Consensus statement on management of intersex disorders

Archives of Disease in Childhood

Volumn 91, Issue 7, 2006, Pages 554-563

  Hughes, Ieuan A ^a   Houk, C ^b   Ahmed, S F ^b   Lee, P A ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

SEX HORMONE; TESTOSTERONE;

CLINICAL ASSESSMENT; CONSENSUS; CULTURAL FACTOR; GENDER IDENTITY; GONAD TUMOR; HERMAPHRODITISM; HORMONE SUBSTITUTION; HUMAN; HYPOGONADISM; MEDICAL PRACTICE; MOLECULAR GENETICS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PSYCHOSOCIAL CARE; REVIEW; SEXUAL DEVELOPMENT; SOCIAL ASPECT; SURGERY;

CULTURE; FEMALE; GENDER IDENTITY; GONADAL STEROID HORMONES; HERMAPHRODITISM; HUMANS; MALE; PATIENT CARE TEAM; PROGNOSIS; PSYCHOTHERAPY; STEREOTYPING; TERMINOLOGY;

EID: 33745773870     PISSN: 00039888     EISSN: 14682044     Source Type: Journal    
DOI: 10.1136/adc.2006.098319     Document Type: Review

References (92)

1. Frader J, Alderson P, Asch A, et al. Health care professionals and intersex conditions. Arch Pediatr Adolesc Med 2004;158:426-9.
2. Conn J, Gillam L, Conway G. Revealing the diagnosis of androgen insensitivity syndrome in adulthood. BMJ 2005;331:628-30.
3. Dreger AD, Chase C, Sousa A, et al. Changing the nomenclature/taxonomy for intersex: A scientific and clinical rationale. J Pediatr Endocrinol Metab 2005;18:729-33.
4. Brown J, Warne G. Practical management of the intersex infant. J Pediatr Endocrinol Metab 2005;18:3-23.
5. Cohen-Kettenis PT. Gender change in 46,XY persons with 5-alpha-reductase-2 deficiency and 17-beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav 2005;34:399-410.
6. Meyer-Bahlburg HF. Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Arch Sex Behav 2005;34:423-38.
7. Zucker KJ. Intersexuality and gender identity differentiation. Annu Rev Sex Res 1999;10:1-69.
8. Cohen-Bendahan CCC, van de Beek C, Berenbaum SA. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings. Neurosci Biobehav Rev 2005;29:353-384.
9. Meyer-Bahlburg HF. Gender and sexuality in congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001;30:155-71.
10. Nordenström A, Servin A, Bohlin G, et al. Sex-typed toy play behavior correlates with the degree of prenatal androgen exposure assessed by CYP21 genotype in girls with congenital adrenal hyperplasia. J Clin Endo Metab 2002;87:5119-24.
11. Goy RW, Bercovitch FB, McBrair MC. Behavioral masculinization is independent of genital masculinization in prenatally androgenized female rhesus macaques. Horm Behav 1988;22:552-71.
12. Wallen K. Hormonal influences on sexually differentiated behavior in nonhuman primates. Front Neuroendocrinol 2005;26:7-26.
13. Moore CL. The role of maternal stimulation in the development of sexual behavior and its neural basis. Ann NY Acad Sci 1992;662:160-77.
14. Wallen K. Nature needs nurture: the interaction of hormonal and social influences on the development of behavioral sex differences in rhesus monkeys. Horm Behav 1996;30:364-78.
15. De Vries GJ, Rissman EF, Simerly RB, et al. A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. J Neurosci 2002;22:9005-14.
16. Skuse DH, James RS, Bishop DVM, et al. Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function. Nature 1997;387:705-8.
17. Hines M, Ahmed F, Hughes IA. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Arch Sex Behav 2003;32:93-101.
18. Arnold AP, Rissman EF, De Vries GJ. Two perspectives on the origin of sex differences in the brain. Ann NY Acad Sci 2003;1007:176-88.
19. Luders E, Narr K, Thompson PM, et al. Gender differences in cortical complexity. Nature Neurosci 2004;7:799-800.
