Wisniewski, A.B. et al. Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. J. Clin. Endocrinol. Metab. 85, 2664−2669

Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, United States
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 09/2000; 85(8):2664-9. DOI: 10.1210/jc.85.8.2664
Source: PubMed


Controversy concerning the most appropriate treatment guidelines for intersex children currently exists. This is due to a lack of long-term information regarding medical, surgical, and psychosexual outcome in affected adults. We have assessed by questionnaire and medical examination the physical and psychosexual status of 14 women with documented complete androgen insensitivity syndrome (CAIS). We have also determined participant knowledge of CAIS as well as opinion of medical and surgical treatment. As a whole, secondary sexual development of these women was satisfactory, as judged by both participants and physicians. In general, most women were satisfied with their psychosexual development and sexual function. Factors reported to contribute to dissatisfaction were sexual abuse in one case and marked obesity in another. All of the women who participated were satisfied with having been raised as females, and none desired a gender reassignment. Although not perfect, the medical, surgical, and psychosexual outcomes for women with CAIS were satisfactory; however, specific ways for improving long-term treatment of this population were identified.

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    • "This leads, despite normal to high male testosterone levels produced by their abdominal testes, to a female phenotype (Oakes et al. 2008). Studies using quantitative measures of psychosexual development indicate that individuals with CAIS are nearly always androphilic (sexually attracted to men), have a female gender identity, and show female-typical gender role behavior (Masica et al. 1971; Wisniewski et al. 2000; Hines et al. 2003). Spatial abilities in this group have only been studied by means of the Wechsler Intelligence Scale for Adults (WAIS) and for Children (WISC). "
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    ABSTRACT: 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    No preview · Article · Dec 2014 · Cerebral Cortex
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    • "They are thus born with female external genitalia, develop a female phenotype, are reared as girls, and undergo a feminizing puberty as a result of the aromatization of their testosterone to estradiol (Cheikhelard et al., 2009). Behavior in women with CAIS appears to be female-typical (Hines et al., 2003; Wisniewski et al., 2000), as do their spontaneous otoacoustic emissions, a sexually differentiated aspect of the auditory system thought to reflect sex differences in brain stem organization (Wisniewski et al., 2014). There have been, however, no studies of brain structure or patterns of neural activation in women with CAIS. "
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    ABSTRACT: Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images, We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls.
    Full-text · Article · Oct 2014 · Hormones and Behavior
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    • "Yet, recent evidence indicates that in anthropoid primates, male sexual brain differentiation is brought about by direct actions of androgens on androgen receptors (Wallen, 2005). Observations in women with complete androgen insensitivity syndrome, who exhibit femaletype gender-related psychological characteristics in spite of testosterone levels in the male range (Wisniewski et al., 2000; Hines et al., 2003), also support the idea that male brain differentiation in primates is not achieved by estrogen derived from testosterone. In contrast to this discrepancy in male brain development, female sexual behavior appears to be estrogendependent in both, rodents and primates (Zehr et al., 1998; Wallen and Zehr, 2004). "
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    ABSTRACT: The developing nervous system is a potential target of environmental contaminants such as polybrominated diphenylethers (PBDE), which accumulate in the biosphere. We compared effects of 2,2',4,4',5-pentabromo-BDE (PBDE99), a PBDE congener present in environmental samples, and PCB on brain development. Time-pregnant rats were subcutaneously injected with PBDE99 (1 or 10 mg/kg), the PCB mixture Aroclor 1254 (10 mg/kg), or vehicle from gestational day 10 to 18. mRNA levels of genes involved in central control of reproductive functions and sexual behavior were analyzed by real time RT PCR in two sexually dimorphic brain regions, medial preoptic area (MPO) and ventromedial hypothalamus (VMH) of adult offspring of both sexes. Exposure to PBDE99 or the PCB mixture during pre- and postnatal development affected mRNA expression levels in a treatment-, region- and sex-specific manner, and changed the sensitivity of target genes to estradiol. The sex difference in progesterone receptor mRNA levels of VMH normally seen in untreated controls was abolished by both, PBDE99 and PCB. Estrous cycles were significantly affected, and preliminary experiments suggest an impairment of female sexual behavior. Our data indicate that developmental exposure to PBDE99 at doses below signs of general toxicity affects the regulation of estrogen target genes in rat brain. Since PBDE99 was detected in blood and adipose tissue of adult offspring, these effects may result from interactions with developmental processes, with adult functions, or a combination of both.
    Full-text · Article · Apr 2013 · General and Comparative Endocrinology
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