Associations Between Fatigue and Endocrine and Non-endocrine Health Problems in Turner Syndrome: Cohort Study and Review.

CONTEXT: Turner syndrome (TS) is a rare chromosomal disorder characterized by gonadal dysfunction, short stature, and heart defects, among other features. Women with TS often suffer from severe fatigue, for which they are typically referred to endocrinologists. The diagnostic work-up is generally time-consuming and invasive, and it rarely solves the problem. To prevent the personal and financial burden of unnecessary diagnostic procedures, it is crucial to understand fatigue in TS. OBJECTIVE: To explore the association between fatigue and endocrine and non-endocrine comorbidities in a-for rare disorders-large group of women with TS. METHODS: 170 genetically confirmed women with TS who attended the TS Reference Center underwent a systematic health screening, including a structured interview, complete physical examination, biochemical measurements, perceived stress and fatigue questionnaires, and additional tests when indicated. RESULTS: Median (interquartile range) age was 32.6 (23.9-41.4) years. Severe fatigue was experienced by 1 in 3 women with TS. Liver enzyme disturbances and body mass index were significantly associated with higher fatigue scores. Perceived stress was highly correlated with fatigue. CONCLUSION: There was no association between fatigue and most endocrine and non-endocrine disorders, which implies that fatigue is only partly explained by somatic disorders. The high correlation between perceived stress and fatigue suggests that TS-related neuropsychological processes may play an important role in the etiology of fatigue in women with TS. We provide a practical algorithm for the endocrine, non-endocrine, and psychological approach to fatigue in women with TS.

Prenatal ultrasound finding of atypical genitalia: Counseling, genetic testing and outcomes.

OBJECTIVE: To report uptake of genetic counseling (GC) and prenatal genetic testing after the finding of atypical genitalia on prenatal ultrasound (US) and the clinical and genetic findings of these pregnancies. METHODS: A retrospective cohort study (2017-2019) of atypical fetal genitalia in a large expert center for disorders/differences of sex development. We describe counseling aspects, invasive prenatal testing, genetic and clinical outcome of fetuses apparently without [group 1, n = 22 (38%)] or with [group 2, n = 36 (62%)] additional anomalies on US. RESULTS: In group 1, 86% of parents opted for GC versus 72% in group 2, and respectively 58% and 15% of these parents refrained from invasive testing. Atypical genitalia were postnatally confirmed in 91% (group 1) and 64% (group 2), indicating a high rate of false positive US diagnosis of ambiguous genitalia. Four genetic diagnoses were established in group 1 (18%) and 10 in group 2 (28%). The total genetic diagnostic yield was 24%. No terminations of pregnancy occurred in group 1. CONCLUSIONS: For optimal care, referral for an expert fetal US scan, GC and invasive diagnostics including broad testing should be offered after prenatal detection of isolated atypical genitalia.

Sexual Self-Concept in Women with Disorders/Differences of Sex Development.

Many women born with disorders or differences of sex development (DSD) report sexual problems, in particular women who have undergone extensive genital reconstruction. Examining cognitions and emotions that hinder or promote sexuality may facilitate understanding these sexual problems and may contribute to the development of specific interventions. In this study, sexual self-concept, body image, and sexual functioning were investigated in relation to genital surgery. To conduct the study, the women's Sexual Self-Concept Scale was translated to Dutch. Evaluation of psychometric properties was conducted in a sample of healthy Belgian and Dutch women participating in an anonymous web-based survey (N = 589, Mdn age, 23 years). The resulting three-factor structure corresponded largely to that of the original version. Compared to control women, women born with a DSD who were included in the Dutch DSD study (N = 99, Mdn age, 26 years) described themselves as being less interested in sex and less sexually active. These women also harbored more negative emotions and cognitions regarding their sexuality and were less satisfied with their external genitalia. In women with a DSD, sexual self-concept was associated with compromised outcomes on sexual functioning and distress. Women who were in a steady relationship, and/or had been sexually active in the past 4 weeks had a more positive sexual self-concept, took a more active role in their sexual relationship, experienced more sexual desire and arousal and less sexual distress than women who were not involved in a partner relationship. Findings in this study indicate that cognitions and emotions related to sexual self-concept play a role in sexual functioning of women with a DSD. A cognitive behavioral counseling approach with focus on coping and exploration of their own sexual needs could prove useful in this group.

