Skip to main content Accessibility help
×
Home
  • Print publication year: 2004
  • Online publication date: May 2010

22 - The XY female

from Part III - Management of specific disorders

Summary

Introduction

In most pregnancies, fetal sexual development progresses smoothly down one of two paths leading to a male infant with an XY karyotype, scrotal testes and standard male genitalia or a female infant with an XX karyotype, ovaries and a uterus, and standard female external genitalia. However human fetal sexual determination and differentiation is complex and can be diverted from these dual standard pathways at a multitude of different points. When such a diversion occurs, the developing fetus can either switch over to the other pathway or blend the two, resulting in the birth of an intersex child.

Named androgynes by the Greeks, and later hermaphrodites by the Romans, no clear definition exists for the term “intersex”, and correspondingly incidence figures vary greatly according to the conditions included (Blackless et al., 2000; Duckett et al., 1993; Quigley et al., 1995). In this chapter, the term intersex is used to mean a person with a mix or blend of the physically defining features (i.e. karyotype, gonadal structure, internal genitalia and external genitalia) usually associated with standard males and females. The term intersex, therefore, covers a diverse range of conditions encompassing individuals with standard male or female genitalia, who may have a variety of internal genital organs and karyotypes, and also those with ambiguous external genitalia. There are currently over 15 recognized intersex conditions, and in many of these there is an XY karyotype or some cells that are XY (Table 22.1).

