Sociale gevolgen

1988 Nielsen et al.
Klinefelter Syndrome(N=30)

15 of the 30 participants fall in the category ‘unskilled labourer’, four are labeled as ‘disablement pensioner’.

• 6 Skilled labourer
• 15 Unskilled labourer
• 5 Apprentice/student
• 4 Disablement pensioner

Nielsen J, Pelsen B, Sørensen K. Follow-up of 30 Klinefelter males treated with testosterone. Clinical Genetics. 1988;33(4):262-269. https://doi.org/10.1111/j.1399-0004.1988.tb03447.x.

2006 Carel et al.
Turner Syndrome (N=566)

2006 Johannsen et al.
Women with DSD (N=70), with CAIS (n=11), Virilized females (n=16). CAH (n=40), GD (n=3)

• Overall, present relationships were significantly less frequent in patients (n=41) than in controls (n=54, P=0.02)”
• “A tendency towards a higher frequency of counseling due to severe symptoms was found in the patient group as compared with their matched controls (P=0.06)”
• “Previous suicidal thoughts were reported significantly more frequent in the patient group (n=26) and in the operated controls (n=3), as compared with the healthy controls (n=9), PZ0.002 and 0.05 respectively. Previous suicidal thoughts were distributed unevenly among patients with higher frequencies in the 46,XX- and 46,XY-virilized females (P=0.008) and CAH females (P=0.03), as compared with their controls, while the CAIS and GD females had lower frequencies. The frequency of suicidal thoughts did not differ between patients and operated controls (P=0.67) or between patient subgroups (P=0.11).”
• “A history of suicidal attempt was reported in 11.6% of the patients and 4.3% of their controls, but in none of the operated controls. Median age at first suicidal attempt was 19.5 years (range 16–34) in the patients and 18.0 years (range 17–19) in the controls. Among patient subgroups, suicidal attempts were primarily seen in the CAH group (P=0.10 as compared with their controls),”
• “The mean anxiety score was significantly higher in the patients than in the controls (P=0.03) with the largest difference found between CAH females and their controls (P=0.01), while CAIS females had lower scores.”

Johannsen TH, Ripa CP, Mortensen EL, Main KM. Quality of life in 70 women with disorders of sex development. European Journal of Endocrinology. 2006;155(6):877-885. https://doi.org/10.1530/eje.1.02294

2007 De Vries at al. (Review)
CAH XX female (n=95), CAH XX Male (n=14), PAIS (n=77), only 12 year and older

Rejecting the assigned gender is seen as a genderidentity issue:

• CAH 46, XX raised female N=95: “ten showed serious gender identity problems, five made a gender change”
• CAH 46,XX raised male N=14: “Of them three identified themselves as females or were gender dysphoric.”
• PAIS 46,XY N=77: “77 PAIS cases identified as 12 years of age or older, (43 assigned female neonatally or physician imposed reassigned female before age 18 months, and 34 assigned male neonatally or physician imposed reassigned male before age 18 months), nine opted to change their gender later in life or developed gender dysphoria. Gender changes were from male to female in five cases and three were from female to male. All gender changes took place in adulthood. One female raised PAIS patient developed gender dysphoria but did not change her gender”.
• “Total: Of all the female-raised 46,XY subjects with different DSD (n = 260) described in this review, 42,3 % (n = 110) developed gender identity problems in adolescence or adulthood. Of the male-raised 46,XY subjects with different DSD (n = 436) described in this review, only 0.2 % (n = 1) possibly developed gender identity problems. Of the male-raised 46,XX subjects with CAH (n = 14), 21.4% (n = 3) developed problems. Of the female raised 46,XX subjects with CAH (n =217), 4.6 % (n = 10) developed serious gender identity problems.”