20. Paus T. Mapping brain maturation and cognitive development during adolescence. Trends Cogn Sci 2005;9:60-8.
21. Consortium on the Management of Disorders of Sex Differentiation. Clinical guidelines: for the management of disorders of sex development in childhood. 2006 (www.dsdguidelines.org).
22. Lee PA. A perspective on the approach to the intersex child born with genital ambiguity. J Pediatr Endocrinol Metab 2004;17:133-40.
23. American Academy of Pediatrics. Council on Children with Disabilities. Care coordination in the medical home: integrating health and related systems of care for children with special health care needs, Pediatrics 2005;116:1238-44.
24. Cashman S, Reidy P, Cody K, et al. Developing and measuring progress toward collaborative, integrated, interdisciplinary health teams. J Interprof Care 2004;18:183-96.
25. Warne G. Support groups for CAH and AIS. Endocrinologist 2003;13:175-8.
26. Feldman KW, Smith DW. Fetal phallic growth and penile standards for newborn male infants. J Pediatr 1975;86:395-8.
27. Schonfield WA, Beebe GW. Normal growth and variation in the male genitalia from birth to maturity. J Urol 1942;48:759-77.
28. Fujieda K, Matsuura N. Growth and maturation in the male genitalia from birth to adolescence. II Change of penile length. Acta Paediatr Japan 1987;29:220-3.
29. Tuladhar R, Davis PG, Batch J, et al. Establishment of a normal range of penile length in preterm infants. J Paediatr Child Health 1998;34:471-3.
30. Cheng PK, Chanoine JP. Should the definition of micropenis vary according to ethnicity? Horm Res 2001;55:278-81.
31. Zachmann M, Prader A, Kind HP, et al. Testicular volume during adolescence: cross-sectional and longitudinal studies. Helv Paediatr Acta 1974;29:61-72.
32. Oberfield SE, Mondok A, Shahrivar F, et al. Clitoral size in full-term infants. Am J Perinatol 1989;6:453-54.
33. Verkauf BS, Von Thron J, O'Brien WF. Clitoral size in normal women. Obstet Gynecol 1992;80:41-4.
34. Lloyd J, Crouch NS, Minto CL, et al. Female genital appearance: "normality" unfolds. BJOG 2005;112:643-6.
35. Grumbach MM, Hughes IA, Conte FA. Disorders of sex differentiation. In:Larsen PR, Kronenberg HM, Melmed S, et al, editors. Williams textbook of endocrinology, 10th edition. Philadelphia: WB Saunders, 2003:842-1002.
36. Ahmed SF, Cheng A, Dovey L, et al. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab 2000;85:658-65.
37. Morel Y, Rey R, Teinturier C, et al. Aetiological diagnosis of male sex ambiguity: a collaborative study. Eur J Pediatr 2002;161:49-59.
38. Ogilvy-Stuart AL, Brain CE. Early assessment of ambiguous genitalia. Arch Dis Child 2004;89:401-7.
39. Quillin JM, Jackson-Cook C, Bodurtha J. The link between providers and patients: how laboratories can ensure quality results with genetic testing. Clin Leadership Manag Rev 2003;17:351-7.
40. Pagon RA, Tarczy-Hornoch P, Baskin PK, et al. GeneTests-Gene Clinics: genetic testing information for a growing audience. Hum Mut 2002;19:501-9.
41. Dessens AB, Slijper FM, Drop SL. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav 2005;32:389-97.
42. Mazur T. Gender dysphoria and gender change in androgen insensitivity or micropenis. Arch Sex Behav, 2005;34:411-21.
43. Clayton PE, Miller WL, Oberfield SE, Ritzen EM, Speisser PW, ESPE/LWPES CAH Working Group. Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. Horm Res 2002;58:188-95.
44. Nicolino M, Bendelac N, Jay N, et al. Clinical and biological assessments of the undervirilized male. BJU Int 2004;93(suppl 3):20-5.