Determinants of impairments in functioning, fatigue, and participation ability in pediatric brain tumor survivors.

BACKGROUND: Pediatric brain tumor survivors (PBTS) experience disease- and treatment-related sequelae. We aimed to investigate the occurrence of participation limitations, impairments in functioning, fatigue, and the association between patient, tumor- and treatment-related factors and these outcomes. METHODS: Children (4-18 years) after treatment for a brain tumor between 2005 and 2014 at the Erasmus Medical Center, Rotterdam, the Netherlands, were eligible. The parent-reported Child and Family Follow-up Survey developed to measure participation and impairments in functioning in youth with acquired brain injury, was used. Fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale. Associations with patient, tumor- and treatment-related factors were explored using univariable analyses. RESULTS: Ninety-one PBTS (median age: 11.3 years [range: 9.5-14.1], time since treatment: 3.9 years [range: 4-6.2]) were included (response rate: 55%). Participation limitations were reported in 53% and were associated with impairments in functioning (15-67%) (P ≤ .01) and fatigue (P ≤ .03).Parent- and child-reported fatigue was increased compared to normative values (P ≤ .02). History of hydrocephalus was associated with increased fatigue (P ≤ .04). Younger age at diagnosis and longer time since diagnosis were associated with impairments in functioning and cognitive fatigue (P < .05).Participation limitations, impairments in functioning and fatigue were similar in PBTS who were <3 or ≥3 years since completion of treatment. CONCLUSION: More than half of PBTS reported limited participation ability, which is associated with impairments in functioning and fatigue. The complication hydrocephalus seems to lead to more fatigue. Participation limitations, impairments in functioning and fatigue appear not to diminish in the longer term.

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.

A value-based healthcare approach: Health-related quality of life and psychosocial functioning in women with Turner syndrome.

OBJECTIVE: As part of the value-based healthcare programme in our hospital, a set of patient-reported outcome measures was developed together with patients and implemented in the dedicated Turner Syndrome (TS) outpatient clinic. This study aims to investigate different aspects of health-related quality of life (HR-QoL) and psychosocial functioning in women with TS in order to establish new possible targets for therapy. DESIGN/PARTICIPANTS: A comprehensive set of questionnaires (EQ-5D, PSS-10, CIS-20, Ferti-QoL, FSFI) was developed and used to capture different aspects of HR-QoL and psychosocial functioning in a large cohort of adult women with Turner syndrome. All consecutive women, ≥18 years, who visited the outpatient clinic of our tertiary centre were eligible for inclusion. RESULTS: Of the eligible 201 women who were invited to participate, 177 women (age 34 ± 12 years, mean ± SD) completed at least one of the validated questionnaires (88%). Women with TS reported a lower health-related quality of life (EQ-5D: 0.857 vs 0.892, P = .003), perceived more stress (PSS-10:14.7 vs 13.3; P = .012) and experienced increased fatigue (CIS-20: P < .001) compared to the general Dutch population. A relationship between noncardiac comorbidities (eg diabetes, orthopaedic complaints) and HR-QoL was found (R = .508). CONCLUSIONS: We showed that TS women suffer from impaired HR-QoL, more perceived stress and increased fatigue compared to healthy controls. A relationship between noncardiac comorbidities and HR-QoL was found. Especially perceived stress and increased fatigue can be considered targets for improvement of HR-QoL in TS women.

Long-Term Cortisol Exposure and Associations With Height and Comorbidities in Turner Syndrome.