de Vries A, Doreleijers T, Cohen-Kettenis P. Disorders of sex development and gender identity outcome in adolescence and adulthood: understanding gender identity development and its clinical implications. Pediatric Endocrinology Reviews. 2007;4(4):343-351. https://www.ncbi.nlm.nih.gov/pubmed/17643082

2008 Schönbucher et al. (Review)
Hypospadias

• The findings regarding psychosexual development, however, clearly demonstrate that boys with hypospadias suffer from negative genital appraisal and sexual inhibitions.
• The findings on the significance of medical factors are likewise inconsistent. Overall, they suggest that medical characteristics bear a rather small influence on the psychosocial and psychosexual outcome. It is important to note that there is no empirical evidence that corrective surgery at the youngest possible age leads to a better psychological development. Thus, empirical results do not support the early surgical interventions, which pediatric urologist recommend for (APA, 1996; Zavitsanakis & Gougoudi, 2004).

Schönbucher VB, Weber DM, Landolt MA. Psychosocial adjustment, health-related quality of life, and psychosexual development of boys with hypospadias: a systematic review. Journal of pediatric psychology. 2008;33(5):520-535. https://doi.org/10.1093/jpepsy/jsm098

2009 Schützmann et al.
DSD (N=37): 17ß-HSD (n=2), 5a-RD (n=3), CAIS (n=5), PAIS (n=6), GD (n=10), CAH (n=11)

• “Our results suggest that adults with DSD are markedly psychologically distressed with rates of suicidal tendencies and self-harming behavior on a level comparable to non-DSD women with a history of physical or sexual abuse, but sample recruitment procedures do not permit a firm generalization.”
• “Seventeen (46%) participants reported lifetime suicidal thoughts; 5 (29%) of them were born with ambiguous external genitals. However, the impact of presence of ambiguous external genitals at birth was not significant. The presence of suicidal thoughts was independent of age, age at first genital surgery, and age at gonadectomy, but significantly linked to the
  presence of gonadectomy with 23% (N = 3) of persons without gonadectomy and 61% (N = 14) of persons with gonadectomy reporting suicidal thoughts.”

Schützmann K, Brinkmann L, Schacht M, Richter-Appelt H. Psychological distress, self-harming behavior, and suicidal tendencies in adults with disorders of sex development. Archives of sexual behavior. 2009;38(1):16-33. https://doi.org/10.1007/s10508-007-9241-9

2009 Schweizer et al.
46,XY Intersekse/DSD (N=7)

• All participants reported that they experienced psychological problems and distressing feelings in response to the unexpected virilizing of their bodies during puberty. Anne, Barbara, and Gina explicitly remembered worrying about stability of their gender identity and gender role. Anne had experienced “irritations about my gender role,” Barbara remembered “doubts about my identity as a girl,” and Gina went through “identity problems due to being seen as a man by others.” Claudia wrote that she was unhappy about her male appearance. Fiona reported thoughts of suicide due to the discrepancy between her assigned gender and outer appearance. Anne, Barbara, and Daniela reported problems of social withdrawal. In addition, Daniela described feelings of shame and being “an outsider.” Anne recalled loneliness and helplessness. Anne and Daniela had also experienced increased insecurity. Emily described that she had developed depression and eating disorders during her youth.

Schweizer K, Brunner F, Schützmann K, Schönbucher V, Richter-Appelt H. Gender identity and coping in female 46, XY adults with androgen biosynthesis deficiency (intersexuality/DSD). Journal of Counseling Psychology. 2009;56(1):189-201.