45. Mendonca BB, Inacio M, Costa EMF, et al. Male pseudohermaphroditism due to 5 alpha-reductase 2 deficiency: outcome of a Brazilian Cohort. Endocrinologist 2003;13:202-4.
46. Migeon CJ, Wisniewski AB, Gearhart JP, et al. Ambiguous genitalia with perineoscrotal hypospadias in 46,XY individuals: long-term medical, surgical, and psychosexual outcome. Pediatrics 2002;110:e31.
47. Lee PA, Witchel SF. Genital surgery among females with congenital adrenal hyperplasias: Changes over the past five decades. J Pediatr Endocrinol Metab 2002;15:1473-7.
48. Rink RC, Adams MC. Feminizing genitoplasty: state of the art. World J Urol 1998;16:212-18.
49. Farkas A, Chertin B, Hadas-Halpren I. 1-Stage feminizing genitoplasty: 8 years of experience with 49 cases. J Urol 2001;165:2341-6.
50. Baskin LS. Anatomical studies of the female genitalia: surgical reconstructive implications. J Pediatr Endocrinol Metab 2004;17:581-7.
51. Crouch NS, Minto CL, Laio LM, et al. Genital sensation after feminizing genitoplasty for congenital adrenal hyperplasia: a pilot study. BJU Int 2004;93:135-8.
52. Meyer-Bahlburg HF, Migeon CJ, Berkovitz GD, et al. Attitudes of adult 46,XY intersex persons to clinical management policies. J Urol 2004;171:1615-19.
53. American Academy of Pediatrics. Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anaesthesia. Pediatrics 1996;97:590-4.
54. Eroglu E, Tekant G, Gundogdu G, et al. Feminizing surgical management of intersex patients. Pediatr Surg Int 2004;20:543-7.
55. Alizai N, Thomas DFM, Lilford RJ, et al. Feminizing genitoplasty for congenital adrenal hyperplasia: what happens at puberty? J Urol 1999;161:1588-91.
56. Bailez MM, Gearhart JP, Migeon CG, et al. Vaginal reconstruction after initial construction of the external genitalia in girls with salt wasting adrenal hyperplasia. J Urol 1992;148:680-4.
57. Mouriquand PD, Mure PY. Current concepts in hypospadiology. BJU Int 2004;93(suppl 3):26-34.
58. Bettocchi C, Ralph DJ, Pryor JP. Pedicled phalloplasty in females with gender dysphoria. BJU Int 2005;95:120-4.
59. Hurt WG, Bodurtha JN, McCall JB, et al. Seminoma in pubertal patient with androgen insensitivity syndrome. Am J Obstet Gynecol 1989;161:530-1.
60. Rorth M, Rajpert-De Meyts E, Andersson L, et al. Carcinoma in situ in the testis. Scand J Urol Nephrol Suppl 2000;205:106-86.
61. Nihoul-Fékété C. The Isabel Forshall Lecture. Surgical management of the intersex patient: an overview in 2003, J Pediatr Surg 2004;39:144-5.
62. Warne GL, Grover S, Zajac JD. Hormonal therapies for individuals with intersex conditions: protocol for use. Treat Endocrinol 2005;4:19-29.
63. Rogol AD. New facets of androgen replacement therapy during childhood and adolescence. Expert Opin Pharmacother 2005;6:1319-36.
64. Ahmed SF, Tucker P, Mayo A, et al. Randomized, crossover comparison study of the short-term effect of oral testosterone undecanoate and intramuscular testosterone depot on linear growth and serum bone alkaline phosphatase. J Pediatr Endocrinol Metab 2004;17:941-50.
65. Mayo A, Macintyre H, Wallace AM, et al. Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover. J Clin Endocrinol Metab 2004;89:681-7.
66. Weidemann W, Peters B, Romalo G, et al. Response to androgen treatment in a patient with partial androgen insensitivity and a mutation in the deoxyribonucleic acid binding domain of the androgen receptor. J Clin Endocrinol Metab 2000;83:1173-81.
67. Kazak AE, Cant MC, Jensen MM, et al. Identifying psychosocial risk indicative of subsequent resource use in families of newly diagnosed pediatric oncology patients. J Clin Oncol 2003;21:3220-5.