CONTEXT: Turner syndrome (TS) usually manifests in traits as short stature and premature ovarian failure. Many patients also have an increased risk of cardiometabolic disorders and psychological distress, which are features that overlap with those of a prolonged state of hypercortisolism. OBJECTIVE: To investigate whether TS is associated with increased long-term cortisol concentrations as measured in scalp hair and whether these are linked to cardiometabolic and psychological parameters. DESIGN: Prospective observational case-control study. SETTING: Academic outpatient TS expertise center. PARTICIPANTS: Fifty-five patients with TS (53% 45,X karyotype), and 110 age-matched female community control subjects from the general population-based Lifelines cohort study. MAIN OUTCOME MEASURES: Hair cortisol concentrations (HCC), anthropometrics, biochemical parameters, and psychological questionnaires for perceived stress (Perceived Stress Scale-14), fatigue (Checklist Individual Strength-20), and health-related quality of life (RAND-36). RESULTS: Compared with control subjects, patients with TS had higher HCC [geometric mean, 3.51 pg/mg (95% CI, 2.64 to 4.65) vs 2.39 pg/mg (2.13 to 2.68); P = 0.003] and a worse cardiometabolic profile in terms of fasting glucose, and triglycerides. HCC was only associated with total cholesterol levels (standardized ß = 0.294; P = 0.047) and was not associated with the psychological outcomes. A higher HCC was inversely associated with height only in patients with TS (standardized ß = -0.307; P = 0.023). CONCLUSION: Patients with TS are chronically exposed to higher cortisol levels, which is associated with short stature and increased total cholesterol levels, and potentially contributes to the known elevated cardiovascular disease risk.

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.

Multiparameter Investigation of a 46,XX/46,XY Tetragametic Chimeric Phenotypical Male Patient with Bilateral Scrotal Ovotestes and Ovulatory Activity.

We report on an adult male initially presenting with gynecomastia and a painless scrotal mass without additional genital anomalies. Hyperpigmentation of the skin following the Blaschko's lines was identified. He underwent gonadectomy because of suspected cancer. Histological analyses revealed an ovotestis with ovulatory activity confirmed by immunohistochemistry with multiple markers. Karyotyping of cultured peripheral blood lymphocytes and a buccal smear revealed a 46,XX/46,XY chimeric constitution with different percentages. Multiple molecular analyses as well as blood typing implied a tetragametic origin. After the unilateral gonadectomy, the patient developed recurrent painful cystic swellings of the remaining gonad. Because of the wish to preserve hormonal activity as well as future fertility, the patient underwent surgical resection of a cystic gonadal area. The removed tissue showed ovulation-related features in addition to both testicular and ovarian tissue, diagnosed as an ovotestis. Testosterone therapy was initiated to suppress the persistently elevated gonadotropins and thereby suppress ovarian activity. During treatment, the recurrent pain complaints and cystic swellings ceased, although gonadotropin levels were not fully suppressed. Based on these observations, the importance of a detailed genetic and pathological diagnosis and the clinical dilemmas including the pros and cons of personalized treatment with gonadal preservative surgery are discussed.

Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development.

The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support.

Health-related quality of life and emotional problems in children surviving brain tumor treatment: A descriptive study of 2 cohorts.

The survival of childhood brain tumors has improved in the past 30 years, but acquired brain injury due to damage caused by tumor invasion and side effects of different treatment modalities frequently occurs. This study focused on residual impairments, health-related quality of life (HRQoL), and emotional and behavioral problems in 2 cohorts of survivors diagnosed and treated for various types of brain tumors. Survivors in the 2004 cohort visited the Erasmus Medical Centre for standardized follow-up between 2003 and 2004, and in the 2014 cohort, between 2012 and 2014. Data of neurologically impairments of all children were extracted from medical records. Parents and survivors filled out questionnaires on quality of life and emotional and behavioral problems. In both cohorts, approximately 55% of the survivors displayed neurologic impairments. In comparison with the healthy reference group, a reduced parent-reported quality of life was found on the Motor, Cognition, and Autonomy (Cohort 2004) scales. Comparison between the cohorts showed that parents in the 2004 cohort reported a higher HRQoL on the Motor and Cognitive functioning scales. In the 2014 cohort, children reported less negative emotions than healthy children. No increase in emotional or behavioral problems were reported by children in both cohorts, whereas parents reported problems in social functioning and isolation related to a delay in emotional development. Children surviving brain tumor treatment have a reduced quality of life. The authors therefore recommend regular screening of HRQoL and emotional and behavioral problems and referral to specific aftercare.