REFERENCES
Adachi, M, Takayanagi, R, Tomura, A et al. (2000). Androgen-insensitivity syndrome as a possible coactivator disease. N Engl J Med 343, 856–862
Adamski, J, Jakob, F J (2001). A guide to 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 171, 1–4
Ahmed, S F, Cheng, A, Dovey, L et al. (2000). Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab 85, 658–665
Arnhold, I J P, Latronico, A C, Batista, M C, Mendonca, B B (1999). Menstrual disorders and infertility caused by inactivating mutations of the luteinising hormone receptor gene. Fertil Steril 71, 597–601
Bangsboll, S, Qvist, I, Lebech, P E, Lewinsky, M (1992). Testicular feminization syndrome and associated gonadal tumours in Denmark. Acta Obstet Gynecol Scand 71, 63–66
Barbaux, S, Niaudet, P, Gubler, M C et al. (1997). Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 17(4), 467–470
Batch, J A, Patterson, M N, Hughes, I A (1992). Androgen insensitivity syndrome. Reprod Med Rev 1, 131–150
Berkovitz, G D, Seeherunvong, T (1998). Abnormalities of gonadal differentiation. Baillières Clin Endocrinol Metab 12, 133–142
Berta, P, Hawkins, J R, Sinclair, A H et al. (1990). Genetic evidence equating SRY and the testis-determining factor. Nature 348, 448–450
Blackless, M, Charuvastra, A, Derryck, A, Fausto-Sterling, A, Lauzanne, K, Lee, E (2000). How sexually dimorphic are we? Review and synthesis. Am J Hum Biol 12, 151–166
Boehmer, A L, Brinkmann, A O, Sandkuijl, L A et al. (1999). 17 Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations. J Clin Endocrinol Metab 84, 4713–4721
Boehmer, A L, Bruggenwirth, H, Assendelft, C et al. (2001). Genotype versus phenotype in families with androgen insensitivity syndrome. J Clin Endocrinol Metab 86, 4151–4160
Bose, H S, Sugawara, T, Strauss, J F, III, Miller, W L (1996). The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. International Congenital Lipoid Adrenal Hyperplasia Consortium. N Engl J Med 335, 1870–1878
Bradley, S J, Oliver, G D, Chernick, A B, Zucker, K J (1998). Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months, and a psychosexual follow-up in young adulthood. Pediatrics 102, E9
Calikoglu, A S (1999). Should boys with micropenis be reared as girls?J Pediatr 134, 537–538
Canto, P, Vilchis, F, Chavez, B et al. (1997). Mutations of the 5 alpha-reductase type 2 gene in eight Mexican patients from six different pedigrees with 5 alpha-reductase-2 deficiency. Clin Endocrinol 46, 155–160
Canto, P, Chesnaye, E, Lopez, M et al. (2000). A mutation in the 5′ non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism. J Clin Endocrinol Metab 85, 1908–1911
Cassio, A, Cacciari, E, D'Errico, A et al. (1990). Incidence of intratubular germ cell neoplasia in androgen insensitivity syndrome. Acta Endocrinol 123, 416–422
Chang, H J, Clark, R D, Bachman, H (1990). The phenotype of 45,X/46,XY mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet 46, 156–167
Chase, C (1998). Surgical progress is not the answer to intersexuality. J Clin Ethics 9, 385–392
Costa, E M, Mendonca, B B, Inacia, M, Arnhold, I J, Silva, F A, Lodovici, O (1997). Management of ambiguous genitalia in pseudohermaphrodites: new perspectives on vaginal dilation. Fertil Steril 67, 229–232
Creighton, S M, Minto, C L (2001). Managing intersex. Br Med J 323, 1264–1265
Creighton, S M, Minto, C L, Steele, S J (2001). Objective cosmetic and anatomical outcomes at adolescence of feminising surgery for ambiguous genitalia done in childhood. Lancet 358, 124–125
Dewhurst, C J, Ferreira, H P, Gillett, P G (1971). Gonadal malignancy in XY females. J Obstet Gynaecol Br Commonwealth 78, 1077–1083
Diamond, M, Sigmundson, H K (1997). Sex reassignment at birth. Long-term review and clinical implications. Arch Pediatr Adolesc Med 151, 298–304
Diamond, M, Binstock, T, Kohl, J V (1996). From fertilization to adult sexual behavior. Horm Behav 30, 333–353
Donahoe, P K (1987). The diagnosis and treatment of infants with intersex abnormalities. Pediatr Clin North Am 34, 1333–1348
Dreger, A D (1998). ‘Ambiguous sex’ — or ambivalent medicine? Ethical issues in the treatment of intersexuality. Hastings Cent Rep 28, 24–35
Duckett, J W, Baskin, L S (1993). Genitoplasty for intersex anomalies. Eur J Pediatr 152(Suppl. 2), S80–S84
Edmonds D K (1989). Intersexuality. In Dewhurst's Practical Paediatric and Adolescent Gynaecology, Edmonds D K, ed., pp. 6–26. Butterworths, London
Ellis, A (1945). The sexual psychology of human hermaphrodites. Psychosom Med 7, 108–125
