Gender Development in Indonesian Children, Adolescents, and Adults with Disorders of Sex Development

Abstract In most Western countries, clinical management of disorders of sex development (DSD), including ambiguous gen-italia, begins at diagnosis soon after birth. For many Indonesian patients born with ambiguous genitalia, limited medical treat-ment is available. Consequently, affected individuals are raised with ambiguous genitalia and atypical secondary sex character-istics. We investigated gender identity and gender role behavior in 118 Indonesian subjects (77 males, 41 females) with different types of DSD in comparison with 118 healthy controls matched forgender,age,andresidentialsetting(rural,suburban,orurban).In Study 1, we report on methodological aspects of the investigation, including scale adaptation, pilot testing, and determining reliability and validity of measures. In Study 2, we report on gender devel-opment in 60 children (42 boys, 18 girls), 24 adolescents (15 boys, 9 girls), and 34 adults (19 men, 15 women) with DSD. The majority of participants with DSD never received any medical or surgical treatmentpriortothisstudy.Weobservedagenderchangeinallage groups, with the greatest incidence in adults. Among patients who changed, most changed from female to male, possessed a 46,XY karyotype, and had experienced significant masculinization during life. Gender identity confusion and cross-gender behavior was more frequently observed in children with DSD raised as girls compared to boys. Puberty and associated masculinization were related to gender problems in individuals with 46,XY DSD raised female. An integrated clinical and psychological follow-up on gender outcome is necessary prior to puberty and adulthood

Emotional and behavioral problems in late-identified Indonesian patients with disorders of sex development

Objective: The aim of this study is to investigate emotional and behavioral problems among Indonesian patients with disorders of sex development (DSD) who recently came under clinical management. As diagnostic proce-dures and treatment had been delayed, patients progressively developed ambiguous bodies, difficult to conceal from outsiders. Method: We compared 118 Indonesian patients with DSD aged 6–41 years (60 children, 24 adolescents, 34 adults) and 118 healthy control subjects matched for age, gender, and residential settings. We used the Child Be-havioral Checklist (CBCL), Youth Self-Report (YSR), and Adult Self-Report (ASR) to examine differences between patient and control groups as well as differences within patients groups. Results: On the CBCL, parents of young children with DSD reported significantly more emotional and behavioral problems than parents of matched control. Parents of daughters with CAH reported that their daughters withdrew themselves from social interactions. On the ASR, adults with DSD reported significantly more internalizing problems than controls, particularly anxiety and depression. No other differences in emotional functioning were found across different diagnostic groups. Conclusions: Indonesian patients with DSD who were untreated for most of their lives suffered more emotional and behavioral problems than matched controls. Differences and similarities between our findings and observations in patients from Western countries will be discussed

Body Image and Sexuality in Indonesian Adults with a Disorder of Sex Development (DSD)

In Indonesia, disorders of sex development (DSDs) are not well recognized and medical care for affected individuals is scarce. Consequently, many patients live with ambiguous genitalia and appearance. We compared reported outcomes on body image, sexual functioning, and sexual orientation of 39 adults with DSDs (aged 18 to 41) and 39 healthy controls matched for gender, age, and residential setting (urban, suburban, rural). Differences in gender and treatment status (treated or untreated) were also explored. On body image, adults with DSDs reported dissat-isfaction with sex-related body parts. Compared to the matched controls, women with DSDs reported greater sexual distress, and men with DSDs reported lower erectile and ejaculation fre-quencies, and more dissatisfaction with sexual life but not with sexual desire and activities. Men with DSDs who had undergone genital surgery reported higher erectile and ejaculation frequen-cies than untreated men. More women than men in the DSDs group reported a nonexclusive heterosexual orientation. DSDs and infertility had a great impact on sexuality. Fear of ostra-cism complicated DSD acceptance. Findings were compared to those of Western studies. Based on these results, education about DSDs and their psychosexual consequences may help reduce the sexual distress and problems in adults with DSDs and improve quality of life

Do Surgical Interventions Influence Psychosexual and Cosmetic Outcomes in Women with Disorders of Sex Development?