Psychosocial well-being in Dutch adults with disorders of sex development.

OBJECTIVE: Atypical sex development is associated with psychosocial vulnerability. We investigated psychosocial well-being in individuals with disorders of sex development (DSD) and hypothesized that psychosocial well-being was related to degree of genital atypicality at birth. METHODS: 120 male (n=16) and female (n=104) persons with DSD, aged 14-60 years, participated in a follow-up audit on psychosocial well-being. They were stratified in: women with 1) 46,XY and female genitalia, 2) 46,XY or 46,XX and atypical genitalia, and 3) men with 46,XY and atypical genitalia. We used the Illness Cognition Questionnaire (ICQ), Checklist Individual Strength (CIS8R), TNO-AZL Quality of Life questionnaire (TAAQOL), Adult Self-Report (ASR), and the Rosenberg Self-Esteem Scale (RSES). RESULTS: Data were compared to reference groups. Participants generally were coping well with DSD (ICQ). Women with DSD reported elevated levels of fatigue (CIS8R) and slightly more attention and memory problems (TAAQOL, ASR). Women with atypical genitalia reported more emotional and behavioral problems. On the ASR Rule-breaking Behavior and Antisocial Personality scales, these women had similar scores as reference men. Women with DSD reported a higher self-esteem (RSES). No differences in psychosocial well-being were found between men with DSD and reference men. CONCLUSION: Individuals with DSD across all diagnostic groups generally reported a good psychosocial well-being. The results further suggest involvement of prenatal androgens in the development of personality traits related to assertiveness and egocentricity. We recommend that individuals with a DSD and their families are involved in decision-making processes and have access to multidisciplinary care.

Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.

Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure.

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

In most Western countries, clinical management of disorders of sex development (DSD), including ambiguous genitalia, begins at diagnosis soon after birth. For many Indonesian patients born with ambiguous genitalia, limited medical treatment is available. Consequently, affected individuals are raised with ambiguous genitalia and atypical secondary sex characteristics. 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 for gender, age, and residential setting (rural, suburban, or urban). 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 development 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 treatment prior to this study. We observed a gender change in all age 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 procedures 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 Behavioral 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 dissatisfaction 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 frequencies, 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 frequencies 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 ostracism 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.

Long-term outcomes in males with disorders of sex development.

PURPOSE: Indications that the prenatal action of testosterone in the brain is an important determinant of gender development and improved reconstructive techniques have caused a shift in male gender assignments in patients with 46XY disorders of sex development. We report long-term outcome data on psychosexual development and sexual function of these individuals in a cross-sectional study. MATERIALS AND METHODS: Physical status of 14 men with a mean age of 25 years with disorders of sex development was assessed by structured interview and physical examination. Psychosexual outcome was evaluated by questionnaires and compared to a control group of 46 healthy, age matched men. RESULTS: A total of 13 men underwent 1 to 6 (mean 2) genital surgeries. Mean age at first surgery was 2.7 years. Mean penile length was 6.6 cm. All men reported erections and were able to experience orgasms. Ejaculatory dysfunction was reported by 7 men. Mean penile length was 7.9 cm in patients who were able to achieve penetrative intercourse and 4.9 cm in those who were not. Meatus was glanular in 5 patients, coronal in 7 and at the distal shaft in 1. Compared to controls, men with disorders of sex development were less satisfied with the appearance of the penis and scrotum but not with total body image. These patients reported decreased sexual desire and activities. CONCLUSIONS: Outcome in this group of men with disorders of sex development was poor regarding penile length, ejaculation, satisfaction with external genitalia and frequency of sexual activity. Other aspects, such as overall body image and psychosexual functioning, showed no difference from controls.