Faisal, A S, Iqbal, A, Hughes, I A (2000). The testosterone: androstenedione ratio in male undermasculinization. Clin Endocrinol 53, 697–702
Geller, D H, Auchus, R J, Mendonca, B B, Miller, W L (1997). The genetic and functional basis of isolated 17,20-lyase deficiency. Nat Genet 17, 201–205
Griffin, J E (1992). Androgen resistance: the clinical and molecular spectrum. N Engl J Med 326, 611–618
Hampson, J G (1955). Hermaphroditic genital appearance, rearing and eroticism in hyperadrenocorticism. Bull Johns Hopkins Hosp 96, 265–273
Herdt, G H, Davidson, J (1988). The Sambia ‘Turnim-Man’: sociocultural and clinical aspects of gender formation in male pseudohermaphrodites with 5-alpha-reductase deficiency in Papua New Guinea. Arch Sex Behav 17, 33–56
Hurt, W G, Bodurtha, J N, McCall, J B, Ali, M M (1989). Seminoma in pubertal patient with androgen insensitivity syndrome. Am J Obstet Gynecol 161, 530–531
Imperato-McGinley, J (1979). Androgens and the evolution of male gender identity among male PSH with 5 alpha reductase deficiency. N Engl J Med 300, 1233–1237
Imperato-McGinley, J (1994). 5-Alpha-reductase deficiency: human and animal models. Eur Urol 25(Suppl. 1), 20–23
Imperato-McGinley, J, Guerrero, L, Gautier, T, Petterson, R E (1974). Steroid 5-alpha-reductase deficiency in man. An inherited form of male pseudohermaphroditism. Science 186, 1213–1215
Ingram, J M (1981). The bicycle seat stool in the treatment of vaginal agenesis and stenosis: a preliminary report. Am J Obstet Gynecol 140, 867–873
Jadresic, L, Leake, J, Gordon, I et al. (1990). Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome). J Pediatr 117, 717–725
Josso, N, Briard, M L (1980). Embryonic testicular regression syndrome: variable phenotypic expression in siblings. J Pediatr 97, 200–204
Katz, M D, Kligman, I, Cai, L Q et al. (1997). Paternity by intrauterine insemination with sperm from a man with 5alpha-reductase-2 deficiency. N Engl J Med 336, 994–997
Keller, R (1940). Historical and cultural aspects of hermaphroditism. Ciba Symp 2, 466–470
Krob, G, Braun, A, Kuhnle, U (1994). True hermaphroditism: geographical distribution, clinical findings, chromosomes and gonadal histology. Eur J Pediatr 153, 2–10
Kwok, C, Tyler-Smith, C, Mendonca, B B et al. (1996). Mutation analysis of the 2 kb 5′ to SRY in XY females and XY intersex subjects. J Med Genet 33, 465–468
Ludwig, G (1999). Micropenis and apparent micropenis — a diagnostic and therapeutic challenge. Andrologia 31, 27–30
MacDonald, P C, Madden, J D, Brenner, P F, Wilson, J D, Siiteri, P K (1979). Origin of estrogen in normal men and in women with testicular feminization. J Clin Endocrinol Metab 49, 905–916
Manuel, M, Katayama, P K, Jones, H W Jr (1976). The age of occurrence of gonadal tumours in intersex patients with a Y chromosome. Am J Obstet Gynecol 124, 293–300
Marcantonio, S M, Fechner, P Y, Migeon, C J, Perlman, E J, Berkovitz, G D (1994). Embryonic testicular regression sequence: a part of the clinical spectrum of 46,XY gonadal dysgenesis. Am J Med Genet 49, 1–5
Marcus, R, Leary, D, Schneider, D L, Shane, E, Favus, M, Quigley, C A (2000). The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome. J Clin Endocrinol Metab 85, 1032–1037
McElreavey, K, Fellous, M (1999). Sex determination and the Y chromosome. Am J Med Genet 89, 176–185
Mendonca, B B, Barbosa, A S, Arnhold, I J, McElreavey, K, Fellous, M, Moreira-Filho C A (1994). Gonadal agenesis in XX and XY sisters: evidence for the involvement of an autosomal gene. Am J Med Genet 52, 39–43
Minto, C L, Liao, L M, Conway, G S, Creighton, S M (2003a). Sexual function in adult women with complete androgen insensitivity syndrome. Fertil Steril 80, 157–164
Minto, C L, Liao, L M, Woodhouse, C R, Ransley, P G, Creighton, S M (2003b). The effect of clitoral surgery on sexual outcome in individuals who have intersex conditions with ambiguous genitalia: a cross-sectional study. Lancet 361, 1252–1257
Money, J (1985). Pediatric sexology and hermaphroditism. J Sex Marital Ther 11, 139–156
Money, J, Hampson, J G, Hampson, J L (1955). An examination of some basic sexual concepts: the evidence of human hermaphroditism. Bull Johns Hopkins Hosp 97, 301–319
Money, J, Devore, H, Norman, B F (1986). Gender identity and gender transposition: longitudinal outcome study of 32 male hermaphrodites assigned as girls. J Sex Marital Ther 12, 165–181
