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Eur J Pediatr Surg 2009; 19(4): 203-210
DOI: 10.1055/s-0029-1233490
Review

© Georg Thieme Verlag KG Stuttgart · New York

Congenital Adrenal Hyperplasia: A Critical Appraisal of the Evolution of Feminizing Genitoplasty and the Controversies Surrounding Gender Reassignment

L. H. Braga1 , J. L. Pippi Salle2
  • 1McMaster Children's Hospital, McMaster University, Urology, Hamilton, Canada
  • 2The Hospital for Sick Children, Urology, Toronto, Canada
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Publication History

received June 15, 2009 accepted after revision June 26, 2009

Publication Date:
19 August 2009 (online)

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Abstract

Although congenital adrenal hyperplasia (CAH) is the most common cause of genital ambiguity, its surgical treatment remains controversial and often times difficult, especially in cases of high urethro-vaginal confluence. Many aspects are still uncertain, such as the timing of feminizing genitoplasty and type of surgical technique. The objective of this study is to provide a thorough review of the surgical management of children with CAH, discussing the evolution of feminizing genitoplasty and its different techniques, and also to critically appraise the available literature on the timing of surgical intervention and gender reassignment. Prospective long-term studies evaluating the results of modern feminizing genitoplasty techniques are needed as current evidence is based on outdated operations that are no longer used. To date, there have been no studies comparing early and delayed feminizing genitoplasty with regard to psychological outcomes. All families should be counseled regarding the controversies and treatment options, including the watchful waiting approach.

Key words

congenital adrenal hyperplasia - ambiguous genitalia - feminizing genitoplasty - urogenital sinus - gender reassignment