Clinical practice developed to promote psychosexual well-being in DSD is under scrutiny. Although techniques for genital surgery have much improved lately, long-term studies on psychosexual functioning and cosmetic outcome on which to base treatment and counseling are scarce. We studied 91 women with a DSD. Feminizing surgery was performed in 64% of the women; in 60% of them, resurgery in puberty was needed after a single-stage procedure. Both patients and gynecologists were satisfied with the cosmetic appearance of the genitalia. However, forty percent of these females experienced sexuality-related distress and 66% was at risk for developing a sexual dysfunction, whether they had surgery or not. Recognizing the difficulty of accurate assessment, our data indicate that feminizing surgery does not seem to improve nor hamper psychosexual outcome, especially in patients with severe virilization

Quality of Life in Late-Treated Patients With Disorders of Sex Development: Insights for Patient-Centered Care

Background: Patients with a disorder of sex development (DSD) are born with atypical genitals or may develop atypical genitals and atypical body appearance, if left untreated. Health related quality of life (HRQoL) was assessed in Indonesian patients to whom diagnostic procedures and medical intervention had been delayed.Method: Comparison of 118 patients born with DSD, aged 6–41 years (60 children, 24 adolescents, and 34 adults) and 118 healthy control subjects matched for gender, age, and residential setting. HRQoL was measured using a translation of the TACQOL/TAAQOL.Results: According to parental and children's report, children with DSD reported more problems in social functioning and had less positive moods. Girls, in particular, reported problems in cognitive functioning. Adult patients reported more depressive moods, especially women, who reported more anger. No differences were found between in the adolescent groups.Conclusion: The data suggest that Indonesian children with DSD experienced more problems in social contact than non-affected Indonesian children, whereas Indonesian adults with DSD suffered from negative emotions more often than non-affected Indonesians. These findings on HRQoL are in line with findings on emotional functioning

Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development

We present key points from the updated Dutch-Flemish guideline on comprehensive diagnostics in disorders/differences of sex development (DSD) that have not been widely addressed in the current (inter)national literature. These points are of interest to physicians working in DSD (expert) centres and to professionals who come across persons with a DSD but have no (or limited) experience in this area. The Dutch-Flemish guideline is based on internationally accepted principles. Recent initiatives striving for uniform high-quality care across Europe, and beyond, such as the completed COST action 1303 and the European Reference Network for rare endocrine conditions (EndoERN), have generated several excellent papers covering nearly all aspects of DSD. The Dutch-Flemish guideline follows these international consensus papers and covers a number of other topics relevant to daily practice. For instance, although next-generation sequencing (NGS)-based molecular diagnostics are becoming the gold standard for genetic evaluation, it can be difficult to prove variant causality or relate the genotype to the clinical presentation. Network formation and centralisation are essential to promote functional studies that assess the effects of genetic variants and to the correct histological assessment of gonadal material from DSD patients, as well as allowing for maximisation of expertise and possible cost reductions. The Dutch-Flemish guidelines uniquely address three aspects of DSD. First, we propose an algorithm for counselling and diagnostic evaluation when a DSD is suspected prenatally, a clinical situation that is becoming more common. Referral to ultrasound sonographers and obstetricians who are part of a DSD team is increasingly important here. Second, we pay special attention to healthcare professionals not working within a DSD centre as they are often the first to diagnose or suspect a DSD, but are not regularly exposed to DSDs and may have limited experience. Their thoughtful communication to patients, carers and colleagues, and the accessibility of protocols for first-line management and efficient referral are essential. Careful communication in the prenatal to neonatal period and the adolescent to adult transition are equally important and relatively under-reported in the literature. Third, we discuss the timing of (NGS-based) molecular diagnostics in the initial workup of new patients and in people with a diagnosis made solely on clinical grounds or those who had earlier genetic testing that is not compatible with current state-of-the-art diagnostics

Addressing gaps in care of people with conditions affecting sex development and maturation

Differences of sex development are conditions with discrepancies between chromosomal, gonadal and phenotypic sex. In congenital hypogonadotropic hypogonadism, a lack of gonadotropin activity results primarily in the absence of pubertal development with prenatal sex development being (almost) unaffected in most patients. To expedite progress in the care of people affected by differences of sex development and congenital hypogonadotropic hypogonadism, the European Union has funded a number of scientific networks. Two Actions of the Cooperation of Science and Technology (COST) programmes - DSDnet (BM1303) and GnRH Network (BM1105) - provided the framework for ground-breaking research and allowed the development of position papers on diagnostic procedures and special laboratory analyses as well as clinical management. Both Actions developed educational programmes to increase expertise and promote interest in this area of science and medicine. In this Perspective article, we discuss the success of the COST Actions DSDnet and GnRH Network and the European Reference Network for Rare Endocrine Conditions (Endo-ERN), and provide recommendations for future research