Morris, J M (1953). The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol 65, 1192–1211
Oesch, I L, Pinter, A, Ransley, P G (1987). Penile agenesis: a report of six cases. J Pediatr Surg 22, 172–174
Pang, S (2001). Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency. Endocrinol Metab Clin North Am 30, 81–99
Quigley, C A, Bellis, A, Marschke, K B, el Awady, M K, Wilson, E M, French, F S (1995). Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 16, 271–321
Quint, E H, Strickland, J L (2001). Management quandary. Testicular feminization. J Pediatr Adolesc Gynecol 14, 99–100
Randall, V A (1994). Role of 5 alpha-reductase in health and disease. Baillières Clin Endocrinol Metab 8, 405–431
Reilly, J M, Woodhouse, C R (1989). Small penis and the male sexual role. J Urol 142, 569–571
Rey, R, Picard, J-Y (1998). Embryology and endocrinology of genital development. Clin Endocrinol Metab 12, 17–33
Rosenfield, R L, Lucky, A W, Allen, T D (1980). The diagnosis and management of intersex. Curr Probl Pediatr 10, 1–66
Rosler, A, Silverstein, S, Abeliovich, D (1996). A (R80Q) mutation in 17 beta-hydroxysteroid dehydrogenase type 3 gene among Arabs of Israel is associated with pseudohermaphroditism in males and normal asymptomatic females. J Clin Endocrinol Metab 81, 1827–1831
Rumsby G (1997). Molecular biology of steroid biosynthesis. In Molecular Endocrinology. Genetic Analysis of Hormones and their Receptors, Rumsby G, Farrow S M, eds., pp. 179–202. BIOS Scientific, Oxford, UK
Russell, M H, Wachtel, S S, Davis, B W et al. (1982). Ovarian development in 46,XY gonadal dysgenesis. Hum Genet 60, 196–199
Rutgers, J L, Scully, R E (1991). The androgen insensitivity syndrome (testicular feminisation): a clinicopathological study of 43 cases. Int J Gynecol Pathol 10, 126–144
Schafer, A J, Dominguez-Steglich, M A, Guioli, S et al. (1995). The role of SOX9 in autosomal sex reversal and campomelic dysplasia. Philos Trans Roy Soc Lond B Biol Sci 350, 271–277
Schober, J M (1998). Early feminizing genitoplasty or watchful waiting. J Pediatr Adolesc Gynecol 11, 154–156
Sinnecker, G H, Hiort, O, Nitsche, E M for the German Collaborative Intersex Study Group (1997). Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. Eur J Pediatr 156, 7–14
Slaney, S F, Chalmers, I J, Affara, N A, Chitty, L S (1998). An autosomal or X linked mutation results in true hermaphrodites and 46,XX males in the same family. J Med Genet 35, 17–22
Slijper, F M, Frets, P G, Boehmer, A L, Drop, S L, Niermeijer, M F (2000). Androgen insensitivity syndrome (AIS): emotional reactions of parents and adult patients to the clinical diagnosis of AIS and its confirmation by androgen receptor gene mutation analysis. Horm Res 53, 9–15
Soule, S G, Conway, G, Prelevic, G M, Prentice, M, Ginsburg, J, Jacobs, H S (1995). Osteopenia as a feature of the androgen insensitivity syndrome. Clin Endocrinol 43, 671–675
Stavrou, S S, Zhu, Y S, Cai, L Q et al. (1998). A novel mutation of the human luteinizing hormone receptor in 46,XY and 46,XX sisters. J Clin Endocrinol Metab 83, 2091–2098
Swyer, G (1955). Male pseudohermaphroditism: a hitherto undescribed form. Br Med J , 709–710
Tajima, T, Fujieda, K, Kouda, N, Nakae, J, Miller, W L (2001). Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency. J Clin Endocrinol Metab 86, 3820–3825
Verp, M S, Simpson, J L (1987). Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet 25, 191–218
Verp, M S, Harrison, H H, Ober, C et al. (1992). Chimerism as the etiology of a 46,XX/46,XY fertile true hermaphrodite. Fertil Steril 57, 346–349
Walker, A M, Walker, J L, Adams, S, Shi, E, McGlynn, M, Verge, C F (2000). True hermaphroditism. J Paediatr Child Health 36, 69–73
Weber, A M, Walters, M D, Schover, L R, Mitchinson, A (1995). Vaginal anatomy and sexual function. Obstet Gynecol 86, 946–949
Wiersma, R (2001). Management of the African child with true hermaphroditism. J Pediatr Surg 36, 397–399
Yanase, T.17 Alpha-hydroxylase/17,20-lyase defects (1995). J Steroid Biochem Mol Biol 53, 153–157
Zenteno, J C, Canto, P, Kofman-Alfaro, S, Mendez, J P (1999). Evidence for genetic heterogeneity in male pseudohermaphroditism due to Leydig cell hypoplasia. J Clin Endocrinol Metab 84, 3803–3806
Zhu, Y S, Katz, M D, Imperato-McGinley, J (1998). Natural potent androgens: lessons from human genetic models. Baillières Clin Endocrinol Metab 12, 83–113
Zucker, K J (1999). Intersexuality and gender identity differentiation. Annu Rev Sex Res 10, 1–69