2009 Wisniewski & Mazur (Review)
46,XY DSD

• Androgen Insensitivity Syndrome, 5α-Reductase-2 Deficiency, and 17β-Hydroxysteroid Dehydrogenase Deficiency
• “…self-harming behavior, and suicidal tendencies are prevalent in some samples of women with CAIS recruited from physicians or support groups”
• “Self-reported psychological distress as determined by responses to the BSI, selfharming behavior, suicidal tendencies, and suicidal attempts is observed in people affected by PAIS—whether reared male or female [12–14]. In a long-term followup study of adults with PAIS, psychological counseling for problems such as difficulty with family members, depression, and substance abuse was commonly reported during interviews—once again regardless of male or female rearing[35].”
• “A study of 15 adults reared male found that none had ever engaged in penile-vaginal intercourse and all experienced severe sexual dysfunction [41].”
• Medicalization: “It is important to focus on QoL factors for persons with a DSD diagnosis because parents ask questions such as How will my child perform in school? Will my child establish friendships? Will my child have a career? Will my child fall in love? Parents also want to know how their children will feel about their DSD diagnosis. In short, parents want information about their affected child’s future QoL.”
• More medicalization: “In conditions in which GI/R does not always develop in concordance with sex of rearing—such as PAIS, 5α-RD-2 deficiency, and 17β-HSD-3 deficiency—a better understanding of factors that influence QoL may help to explain the developmental trajectory of GI/R in people for whom GI/R development does not match their initial gender assignment”

Wisniewski AB, Mazur T. 46, XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen Insensitivity Syndrome, 5-Reductase-2 Deficiency, or 17beta-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life Outcomes. International journal of pediatric endocrinology. 2009;2009. https://doi.org/10.1155/2009/567430

2011 Bach et al.
MRKH (N=80)

• Eleven of 80 patients had undergone surgery in the past; six of these 80 women had received dilator training elsewhere, and four were sexually active. Sixty-three of 80 patients had not undergone any previous treatment. Seventeen were having satisfactory sexual intercourse, 16 were having unsatisfactory sexual intercourse, and 26 had never been sexually active; for four women, no information had been recorded. A total of 32 patients underwent vaginal dilator treatment, and 25 completed the therapy.

Bach F, Glanville JM, Balen AH. An observational study of women with müllerian agenesis and their need for vaginal dilator therapy. Fertility and Sterility. 2011;96(2):483-486. https://doi.org/10.1016/j.fertnstert.2011.05.060

2011 Liao et al.
MRKH (N=58)

• Participants reported better overall physical health and poorer overall mental health compared with normative data. Anxiety levels were higher, especially for women who had undergone vaginal treatment. Sexual wellness and function scores were poor.

Liao L-M, Conway GS, Ismail-Pratt I, Bikoo M, Creighton SM. Emotional and sexual wellness and quality of life in women with Rokitansky syndrome. American Journal of Obstetrics and Gynecology. 2011;205(2):117. e111-117. e116. https://doi.org/10.1016/j.ajog.2011.03.013

2011 Bojesen et al.
Klinefelter Syndroom (N=204)

• KS is associated with increased morbidity resulting in loss of 2-5 years in lifespan with increased mortality from different diseases and a poor socioeconomic profile.

Bojesen A, Stochholm K, Juul S, Gravholt CH. Socioeconomic trajectories affect mortality in Klinefelter syndrome. Journal of Clinical Endocrinology & Metabolism. 2011;96(7):2098-2104. https://doi.org/10.1210/jc.2011-0367

Chang S, Skakkebæk A, Gravholt CH. Klinefelter Syndrome and medical treatment: hypogonadism and beyond. Hormones (Athens, Greece). 2016. https://doi.org/10.14310/horm.2002.1622

