enables reconstructions in two-dimensional radiography and three-dimensional volumetric CT. The TBCT images were free of "cupping" artifacts and have similar image quality as diagnostic helical CT. CONCLUSIONS A TB imaging benchtop imaging system was successfully developed with MPTEX source and PCD. Phantom and animal cadaver imaging demonstrated that the TB system can produce satisfactory radiographic X-ray images and 3D CT images with image quality comparable to diagnostic helical CTs.

Issues and concerns regarding surgery of the sexual-reproductive anatomy during infancy and early childhood are discussed using four actual examples. A case of a 46, XX infant with 21 hydroxylase deficiency congenital adrenal hyperplasia (CAH) with atypical (ambiguous) genitalia is discussed regarding timing and potential harms and benefits of surgery. We present the perspective of balancing the child's rights to bodily autonomy and right to an open future versus parents' decision making authority regarding what they perceive as their child's future best interests. The second case is a newborn with complete androgen insensitivity syndrome and we discuss the harms, benefits and timing of gonadectomy. The third case examines the physical and psychological impact of penile shaft hypospadias, raising the question of whether surgery is justified to prevent what may or may not be considered a permanent disability. The fourth case involves an adult woman with classic CAH, born with a urogenital sinus and clitoromegaly, who never had genital surgery and is now requesting vaginoplasty, but not clitoral reduction. The primary message of this article, as the previous articles in this series, is to encourage patient-family centered care that individualizes treatment guided by shared decision making. ispartof: JOURNAL OF PEDIATRIC UROLOGY vol:17 issue:3 pages:338-345 ispartof: location:England status: published

This report of a 46,XY patient born with a micropenis consistent with etiology from isolated congenital growth hormone deficiency is used to (1) raise the question regarding what degree testicular testosterone exposure to the central nervous system during fetal life and early infancy has on the development of male gender identity, regardless of gender of rearing; (2) suggest the obligatory nature of timely full disclosure of medical history; (3) emphasize that virtually all 46,XY infants with functional testes and a micropenis should be initially boys except some with partial androgen insensitivity syndrome; and (4) highlight the sustaining value of a positive long-term relationship with a trusted physician (R.M.B.). When this infant presented, it was commonly considered inappropriate to gender assign an infant male whose penis was so small that an adult size was expected to be inadequate, even if the karyotype was 46,XY, and testes were functional. Concomitantly, female gender assignment was considered the appropriate decision, believing that parental rearing in the assigned gender was considered the major factor determining established adult gender identity. Full disclosure of medical information was considered inappropriate. Progress in appreciating the complexities of gender identity development, which is not yet completely understood, and sexuality, coping ability, and outcome data has resulted in a change of practice in initial gender assignment. A 46,XY individual with functional testes and verified androgen responsiveness should be assigned and reared as male, regardless of penis size. Without androgen responsiveness, the multiple factors must be carefully considered and disclosed.

Disorders of sex development (DSD) replaced the terms intersex, hermaphroditism, pseudohermaphroditism, sex errors of the body, and ambiguous genitalia in 2006; however, the terminology remains controversial. The current genetic-based classification system of DSD highlights the importance of chromosomal analysis in diagnosis and management of individuals with DSD. Despite advances in the domain of genetics, there has been little change in the endocrine treatment of DSD over the last few decades. On the other hand, there has been an evolving dynamic on many fronts including debates about the efficiency and timing of medically and nonmedically necessary genital surgery on infants and children with a DSD diagnosis; creation of a resolution by the Council of Europe in 2013 on the protection of children’s rights to physical integrity, demanding no one be “subjected to unnecessary medical or surgical treatment that is cosmetic rather than vital for health during infancy or childhood”; more transparency from physicians and other health professionals with families and patients; and an emphasis on the value of shared decision-making on issues such as genital surgery. In essence, there has been an evolving shift to a patient- and family-centered approach with the goal of optimizing quality of life. The aims of this chapter are to (1) provide a concise update on the mechanisms controlling normal and abnormal sexual differentiation, (2) share a protocol used at our institution for the practical management of infants born with DSD, (3) provide information to guide the physician when making a DSD diagnosis and designing medical management, (4) provide new behavioral information on DSD, and (5) highlight current differences of opinion regarding the care of infants born with DSD.

