Jennifer J. Bell

Gender Change from Female to Male in Classical Congenital Adrenal Hyperplasia

The psychoendocrinology of the development of normal gender identity and its variations is poorly understood. Studies of gender development in individuals born with endocrinologically well-characterized intersex conditions are heuristically valuable for the disaggregation of factors that are acting in concert during normal development. Four 46,XX individuals with classical congenital adrenal hyperplasia (CAH) and atypical gender identity entered a comprehensive research protocol including systematic interviews and self-report inventories on gender role behavior and identity, sexual history, and psychiatric history. Some of the data on gender variables were compared to data from 12 CAH women with the salt-wasting variant (CAH-SW) with female gender identity. The four patients (ages 28, 35, 38, and 30 years) represented three different subtypes of classical early-onset CAH: 21-OH deficiency, simple virilizing (CAH-SV); 21-OH deficiency, salt-wasting (CAH-SW); and 11-beta-OH deficiency. Their medical histories were characterized by delay beyond infancy or lack of surgical feminization of the external genitalia and progressive virilization with inconsistent or absent glucocorticoid replacement therapy. Although three patients had undergone one or more genital surgeries, all had retained at least some orgasmic capacity. In regard to childhood gender-role behavior, the four gender-change patients tended to be more masculine or less feminine than (behaviorally masculinized) CAH-SW controls. All patients were sexually attracted to females only. The process of gender change was gradual and extended well into adulthood. The most plausible factors contributing to cross-gender identity development in these patients appeared to be neither a particular genotype or endocrinotype nor a sex-typing bias on the part of the parents but a combination of a gender-atypical behavioral self-image, a gender-atypical body image, and the development of erotic attraction to women. Implications for psychosocial management are also discussed.

Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels

Background:Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.Methods:Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.Results:Twenty-four million (18% of 134 million live births ≥32 wk gestational age from 184 countries; uncertainty range: 23–26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800–477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000–131,000), with a 24% risk for death (114,100; uncertainty range: 59,700–172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.Conclusion:Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

Studies of Human Chorionic Gonadotropin

Publisher Summary This chapter focuses on human chorionic gonadotropin (HCG), a glycoprotein hormone produced by the placenta that appears in significant quantities in the urine during the first trimester of pregnancy. The mean level of urinary HCG produced during the first trimester is 30,000–50,000 IU in 24 hours, equivalent to a maximum of approximately 3 mg of hormone. The high proline content is of particular interest because proline is an uncommon amino acid in most proteins and only collagen appears to have a higher content than HCG. Equilibrium sedimentation studies of reduced, alkylated HCG in the ultracentrifuge indicated that the molecular weight value had fallen to approximately one-half of that of the native hormone. Interchange of the HCG subunits with other molecules might lead to the appearance of different substances possessing other biological activities. Another possibility is that the pooled urinary material from which the HCG was purified was contaminated with a significant quantity of postmenopausal urine.

Psychopathology and social functioning in women with Turner syndrome.

Turner syndrome (TUS) in women is associated with sex chromosome abnormalities, ovarian dysgenesis with estrogen deficiency, and short stature. The goal of this study was to assess the long-term effects of these sex chromosome and hormonal anomalies on psychopathology and social functioning. We report interview and questionnaire data concerning lifetime history of mental disorders and current psychiatric symptoms. Also reported are data from questionnaires and interviews evaluating social functioning as measured by education, occupation, personal resources, and sexual behavior. Twenty-three TUS women were studied and compared with 23 closely matched women with constitutional short stature (CSS) and with 10 normal sisters of the TUS women. TUS women reported generally less mental disorder and comparable rates of psychiatric symptoms. On the other hand, they had lower overall functioning on a measure of global psychological health and had more impairment in social functioning as measured by achievement of adult milestones. We conclude that TUS women display less mental illness by positive symptom-oriented criteria but also less mental health when day-to-day functioning is considered. Our data suggest that differences in TUS women cannot be explained solely by short stature and may be related to other psychosocial, genetic, endocrine, or CNS effects of the syndrome.