2012 Schönbucher et al.
46, XY DSD (N=47)

2013 Van Lisdonk
Intersex/DSD (N=7)

• “Those interviewees who were aware of their condition at a young age all found that their condition had an impact during their school years. Most of them withdrew for a while, were afraid to be open towards others, adapted their behaviour and felt different or lonely. This resulted in a negative experience of school, reduced social interaction with classmates and anxiety about being bullied.”
• “In chapters 3 and 4 we have shown that intersex/dsd not only has physical consequences, but can also impact on personal experiences and social interaction with others. The interviewees with intersex/dsd do not find it easy to be open towards others about their condition. They often think carefully about who they open up to and what they tell them. They also adapt their behaviour or avoid certain situations so that their condition remains hidden. Intersex/dsd can be problematic for relationship formation, a person’s self-image as a partner or the ability to fulfil the desire to have children.
  There is embarrassment and a fear of negative reactions. Those reactions stem mainly from ignorance, embarrassment and lack of understanding. Most of the persons interviewed with intersex/dsd do not really blame those in their social environment for this and almost none of them seem to associate negative reactions from others with nonacceptance or discrimination. Intersex/dsd can however cause people to feel different, lonely and not understood. This may be related to condition-specific consequences, self-acceptance or actual or expected negative reactions, and the fact that it is not always possible to share concerns among those close to them.”

van Lisdonk J. Living with Intersex/DSD: An exploratory study of the social situation of persons with intersex/dsd. The Hague, the Netherlands: Netherlands Institute for Social Research, 25 August 2014 2014. Rapport Nr. 2014-23 Nr. 978 90 377 0717 5. https://www.scp.nl/Publicaties/Alle_publicaties/Publicaties_2014/Living_with_intersex_DSD

2014 Krupp et al.
CAIS (n=11) and MRKH (n=50)

• “psychological distress might be an issue for these individuals and therefore should be considered in treatment and counselling”
• “A correlation between psychological distress and time span from first suspicion to diagnosis was found in women with MRKH”
• “Suicidal attempts were reported by 2 persons in the CAIS sample and by 4 persons in the MRKHS sample.”

Krupp K, Fliegner M, Brunner F, Brucker S, Rall K, Richter-Appelt H. Quality of life and psychological distress in women with Mayer-Rokitansky-Küster-Hauser syndrome and individuals with complete androgen insensitivity syndrome. Open Journal of Medical Psychology. 2014;3(3):212-221. https://doi.org/10.4236/ojmp.2014.33023

2014 Van Rijn et al.
Klinefelter (n=34) & Trisomy X (n=26)

2015 D’Alberton at al.
Women with 46,XY DSD (N=43)

• “About half of the women with 46,XY DSD (51%) lived with at least one parent, 21% lived alone or with housemates, and 28% had a new family (partner, husband), whereas the figure among Italian females aged 20–60 years was 56% (P = 0.000) (http://dati.istat.it).”
• “Fourteen individuals were married or living with a partner; four women were separated or widowed, and 22 [women out of 43] had never married nor lived with a partner. This information was missing for four participants.”
• “Regarding the use of psychiatric drugs, eight individuals did not respond to the question about whether they had had pharmacological therapy, whereas 11 persons declared they had (31.4%), and this percentage is higher than in the general Italian female population between 15 and 65 years (∼12%) (D.R. Potente, Italian Survey 2010–2011, National Council of Research, pers. comm.)”
• “For the psychological and behavioral aspects analyzed by ABCL, as already reported [24,25], we found that the individuals with 46,XY DSD showed borderline median scores for IS and ES. In agreement with other studies [19,20], they were also more likely to be depressed and anxious, showed more withdrawal and aggressive behavior, and had more thought and attention problems than the women in the comparison group. Assessed together, these data suggest that persons with 46,XY DSD may have higher psychological distress than the general female population.”
• “[they have] statistically higher scores than the comparison group for depression, anxiety, internalizing and externalizing problems.”

D’Alberton F, Assante MT, Foresti M, Balsamo A, Bertelloni S, Dati E, et al. Quality of Life and Psychological Adjustment of Women Living with 46, XY Differences of Sex Development. The journal of sexual medicine. 2015. https://doi.org/10.1111/jsm.12884

2015 Freriks
Turner Syndrome (N=150)

• “Twenty-three patients (mean age 38 yr) consulted the psychologist with the following reasons: need for support in accepting TS related limitations in daily life (70%), low self esteem (55%), non assertiveness (45%), lack of social support (25%), and infertility related emotional problems (10%).”
• “Our study confirms that many TS women experience difficulties in regards to acceptance of limitations related to TS and low self esteem. Remarkably, emotional problems related to infertility were mentioned by only a small minority.”