References

  • 1 Miller WL. Genetics, diagnosis, and management of 21-hydroxilase deficiency.  J Clin Endocrinol Metab. 1994;  78 241-246
    Google Scholar
  • 2 Speiser PW, White PC. Congenital adrenal hyperplasia.  N Engl J Med. 2003;  349 776-788
    Google Scholar
  • 3 Merke DP, Bornstein SR. Congenital adrenal hyperplasia.  Lancet. 2005;  365 2125-2136
    Google Scholar
  • 4 White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxilase deficiency.  Endocr Rev. 2000;  21 245-291
    Google Scholar
  • 5 Warne GL, Zajac JD. Disorders of sexual differentiation.  Endocrinol Metab Clin North Am. 1998;  4 945-966
    Google Scholar
  • 6 New MI, Carlson A, Obeid J. et al . Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.  J Clin Endocrinol Metab. 2001;  86 5651-5657
    Google Scholar
  • 7 Prader A. Der Genitalbefund beim Pseudohermphroditismus feminus des kongenitalen adrenogenitalen Syndroms: Morphologie, Häufigkeit, Entwicklung und Vererbung der verscheidenen Genitalformen.  Helv Pediatr Acta. 1954;  9 231-248
    Google Scholar
  • 8 Schnitzer JJ. Surgical treatment of congenital adrenal hyperplasia.  Endocrinol Metab Clin North Am. 2001;  30 121-135
    Google Scholar
  • 9 Clayton PE, Miller WL, Oberfield SE. et al . Consensus statement on 21-hydroxilase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology.  J Clin Endrinol Metab. 2002;  87 408-453
    Google Scholar
  • 10 Rink RC, Adams MC. Feminizing genitoplasty: state of art.  World J Urol. 1998;  16 212-218
    Google Scholar
  • 11 Bachega TASS, Madureira G, Brenlha EML. et al . Tratamento da hiperplasia supra-renal congênita por deficiência da 21-hidroxilase.  Arq Bras Endocrinol Metab. 2001;  45 64-72
    Google Scholar
  • 12 Diamond M, Sigmundson HK. Management of intersexuality: guidelines for dealing with persons with ambiguous genitalia.  Arch Pediatr Adolesc Med. 1997;  151 1046-1050
    Google Scholar
  • 13 Creighton SM. Feminizing genital surgery: what should be done and when?.  J Pediatr Adolesc Gynecol. 2005;  18 63-69
    Google Scholar
  • 14 Hendren WH, Donahoe PK. Correction of congenital abnormalities of the vagina and perineum.  J Pediatr Surg. 1980;  15 751-763
    Google Scholar
  • 15 Snyder  III  HM, Retik AB, Bauer SB, Colodny AH. Feminizing genitoplasty: a synthesis.  J Urol. 1983;  129 1024-1026
    Google Scholar
  • 16 Donahoe PK, Gustafson ML. Early one-stage surgical reconstruction of the extremely high vagina in patients with congenital adrenal hyperplasia.  J Pediatr Surg. 1994;  29 352-358
    Google Scholar
  • 17 Young, Young H.. 1937 .Genital Abnormalities, Hermaphroditism and Related Adrenal Diseases. Baltimore: Williams & Wilkins 1937
  • 18 Hampson JG. Hermaphroditic genital appearance, rearing and eroticism in hyperadrenocorticism.  Bull Johns Hopkins Hosp. 1955;  96 265-273
    Google Scholar
  • 19 Gross RE, Randolph J, Crigler  Jr  JF. Clitorectomy for sexual abnormalities: indications and technique.  Surgery. 1966;  59 300-308
    Google Scholar
  • 20 Sircilli MHP, Mendonça BB, Denes FT. et al . Anatomical and functional outcomes of feminizing genitoplasty for ambiguous genitalia in patients with virilizing congenital adrenal hyperplasia.  Clinics. 2006;  61 209-214
    Google Scholar
  • 21 Minto CL, Liao LM, Woodhouse CRJ. et al . The effect of clitoral surgery on sexual outcome in individuals who have intersex conditions with ambiguous genitalia: a cross-sectional study.  Lancet. 2003;  361 1252-1257
    Google Scholar
  • 22 Lattimer JK. Relocation and recession of the enlarged clitoris with preservation of the glans: an alternative to amputation.  J Urol. 1961;  86 113-116
    Google Scholar