Cognitive Ability and Everyday Functioning in Women with Turner Syndrome

This paper presents results from an assessment of cognitive ability and everyday functioning in a group of adult women with Turner syndrome (TUS). Twenty-three TUS women were compared with 23 matched controls with constitutional short stature (CSS). A subgroup of 10 TUS women were compared with their nondisabled female siblings. On the Wechsler Adult Intelligence Test-Revised (Wechsler, 1981), no significant group differences were found in Verbal IQ. There were significant group differences for Performance IQ and Full Scale IQ, largely due to specific deficits in the area of spatial and mathematical ability. These difficulties were also evident on the Benton Visual Retention Test-Revised (Benton, 1974). TUS individuals had significantly lower educational attainment than CSS controls but did not differ from their siblings. TUS individuals had significantly lower occupational attainment than the women in both comparison groups.

Idiopathic Precocious Puberty in Girls: Psychiatric Follow-up in Adolescence

Precocious puberty leads to conspicuous discrepancy between physique and chronological age associated with an array of psychosocial sequelae. Clinical case reports have suggested considerable psychopathology in some children with this condition which may continue into teenage and young adulthood. We present data from a first systematic controlled follow-up study of 16 adolescent girls with a history of idiopathic precocious puberty compared to closely pair-matched adolescent control subjects of comparable pubertal status and normal pubertal history. The results show little difference in body image, self-regard, and definite psychiatric diagnoses but slightly increased psychopathologic symptomatology, especially in the areas of conduct problems, and psychosomatic complaints usually associated with menstruation. We conclude that idiopathic precocious puberty in girls is associated with a long-term risk of minor psychopathologic symptomatology.

Effect of human growth hormone on amobarbital metabolism in children

Drug metabolism changes during the course of growth and development. Hormones mediate somatic growth and may mediate other developmental changes. To determine the effect of human growth hormone (hGH) on human drug metabolism, 6 hGH‐deficient children were given single oral doses of amobarbital before and 6 wk after beginning hGH replacement therapy. Amobarbital was selected as a marker of hepatic microsomal oxidation. Half‐lives rose from 13.89 ± 2.78 hr to 22.75 ± 3.97 hr, volume of distribution was unchanged, and clearance fell from 62.2 ± 15.2 ml/kg/hr to 31.2 ± 11.4 ml/kg/hr. Results indicate that hGH slows the metabolism of amobarbital, probably through an effect on the hepatic microsomal drug‐oxidizing system.

Gender role development in two clinical syndromes: Turner syndrome versus constitutional short stature.

Abstract Turner syndrome (TUS) in girls causes sex chromosome abnormalities, ovarian dysgenesis with estrogen deficiency, and short stature. The goal of this study was to assess the long-term effects of sex chromosome and hormonal anomalies on female gender role development. The authors report data from an interview assessing gender role development in 23 TUS women, compared with 23 closely matched women with constitutional short stature and with 10 normal sisters of the TUS women. The results show more stereotypic feminine behavior in childhood, adolescence, and adulthood in the TUS subjects. The authors conclude that the clinical features of TUS do not impede normal female gender development. Furthermore, the data suggest that the tendency to greater femininity in TUS women cannot be explained solely by short stature and may be related to other psychosocial, endocrine, or brain effects of the syndrome.

Idiopathic precocious puberty in girls: Psychosexual development

A promising model syndrome for the examination of the role of physical maturation in the development of female sexuality is idiopathic precocious puberty (IPP). In this first controlled study of psychosexual development in IPP females, 16 females between 13 and 20 years of age with a history of IPP were compared to 16 control subjects with a history of normal puberty pair-matched to the index subjects on the basis of sex, race, age, socioeconomic level, and menarcheal status. The psychosexual history and the current psychosexual status were assessed by a systematic half-structured interview. The IPP females on average passed the psychosexual milestones at an earlier age than their normal maturing peers, with a particularly early onset of masturbation. Those who were sociosexually active tended to report a higher total orgasmic outlet and a higher sex drive. There was no increase in homosexuality among IPP girls. The timing of puberty has a (modest) influence on psychosexual development in females.

Psychosexual Quality of Life in Adult Intersexuality: The Example of Congenital Adrenal Hyperplasia (CAH)

A fundamental aspect of the quality of life in adolescence and adulthood is psychosexuality. It comprises three interrelated aspects: (1) gender role behavior and gender identity; (2) sexual life, with its four components of sexual orientation, courtship, partner bonding, and genital sexuality; (3) reproduction and parenting. Intersexuality tends to affect all three aspects of psychosexuality. In this chapter, we will use data on the syndrome of classical congenital adrenal hyperplasia (CAH) in 46,XX individuals with 21-hydroxylase deficiency as an illustrative example.