Freriks K. Turner syndrome in adulthood: a childhood disease grown up [Proefschrift]. Nijmegen: Radboud Universiteit; 2015. http://hdl.handle.net/2066/139500

2015 Fisher et al.
Klinefelter (N=46)

• In particular, 17.1% of KS obtained just the primary school degree and only 2.4% the university one (vs. 0% and 75%, respectively).
• Smoking habit was more often reported in KS (KS = 37.0% vs. HC = 11.6%)
• KS subjects reported higher SCL-90-R Positive Symptom Distress Index (PSDI), and subscale scores as follows: SCL-90 Obsession-Compulsive (O-C), and SCL-90-R Somatization (SOM).
• KS subjects showed a higher frequency of Axis I Psychiatric Disorders according to DSM-IV criteria (30.4% vs. 7.0%), which was due to a higher prevalence of Mood Disorders.
• Considering BUT, the KS group showed significantly higher uneasiness related to genitals
• Considering hypersexuality, the KS group reported significantly higher Sexual Addiction Screening Test (SAST) scores.
• When paraphilic fantasies and behaviors were assessed, KS subjects showed a higher frequency of voyeuristic fantasies […], during masturbation (52.2% vs. 25.6%).
• Despite our finding lower levels of TIQ in KS, in line with previous studies [6], 47,XXY individuals were not, on average, intellectually disabled.

Fisher AD, Castellini G, Casale H, Fanni E, Bandini E, Campone B, et al. Hypersexuality, Paraphilic Behaviors, and Gender Dysphoria in Individuals with Klinefelter’s Syndrome. The journal of sexual medicine. 2015;12(12):2413-2424. https://doi.org/10.1111/jsm.13048

2016 Jones et al.
Intersex (N=272)

• “In 2015, the “Australians born with Congenital Variations in Sex Characteristics (Intersex/DSD/ hormonal, chromosomal or other biological variations/ conditions)” anonymous survey was conducted online, gathering data on 272 people with intersex variations. Participants ranged in age from 16-85+, from all states of Australia in proportion to the broader population, and a fifth lived internationally.Only a quarter of participants rated their overall experience at school positively. The overwhelming majority of participants (92%) did not attend a school with inclusive puberty/sex education. Overall, 18% of people with intersex variations had only had a primary school education – a larger portion than the general Australian population (2%). Many participants (66%) had experienced discrimination ranging from indirect to direct verbal, physical or other discriminatory abuse. Wellbeing risks were high, as documented in the next section.A key finding of this study was that most people with intersex variations had not told school staff about their variation, whilst just over half had told their classmates. Principals were the least likely people in a student’s life to be told about their intersex variation overall; further they were the most likely to be unsupportive.”

Jones T, Hart B, Carpenter M, Ansara G, Leonard W, Lucke J. Intersex: Stories and Statistics from Australia: Open Book Publishers; 2016. ISBN: 978-1-78374-208-0, https://doi.org/10.11647/OBP.0089

UNESCO. From insult to inclusion: Asia-Pacific report on school bullying, violence and discrimination on the basis of sexual orientation and gender identity. United Nations Educational, Scientific and Cultural Organization (UNESCO), 2015. Rapport Nr. TH/DOC/HP2/15/042. http://bangkok.unesco.org/content/insult-inclusion-asia-pacific-report-school-bullying-violence-and-discrimination-basis

2017 Bennecke et al.
DSD (N=110): CAH (n=44), XY females (n=39), XY males (n=10), other (n=9)

• “In this study, nine participants (8.2%) described themselves as a gender other than male or female. They rated their HRQoL and psychological distress as similar to the rest of the cohort. This observation indicated that identification with a gender outside or overriding male or female dichotomy is not associated with impaired QoL or psychological distress.”
• “In this study, a considerable difference between psychological and physical well-being was identified in a cohort of 110 adults with various DSD conditions. Participants reported overall higher physical HRQoL, normal mental HRQoL but high psychological distress (42.7%) measured by SF-36 and BSI accordingly.”