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.

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported . For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age ; , respectively).

Disorders of sex development refer to a collection of congenital conditions in which atypical development of chromosomal, gonadal, or anatomic sex occurs. Studies of 46,XY DSD have focused largely on gender identity, gender role, and sexual orientation. Few studies have focused on other domains, such as physical and mental health, that may contribute to a person's quality of life. The current review focuses on information published since 1955 pertaining to psychological well-being, cognition, general health, fertility, and sexual function in people affected by androgen insensitivity syndromes, 5- reductase-2 deficiency, or 17 -hydroxysteroid dehydrogenase-3 deficiency—reared male or female. The complete form of androgen insensitivity syndrome has been the focus of the largest number of investigations in domains other than gender. Despite this, all of the conditions included in the current review are under-studied. Realms identified for further study include psychological well-being, cognitive abilities, general health, fertility, and sexual function. Such investigations would not only improve the quality of life for those affected by DSD but may also provide information for improving physical and mental health in the general population.

HBIGDA members' treatment of persons with disorders of sex development (DSD), was assessed by questionnaire. The response rate was 71%. Ninety-three members (40% of respondents) provided a variety of clinical services to all ages and to parents of children with a DSD condition. The majority of these 93 had seen just a few such individuals but ten HBIGDA members had seen 10 + in the previous two years. Fifteen members were on gender teams that managed infants born with various syndromes of DSD. Survey results show that HBIGDA members are involved in the care of persons with “sex-atypical variants of genital differentiation,” and that they desire continuing education on the topic.

This review article answers three questions relevant to the medical management and care of individuals born with complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), or a micropenis: (1) Do any of these individuals reassign themselves from their initial gender assignment? (2) Do more reassign than the ones who do not? (3) Is there evidence of gender dysphoria in those who do not self-initiate reassignment? Reviewed were all articles on CAIS, PAIS, and micropenis cited in K. J. Zucker (1999) plus articles published through 2004. There were no documented cases of gender change in individuals with CAIS (N= 156 females) or micropenis (N= 89: 79 males, 10 females). Nine (9.1%) out of 99 individuals with PAIS changed gender. Thus, self-initiated gender reassignment was rare. Gender dysphoria also appears to be a rare occurrence. The best predictor of adult gender identity in CAIS, PAIS, and micropenis is initial gender assignment.

The 2006 Consensus Statement on Management of Intersex Disorders incorporated all variations in sex development under one superordinate term, disorders of sex development (DSD), and called for care to be delivered by integrated teams that include behavioral health providers. This chapter proposes an integrated team care model that is patient and family centered and attempts to balance the dominating perspective that focuses almost exclusively on gender-related aspects of DSD with one that conceptualizes DSD as a congenital and chronic condition, akin to other pediatric conditions. Ideal DSD team structure and functions are described; emphasis is placed on integrating services and enhancing communication among members of the healthcare team and the family. Evaluation and treatment issues are identified, as well as the need for routine reassessment, given that the importance of particular domains (e.g., sharing information, fertility) varies with developmental stage. A strategy for selecting assessment instruments is outlined, and links are provided to databases of psychometrically robust measures of health-related quality of life as well as narrower domains of function. Because confusion remains, distinctions between DSD and transsexualism are delineated. Finally, barriers to the implementation of the proposed model are considered.

The aims of this chapter are the following: (1) provide a concise update on the mechanisms controlling normal and abnormal sexual differentiation, (2) provide a protocol used at our institution for practical management of infants born with DSD, (3) provide information to guide the physician on making a DSD diagnosis and its medical management, (4) provide new behavioral information on DSD, and (5) highlight current differences of opinions about the care of infants born with DSD. A discussion of infants who are born with DSD with normal-appearing genitalia is also included.

We describe how a gender specialist team managed the case of a disorder of sex development in a preterm infant where definitive diagnosis and gender assignment were delayed due to complications of prematurity, anemia, and severe intrauterine growth restriction.