  • 23 Newman K, Randolph J, Anderson K. The surgical management of infants and children with ambiguous genitalia.  Ann Surg. 1992;  215 645-653
    Google Scholar
  • 24 Schmid M. Plastische Korrektur der äußeren Genitale bei einem männlichen Scheinzwitter.  Langenbecks Arch Klin Chir. 1961;  298 977
    Google Scholar
  • 25 Shaw A. Subcutaneous reduction clitoroplasty.  J Pediatr Surg. 1977;  12 331-338
    Google Scholar
  • 26 Barrett TM, Gonzales  Jr  ET. Reconstruction of the female external genitalia.  Urol Clin North Am. 1980;  7 455-463
    Google Scholar
  • 27 Glassberg KI, Laungani G. Reduction clitoroplasty.  Urology. 1981;  17 604-605
    Google Scholar
  • 28 Mollard P, Juskiewenski S, Sarkissian J. Clitoroplasty in intersex: a new technique.  Br J Urol. 1981;  53 371-373
    Google Scholar
  • 29 Rajfer J, Ehrlich RM, Goodwin WE. Reduction clitoroplasty via ventral approach.  J Urol. 1982;  128 341-343
    Google Scholar
  • 30 Kogan SJ, Smey P, Levitt SB. Subtunical total reduction clitoroplasty: a safe modification of existing techniques.  J Urol. 1983;  130 746-748
    Google Scholar
  • 31 Gearhart JP, Burnett A, Owen JH. Measurment of pudendal evoked potentials during feminizing genitoplasty: technique and applications.  J Urol. 1995;  153 486-487
    Google Scholar
  • 32 Baskin LS, Erol A, Li YW. et al . Anatomical studies of the human clitoris.  J Urol. 1999;  162 1015-1020
    Google Scholar
  • 33 Yang J, Felsen D, Poppas DP. Nerve sparing ventral clitoroplasty: analysis of clitoral sensivity and viability.  J Urol. 2007;  178 1598-1601
    Google Scholar
  • 34 Poppas DP, Hochsztein AA, Baergen RN. et al . Nerve sparing ventral clitoroplasty preserves dorsal nerves in congenital adrenal hyperplasia.  J Urol. 2007;  178 1802-1806
    Google Scholar
  • 35 Braga LH, Lorenzo AJ, Tatsuo ES. et al . Prospective evaluation of feminizing genitoplasty using partial urogenital sinus mobilization for congenital adrenal hyperplasia.  J Urol. 2006;  176 2199-2204
    Google Scholar
  • 36 Pippi Salle JL, Braga LH, Macedo N. et al . Corporeal sparing dismembered clitoroplasty: an alternative technique for feminizing genitoplasty.  J Urol. 2007;  178 1796-1801
    Google Scholar
  • 37 Farkas A, Chertin B, Hadas-Halpren I. 1-stage feminizing genitoplasty: 8 years of experience with 49 cases.  J Urol. 2001;  165 2341-2346
    Google Scholar
  • 38 Farkas A, Chertin B. Feminizing genitoplasty in patients with 46XX congenital adrenal hyperplasia.  J Pediatr Endocrinol Metab. 2001;  14 713-722
    Google Scholar
  • 39 Jones HW, Jones GES. The gynecological aspects of adrenal hyperplasia and allied disorders.  Am J Obstet Gynecol. 1954;  68 1330-1365
    Google Scholar
  • 40 Fortunoff S, Lattimer JK, Edson M. Vaginoplasty technique for female pseudohermaphrodites.  Surg Gynecol Obstet. 1964;  118 545-548
    Google Scholar
  • 41 Freitas-Filho L, Carnevale J, Melo CE. et al . A posterior-based omega-shaped flap vaginoplasty in girls with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.  BJU Int. 2003;  91 263-264
    Google Scholar
  • 42 Hendren WH, Crawford JD. Adrenogenital syndrome: the anatomy of the anomaly and its repair.  J Pediatr Surg. 1969;  4 49-58
    Google Scholar
  • 43 Passerini-Glazel G. A new 1-stage procedure for clitorovaginoplasty in severely masculinized female pseudohermaphrodites.  J Urol. 1989;  142 565-568
    Google Scholar
  • 44 De Jong TPVM, Boemers TML. Neonatal management of female intersex by clitorovaginoplasty.  J Urol. 1995;  154 830-832
    Google Scholar
  • 45 Gonzalez R, Fernandes ET. Single-stage feminization genitoplasty.  J Urol. 1990;  143 776-778
    Google Scholar
  • 46 Powell DM, Newman KD, Randolph J. A proposed classification of vaginal anomalies and their surgical correction.  J Pediatr Surg. 1995;  30 271-276