Severity of virilization is associated with cosmetic appearance and sexual function in women with congenital adrenal hyperplasia: a cross-sectional study.

INTRODUCTION: Women with the classical form of congenital adrenal hyperplasia (CAH) are born with different degrees of virilization of the external genitalia. Feminizing surgery is often performed in childhood to change the appearance of the genitalia and to enable penile-vaginal intercourse later in life. There are suggestions that this affects sexual functioning. AIMS: The aim is to study the anatomical, surgical, cosmetic, and psychosexual outcomes in women with CAH. METHODS: Forty women with CAH, aged over 15 years, from two referral centers for management of Disorders of Sex Development in the Netherlands were included. Physical and functional status were assessed by a gynecological interview and examination. Sexual functioning was assessed with the Female Sexual Function Index and Female Sexual Distress Scale-Revised scales and compared with a reference group. MEAN OUTCOME MEASURES: Surgery performed, anatomy, cosmetic score, sexual function and distress. RESULTS: Thirty-six of the 40 women had undergone feminizing surgery; 25 women (69%) underwent more than one operation. Resurgery was performed in seven of the 13 (54%) women who had had a single-stage procedure. Anatomical assessment showed reasonable outcomes. Multiple linear regression showed that only level of confluence had a significant effect on cosmetic outcome, the impact depending on the number of surgeries performed. Cosmetic evaluations did not differ between the women and the gynecologists. Only 20 women had experience of intercourse. Eight women reported dyspareunia; seven women reported urinary incontinence. The women's perceived sexual functioning was less satisfactory than in the reference group, and they reported more sexual distress. CONCLUSION: The level of confluence was the major determinant for cosmetic outcome; the impact depended on the number of surgeries performed. Fifty-four percent of the women required resurgery after a single-stage procedure in childhood. Anatomical assessment showed reasonable outcomes. The women evaluated their sexual functioning and functional outcome less favorable than the reference group, and they experienced less often sexual intercourse.

Long-term psychosexual and anatomical outcome after vaginal dilation or vaginoplasty: a comparative study.

INTRODUCTION: In patients with disorders of sex development requiring creation of a neovagina, a number of techniques are available, including surgical vaginoplasty and self-dilation therapy. Vaginal dilation therapy has been recommended as a first-line treatment because of its less invasive character and high success rate. However, no data exist on long-term psychosexual functioning after vaginal dilation as compared with that after vaginal surgery. AIMS: The aim of this study is to compare the psychosexual and anatomical outcome of women with congenital vaginal hypoplasia followed in the same clinical setting after vaginoplasty with that after vaginal dilation. METHODS: The sexual quality of life of 35 women at least 2 years after vaginoplasty (N = 15), vaginal dilation therapy (N = 8), or coital dilation/no treatment (N = 12) was investigated and compared with the Dutch test validation population (as control). MAIN OUTCOME MEASURES: Psychosexual functioning was assessed with the female sexual Function index, the female sexual distress scale-revised, and a semi-structured interview. A gynecological examination was performed to determine the anatomical outcome after both vaginal treatment regimens. RESULTS: After either treatment, 26% of these women had a shortened vaginal length of less than 6.6 cm, i.e., more than two standard deviations below the published mean value (9.6 ± 1.5 cm). Irrespective of the treatment, 47% of the patients had (a) sexual dysfunction(s) and experienced sexual distress. However, after vaginoplasty, patients reported significantly more problems with lubrication (P = 0.025) than after self-dilation therapy. CONCLUSION: Both psychological and physical factors are predisposing for sexual difficulties. To optimize psychosexual comfort, the clinical management of women with vaginal hypoplasia needs to be multidisciplinary and individually tailored. With high success rates reported, vaginal dilation should remain the cornerstone of treatment.

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.