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.

Physicians and other providers are often confronted with difficult decisions in the area of disclosure. This article examines a hypothetical situation relevant to the practice of pediatric endocrinology. The parents of a child with a disorder of sex development (DSD) wish the physician to treat their child, but without revealing key medical information to the child. Herein, we will explore the legal and ethical responsibilities of a provider to disclose information to an under-age DSD patient and to provide insight on when and how to tell the patient.

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported . For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age ; , respectively).

This paper describes an adolescent program for the management of sexually inappropriate behavior, a family-based, 16-week group intervention protocol. Also described are the ten individuals (ages 13-17) who completed this program. Outcome data generated from follow-up at six months post-treatment are presented.

The behavioral data reviewed herein must be viewed with caution. Although there are reports that adhere to rigorous methodology, these are the exception. Most reports do not adequately describe either the methodology used or their sample. Subjects are often of mixed endocrine diagnoses, and sometimes the results are of both boys and girls. All of these pitfalls make interpretation of results difficult and limiting. With this in mind, the following conclusions are offered. The majority of behavioral data on precocious puberty comes from studies of IPP in girls. Cognitively, IPP has been associated with average to high-average intelligence. Purportedly, the finding of lower visual-spatial skills than verbal skills in early maturing boys and girls has received equivocal support by cognitive studies of IPP individuals. Similarly, clear differences in hemispheric lateralization have not been demonstrated. Aside from increased somatic complaints during the nonmenstrual phases of their menstrual cycle, girls with IPP show a spectrum of behavior adjustments. Major psychopathology is rare. Clearly, their early development makes them look older than their actual age, which probably alters the expectations others have for them. Psychosexually, however, IPP girls develop in concert with their chronologic age and social experience, rather than their early biologic maturation. However, recent reports suggest a modest influence of hormones. In summary, these studies support an interactionist theory of human psychosexual development. Research data on IPP girls suggest that they do not significantly differ from girls who are early maturers but within the normal range. Research on these girls indicates that most negotiate their puberty without severe problems. There has been less research on IPP boys because it occurs so rarely. Most of what is understood about precocious puberty in boys comes from boys with precocious puberty secondary to poorly controlled CAH. Behavioral data on individuals with delayed puberty come almost exclusively from boys. Although CD appears to be the most frequently diagnosed form of delayed puberty and does not reflect a known pathologic process, men with CD as well as those with organic disorders appear to be at risk for psychosocial and psychosexual difficulties. These difficulties are not severe forms of psychopathology. Rather, they probably represent problems negotiating the expected adolescent lessons of psychosocial development with a physique that places them at a disadvantage. They clearly look younger than their actual chronologic age. Cognitively, as with the children with precocious puberty, there is no evidence of intellectual impairment associated with delayed puberty.(ABSTRACT TRUNCATED AT 400 WORDS)

We assessed the adult quality of life of five medical chart-selected genetic males (ages 29-34 years) assigned and reared as females due to ambiguity of the external genitalia. All five were treated following the traditional method proposed by John Money and colleagues in 1955, commonly referred to as the "optimal gender policy". The adult follow-up assessment included physical and endocrinological evaluation, completion of self-report questionnaires, and a semi-structured interview assessing gender identity, sexual experience and orientation. Quality of life domains assessed by questionnaire included health-related issues, satisfaction with health-care management, emotional distress, and relationship satisfaction. Vaginoplasty in four out of five patients was initially unsuccessful. Four patients had periodic lapses in adherence to hormone replacement therapy. Gender role behavior across development was masculine relative to norms for women. All participants reported a female gender identity without a history of gender dysphoria. The majority of participants (four of five) reported being sexually active and in long-term relationships (three heterosexual, one homosexual). Current emotional adaptation and health-related quality of life are within the normal range for four participants. Sex assignment of 46,XY individuals with ambiguous genitalia as females is compatible with a positive quality of life.