Bennecke E, Thyen U, Grüters A, Lux A, Köhler B. Health-related quality of life and psychological well-being in adults with differences/disorders of sex development. Clinical endocrinology. 2017;86(4):634-643. https://doi.org/10.1111/cen.13296

2017 Schweizer et al.
DSD (N=69)

• The majority received medical treatment in relation to their DSD during childhood and adolescence.
• Seventy percent reported having had a best friend and 29% a confidant during childhood.
• Sixty-one percent showed clinically relevant psychological distress,
• 45% reported suicidal thoughts at least at one point in their lives.
• Quality of parental care and having had a best friend correlated positively with adult outcome, whereas treatment experiences correlated with aspects of impaired adjustment.

Schweizer K, Brunner F, Gedrose B, Handford C, Richter-Appelt H. Coping With Diverse Sex Development: Treatment Experiences and Psychosocial Support During Childhood and Adolescence and Adult Well-Being. Journal of Pediatric Psychology. 2017;42(5):504-519. https://doi.org/10.1093/jpepsy/jsw058

2018 Falhammar et al.
Turner (n=301), Klinefelter (n=224), XY-DSD (n=222), XX-DSD (excluding congenital adrenal hyperplasia (CAH) and 46,XX males)(n=21), 46,XX-CAH (n=226), and 45,X/46,XY (n=45)

2018 Kreukels et al.
Turner (n=325), Klinefelter (n=219), XY-DSD women with androgen effect (n=107), XY-DSD women without androgen effect (n=63), XY-DSD men (n=87), 46,XX women CAH (n=221)

• Gender changes were reported by 5% of participants,
• Only in 1% did the gender change take place after puberty and was likely initiated by the patient.
• With with Klinefelter and Turner syndromes excluded, genderchange was reported in 12%, (2% after puberty).
• 39 participants (4%) reported gender variance: between male and female, a gender other than male or female, or gender queer, alternating gender roles,
  or a gender expression that differed from the reported gender. This group had lower self-esteem and more anxiety and depression than the other participants.

Data: Kreukels et al. 2018

Kreukels BPC, Köhler B, Nordenström A, Roehle R, Thyen U, Bouvattier C, et al. Gender Dysphoria and Gender Change in Disorders of Sex Development/Intersex Conditions: Results From the dsd-LIFE Study. The Journal of Sexual Medicine. 2018;15(5):777-85. https://doi.org/10.1016/j.jsxm.2018.02.021

2018 Khorased et al.
CAH (n=22), 5α-RD-2 (n=20), CAIS (n=19)

• All participants were female-assigned at birth. Ten patients (16.4%) transitioned to the male gender.
• Overall, 68% of patients had one or more lifetime Axis I disorders, including 63.6% of the CAH participants, 90% of 5α-RD-2 participants, and 52.6% of the CAIS participants.
• The most commonly observed were affective disorders (27.9%), gender identity disorder (27.9%), and anxiety (16.4%).
• This might be due to the fact that patients with DSD conditions are mostly treated medically and their mental health is often superficially addressed in developing countries such as Iran, at least in the past.

Khorashad BS, Aghili Z, Kreukels BPC, Reid AG, Roshan GM, Hiradfar M, et al. Mental Health and Disorders of Sex Development/Intersex Conditions in Iranian Culture: Congenital Adrenal Hyperplasia, 5-α Reductase Deficiency-Type 2, and Complete Androgen Insensitivity Syndrome. Archives of sexual behavior. 2018. https://doi.org/10.1007/s10508-017-1139-6