    Google Scholar
  • 47 Peña A. Total urogenital mobilization – an easier way to repair cloacas.  J Pediatr Surg. 1997;  32 263-268
    Google Scholar
  • 48 Rink RC, Pope JC, Kropp BP. et al . Reconstruction of the high urogenital sinus: early perineal prone approach without division of the rectum.  J Urol. 1997;  158 1293-1297
    Google Scholar
  • 49 Di Benedetto V, Gioviale M, Bagnara V. et al . The anterior sagittal transanorectal approach: a modified approach to 1-stage clitoral vaginoplasty in severely masculinized female pseudohermaphrodites — preliminary results.  J Urol. 1997;  157 330-332
    Google Scholar
  • 50 Dòmini R, Rossi F, Ceccarelli PL. et al . Anterior sagittal transanorectal approach to the urogenital sinus in adrenogenital syndrome: preliminary report.  J Pediatr Surg. 1997;  32 714-716
    Google Scholar
  • 51 Rink RC, Adams MC, Misseri R. A new classification for genital ambiguity and urogenital sinus anomalies.  BJU Int. 2005;  95 638-642
    Google Scholar
  • 52 Ludwikowski B, Hayward IO, Gonzalez R. Total urogenital sinus mobilization: expanded applications.  BJU Int. 1999;  83 820-822
    Google Scholar
  • 53 Jenak R, Ludwikowski B, Gonzalez R. Total urogenital sinus mobilization: a modified perineal approach for feminizing genitoplasty and urogenital sinus repair.  J Urol. 2001;  165 2347-2349
    Google Scholar
  • 54 Ganesan A, Smith GHH, Broome K. et al . Congenital adrenal hyperplasia: preliminary observations of the urethra in 9 cases.  J Urol. 2002;  167 275-279
    Google Scholar
  • 55 Braga LH, Silva IN, Tatsuo ES. Total urogenital sinus mobilization in the repair of ambiguous genitalia in children with congenital adrenal hyperplasia.  Arq Bras Endocrinol Metabol. 2005;  49 908-915
    Google Scholar
  • 56 Rink RC, Metcalfe PD, Cain MP. et al . Use of the mobilized sinus with total urogenital mobilization.  J Urol. 2006;  176 2205-2211
    Google Scholar
  • 57 Rink R, Kaefer M. Surgical management of intersexuality, cloacal, malformation, and other abnormalities of the genitalia in girls. In: Kavoussi LR, Novick AC, Partin AW, Wein CA, editors. Campbell – Walsh Urology. 9th ed. Philadelphia: Saunder-Elsevier 2007 pp 3830-3869
  • 58 Rink RC, Metcalfe P, Cain M. et al . Partial urogenital mobilization: the advantages without the risks.  J Pediatr Urol. 2005;  1 232-233
    Google Scholar
  • 59 Rink RC, Metcalfe PD, Kaefer MA. et al . Partial urogenital mobilization: a limited proximal dissection.  J Pediatr Urol. 2006;  2 351-356
    Google Scholar
  • 60 Leslie JA, Cain MP, Rink RC. Feminizing genital reconstruction in congenital adrenal hyperplasia.  Indian J Urol. 2009;  25 17-26
    Google Scholar
  • 61 Creighton SM, Minto CL, Steele SJ. Objective cosmetic and anatomical outcomes at adolescence of feminizing surgery for ambiguous genitalia done in childhood [letter].  Lancet. 2001;  358 124-125
    Google Scholar
  • 62 Hanza AF, Soliman HA, Abdel Hay SA. et al . Total urogenital sinus mobilization in the repair of cloacal anomalies and congenital adrenal hyperplasia.  J Pediatr Surg. 2001;  36 1656-1658
    Google Scholar
  • 63 Gozalbez R, Castellan M, Ibrahim E. et al . New concepts in feminizing genitoplasty – is the Fortunoff flap obsolete?.  J Urol. 2005;  174 2350-2353
    Google Scholar
  • 64 Roll MF, Kneppo C, Roth H. et al . Feminizing genitoplasty: one-stage genital reconstruction in congenital adrenal hyperplasia: 30 years’ experience.  Eur J Pediatr Surg. 2006;  16 329-333
    Google Scholar
  • 65 Savanelli A, Alicchio F, Esposito C. et al . A modified approach for feminizing genitoplasty.  World J Urol. 2008;  26 517-520
    Google Scholar
