Arianne B. Dessens

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 womens 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.

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.

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.

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.

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.

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.

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.

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.

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.