CASE. Following an uncomplicated 38 weeks pregnancy, a normal labor, and delivery with Apgar scores 8 and 9 at 1 and 5 minutes, respectively, a newborn was delivered with a birth weight of 6 pounds 5 ounces. The physical examination was unremarkable, except for complete absence of the penis. The scrotum appeared normal with bilateral palpable gonads of normal size. A voiding cystourethrogram demonstrated a normal bladder without uretero-vesical reflux; the contrast study revealed that urine partially emptied into the rectum and colon. The urethral meatus was positioned at the anterior anal verge. Karyotype was 46 XY. This is the third child for this couple. They have a 4-year-old boy and a 6-year-old girl. To which sex should this infant be assigned? Accompanying decisions concern disclosure of information to patient and family (what should be disclosed about the condition and its treatment and when?); surgery to have the genitalia match the sex assignment, or alternatively, female genital anatomy (what should be done and when?); psychological support of the patient and family (who should provide it and what model of care should be followed?); and involvement of other family members and friends (should they be told, and if so, what should they be told and when?).

Comprehensive guidelines for optimizing the outcomes for girls with Turner syndrome (TS) have been proposed (1–8). Much credit is owed to the advocacy positions taken by the TS Societies and their strong endorsement of clinical studies carried out by pediatric endocrinologists, psychologists, and geneticists. These collaborative efforts have resulted in significant advances in our understanding of the scope of the problems that may be encountered by girls with TS. They have also, led to the development of effective new treatment strategies. Credit must also be given to the parents of these children without whom our knowledge base would be incomplete.

Management of infants born with ambiguous sex organs requires the close collaboration of a team of professionals: pediatric endocrinologist, pediatric psychologist, gynecologist, and surgeon. The interdisciplinary teamwork of a group of professionals is described in the case of a patient announced at birth as a male but within days reannounced and reared as a female. Over the next 21 years, she became completely aware of her endocrine condition, including its medical classification (male pseudohermaphroditism), her chromosomal (46 XY) and gonadal (testes) status, and her early history of male sex assignment. The clinical management described herein helped this person deal effectively with her condition despite unsuccessful reconstructive vagal surgery. Substantiation of this is provided by the patient's personal comments.

Four black and three whilte families have a male-to-female transexual member surgically reassigned more than 5 years ag. The black families were more open than the white in declaring the reassignment within the family and community. Thereby they relieved themselves and the transexual member of a need for deception, defiance, or defensiveness, and they were less scheming and manipulative. Without the anxiety of concealment, they could feel more positive about sex reassignment as a form of rehabilitation. A formal public declaration of sex reassignment, analogous to a declared change of citizenship, would be advantageous in transexual rehabilitation.

Microphallus, also known as micropenis and partial agenesis of the penis, is a condition in which the corpora of the penis are agenetic or vestigial to a variable degree. There is no other defect of embryogenesis of the external genitalia.

In April, 1985, the FDA banned the distribution of pituitary growth hormone (hGH) because of the possibility that it was contaminated by a “slow virus”. All parents of children receiving hGH were notified by mail of the ban and subsequently invited to attend 3 meetings during vhich the ban, hGH, bio-engineered growth hormone (hGH) and the risks were discussed by physicians and psychologists, Approximately 10 months after the ban, we interviewed 32 children (30 males, 2 females, mean age 13.8 ± 2.5 years) and at least one parent about tie psychological impact of it. The mean treatement with hGH for these children was 3.0 ± 2.5 years. All had started on hGH. Results: (1) Parents reported a shift from positive to negative feelings about their children's GH treatment. Children reported a similar but less pronounced shift. (2) All parents reported being well informed about the reason for the tea, but 19% of the children were uninformed by parental choice. (3) Parents and children frequently voiced concern about the possible risk of neurological disease from GH given prior to the ban. Parents also voiced concern about their children not being able to grow tall because GH was banned. Children, too voiced this concern, (4) Most parents stated a concern about the safety of hGH. (5) Despite fears about prior GH treatment and present bGH treatment, all chose bGH therapy. Conclusion: Statural growth is seen as more important than possible risk of therapy. Our policy of immediate, full disclosure with opportunity for interactive discussion was considered beneficial by the parents.