  • 66 Farhat WA. Early intervention of CAH surgical management.  J Pediatr Adolesc Gynecol. 2005;  18 66-69
    Google Scholar
  • 67 Passerini-Glazel G. Feminizing genitoplasty [editorial].  J Urol. 1999;  1592-1593
    Google Scholar
  • 68 Gearhart JP. [editorial comment].  BJU Int. 2000;  86 258-259
    Google Scholar
  • 69 American Academy of Pediatrics, Committee on Genetics . Evaluation of the newborn with developmental anomalies of the external genitalia.  Pediatrics. 2000;  106 138-142
    Google Scholar
  • 70 Miller Wl, Oberfield SE, Speiser PW. et al . Regarding the consensus statement on 21-hydroxilase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology [letter].  J Clin Endocrinol Metab. 2003;  88 3456
    Google Scholar
  • 71 Nihoul-Fèkété C. Surgical management of the intersex patient: an overview in 2003 [lecture].  J Pediatr Surg. 2004;  39 144-145
    Google Scholar
  • 72 Alizai NK, Thomas DFM, Lilford RJ. et al . Feminizing genitoplasty for congenital adrenal hyperplasia: what happens at puberty?.  J Urol. 1999;  161 1588-1591
    Google Scholar
  • 73 Krege S, Walz KH, Hauffa BP. et al . Long-term follow-up of female patients with congenital adrenal hyperplasia from 21-hydroxilase deficiency, with special emphasis on the results of vaginoplasty.  BJU Int. 2000;  86 253-259
    Google Scholar
  • 74 Gastaud F, Bouvattier C, Duranteau L. et al . Impaired sexual and reproductive outcomes in women with classical forms of congenital adrenal hyperplasia.  J Clin Endocrinol Metab. 2007;  92 1391-1396
    Google Scholar
  • 75 Göllü G, Yildiz RV, Bingol-Kologlu M. et al . Ambiguous genitalia: an overview of 17 years’ experience.  J Pediatr Surg. 2007;  42 840-844
    Google Scholar
  • 76 Glassberg KI. Gender assignment and the pediatric urologist [editorial].  J Urol. 161 1308-1310
    Google Scholar
  • 77 Eroglu E, Tekant G, Gündogdu G. et al . Feminizing surgical management of intersex patients.  Pediatr Sug Int. 2004;  20 543-547
    Google Scholar
  • 78 Rangecroft L. Surgical management of ambiguous genitalia.  Arch Dis Child. 2003;  88 799-801
    Google Scholar
  • 79 Creighton SM, Liao LM. Changing attitudes to sex assignment in intersex.  BJU Int. 2004;  93 659-664
    Google Scholar
  • 80 Nabhan ZM, Rink RC, Eugster EA. Urinary tract infections in children with congenital adrenal hyperplasia.  J Pediatr Endocrinol Metab. 2006;  19 815-820
    Google Scholar
  • 81 Kryger JV, González. Urinary continence is well preserved after total urogenital mobilzation.  J Urol. 2004;  172 2384-2386
    Google Scholar
  • 82 Miranda ML, Oliveira Filho AG, Lemos-Marini SHV. et al . Labioscrotal island flap in feminizing genitoplasty.  J Pediatr Surg. 2004;  39 1030-1033
    Google Scholar
  • 83 Davies MC, Crouch NS, Woodhouse CRJ. et al . Congenital adrenal hyperplasia and lower tract symptoms.  BJU Int. 2005;  95 1263-1266
    Google Scholar
  • 84 Celayir S, Ilçe Z, Danismend N. Effects of male sex hormones on urodynamics in childhood: intersex patients are a natural model.  Pediatr Surg Int. 2000;  16 502-504
    Google Scholar
  • 85 Money J, Hampson JG, Hampson JL. Hermaphroditism: recommendations concerning assignment of sex, change of sex, and psychologic management.  Bull Johns Hopkins Hosp. 1955;  97 284-300
    Google Scholar
  • 86 Zucker KJ. Intersexuality and gender differentiation.  J Pediatr Adolec Gynecol. 2002;  15 3-13
    Google Scholar
  • 87 Reiner WG. Sex assignment in the neonate with intersex or inadequate genitalia.  Arch Pediatr Adolesc Med. 1997;  151 1044-1045
    Google Scholar
  • 88 Woodhouse CRJ. Intersex surgery in the adult.  BJU Int. 2004;  93 ((Suppl 3)) 57-65
    Google Scholar