68. Martin CL, Ruble DN, Szkrybalo J. Cognitive theories of early gender development. Psychol Bull 2002;128:903-33.
69. Zucker KJ. Measurement of psychosexual differentiation. Arch Sex Behav 2005;34:375-88.
70. Carmichael P, Ransley P. Telling children about a physical intersex condition. Dialogues Pediatr Urol 2002;25:7-8.
71. Committee on Paediatric AIDS, American Academy of Pediatrics. Disclosure of illness status to children and adolescents with HIV infection. Pediatrics 1999;103:164-6.
72. Money J. Sex errors of the body and related syndromes: a guide to counselling children, adolescents, and their families, 2nd edition. Baltimore: Paul H Brookes Publishing Co, 1994.
73. Basson R, Leiblum S, Brotto L, et al. Definitions of women's sexual dysfunction reconsidered: advocating expansion and revision. J Psychosom Obstet Gynecol 2003;24:221-9.
74. Creighton S, Alderson J, Brown S, Minto CL. Medical photography: ethics, consent and the intersex patient. BJU Int 2002;89:67-71.
75. Ursano RJ, Bell C, Eth S, et al. Work Group on ASD and PTSD; Steering Committee on Practice Guidelines. Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161(11 suppl):3-31.
76. Kuhnle U, Bullinger M. Outcome of congenital adrenal hyperplasia. Pediatr Surg Int 1997;12:511-15.
77. Warne G, Grover S, Hutson J, et al. Murdoch Childrens Research Institute Sex Study Group. A long-term outcome study of intersex conditions. J Pediatr Endocrinol Metab 2005;18:555-67.
78. Creighton SM. Long-term outcome of feminization surgery: the London experience. BJU Int 2004;93(suppl 3):44-6.
79. Steiner E, Woernie F. Carcinoma of the neovagina: case report and review of the literature. Gynecol Oncol 2002;84:171-5.
80. Schober JM. Long-term outcomes of feminizing genitoplasty for intersex. In: Pediatric surgery and urology: long-term outcomes. London: WB Saunders Co (in press).
81. Wisniewski AB, Migeon G, Meyer-Bahlburg HF, et al. Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. J Clin Endocrinol Metab 2000;85:2664-9.
82. Honecker F, Stoop H, de Krijger RR, et al. Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells. J Pathol 2004;203:849-57.
83. Cools M, Van Aerde K, Kersemaekers AM, et al. Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes. J Clin Endocrinol Metab 2005;90:5295-303.
84. Cools M, Honecker F, Stoop H, et al. Maturation delay of germ cells in trisomy 21 fetuses results in increased risk for the development of testicular germ cell tumors. Hum Pathol 2006;37:101-11.
85. Ramani P, Yeung CK, Habeebu SS. Testicular intratubular germ cell neoplasia in children and adults with intersex. Am J Surg Pathol 1993;17:1124-33.
86. Hannema SE, Scott IS, Rajperts-De Meyts E, et al. Testicular development in the complete androgen insensitivity syndrome. J Pathol 2006;208:518-27.
87. Warne GL, Bhatia V. Intersex, East and West. In:Sytsma S, editor. Ethics and intersex. Berlin: Springer, 2000:183-205.
88. Achermann JC, Ozisik G, Meeks JJ, et al. Genetic causes of human reproductive disease. J Clin Endocrinol Metab 2002;87:2447-54.
89. Small CL, Shima JE, Uzumcu M, et al. Profiling gene expression during the differentiation and development of the murine embryonic gonad. Biol Reprod 2005;72:492-501.
90. Martin PL. Moving toward an international standard in informed consent: the impact of intersexuality and the internet on the standard of care. Duke J Gend Law Policy 2002;9:135-69.
91. Department of Health. Reference guide to consent for examination or treatment. London, DoH, 2001 (www.doh.gov.uk/consent).
92. Sentencia SU-337/99, May 12, 1999; T-551/99, Aug 2 1999.