  • 89 Creighton SM, Ransley P, Duffy P. et al . Regarding the consensus statement on 21-hydroxilase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology [letter].  J Clin Endocrinol Metab. 2003;  88 3455
    Google Scholar
  • 90 Creighton SM. Long-term outcome of feminization surgery: the London experience.  BJU Int. 2004;  93 ((Suppl 3)) 44-46
    Google Scholar
  • 91 Stikkelbroeck NMML, Beerendonk CCM, Willemsen WNP. et al . The long term outcome of feminizing genital surgery for congenital adrenal hyperplasia: anatomical, functional and cosmetic outcomes, psychosexual development, and satisfaction in adult female patients.  J Pediatr Adolesc Gynecol. 2003;  16 289-296
    Google Scholar
  • 92 Gupta DK, Shilpa S, Amini AC. et al . Congenital adrenal hyperplasia: long-term evaluation of feminizing genitoplasty and psychosocial aspects.  Pediatr Surg Int. 2006;  22 905-909
    Google Scholar
  • 93 Zucker KJ, Bradley SJ, Oliver G. et al . Psychosexual development of women with congenital adrenal hyperplasia.  Horm Behav. 1996;  30 300-318
    Google Scholar
  • 94 Meyer-Bahlburg HFL, Gruen RS, New MI. et al . Gender change from female to male in classical congenital adrenal hyperplasia.  Horm Behav. 1996;  30 319-332
    Google Scholar
  • 95 Berenbaum SA, Bailey M. Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia.  J Clin Endocrinol Metab. 2003;  88 1102-1106
    Google Scholar
  • 96 Berenbaum AS, Bryk KK, Duck SC. Psychological adjustment in children and adults with congenital adrenal hyperplasia.  J Pediatr. 2004;  144 741-746
    Google Scholar
  • 97 Consortium on the management of disorders of sex development. Clinical guidelines for the management of disorders of sex development in childhood. Rohnert Park: Intersex Society of North America [cited 15 Dec 2007]. Available from: http://www.dsdguidelines.org/htdocs/clinical/index.html 2006 ▪
    Google Scholar
  • 98 Özbey H, Darendeliler F, Kayserili H. et al . Gender assignment in female congenital adrenal hyperplasia: a difficult experience.  BJU Int. 2004;  94 388-391
    Google Scholar
  • 99 Meyer-Bahlburg HFL. Gender and sexuality in classical congenital adrenal hyperplasia.  Endocrinol Metab Clin North Am. 2001;  30 155-171
    Google Scholar
  • 100 Wisniewski AB, Migeon CJ, Malouf MA. et al . Psychosexual outcome in women affected by congenital adrenal hyperplasia due to 21-hydroxilase deficiency.  J Urol. 2004;  171 2497-2501
    Google Scholar
  • 101 Daaboul J, Frader J. Ethics and the management of the patient with intersex: a middle way.  J Pediatr Endocrinol Metab. 2001;  14 1575-1583
    Google Scholar
  • 102 Lee PA, Witchel SF. Genital surgery among females with congenital adrenal hyperplasia: changes over the past five decades.  J Pediatr Endocrinol Metab. 2002;  15 1473-1477
    Google Scholar
  • 103 Maharaj NR, Dhai A, Wiersma R. et al . Intersex conditions in children and adolescents: surgical, ethical, and legal considerations.  J Pediatr Adolesc Gynecol. 2005;  18 399-402
    Google Scholar
  • 104 Dayner JE, Lee PA, Houk CP. Medical treatment of intersex: parenteral perspectives.  J Urol. 2004;  172 1762-1765
    Google Scholar
  • 105 Graziano K, Teitelbaum DH, Hirschl RB. et al . Vaginal reconstruction for ambiguous genitalia and congenital absence of the vagina: a 27-year experience.  J Pediatr Surg. 2002;  37 955-960
    Google Scholar
  • 106 Consensus statement on the management of intersex disorders by the Lawson Wilkins Pediatric Society and the European Society for Paediatric Endocrinology.  Pediatrics. 2006;  118 488-500
    Google Scholar

Correspondence

Dr. Joao L. Pippi Salle

The Hospital for Sick Children

Urology

Toronto

Canada

Phone: 416/813 64 60

Fax: 416/813 64 61

Email: pippi.salle@sickkids.ca