scholarly journals No Evidence for a Difference in 2D:4D Ratio between Youth with Elevated Prenatal Androgen Exposure due to Congenital Adrenal Hyperplasia and Controls

2020 ◽  
Author(s):  
Gideon Nave ◽  
Christina M. Koppin ◽  
Dylan Manfredi ◽  
Gareth Richards ◽  
Steven J. Watson ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Large Body ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Left Hand ◽  
Androgen Exposure ◽  
Wide Range ◽  
Prenatal Androgen Exposure ◽  
21 Hydroxylase Deficiency ◽  
Prenatal Androgen

AbstractThe second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: □ = -0.001 (−0.008, 0.006)]; females: □ = -0.004 [-0.015, 0.007]; males: □ = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

Congenital adrenal hyperplasia: molecular mechanisms resulting in 21-hydroxylase deficiency

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S315-S320 ◽  
Author(s):  
Patricia A. Donohoue ◽  
Cornelis Van Dop ◽  
Nicholas Jospe ◽  
Claude J. Migeon
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Molecular Mechanisms ◽  
Sequence Data ◽  
Phenotypic Expression ◽  
Restriction Pattern ◽  
Class Iii ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Wide Range ◽  
21 Hydroxylase Deficiency

Abstract 21-Hydroxylase deficiency resulting in congenital adrenal hyperplasia (CAH) is a HLA-linked autosomal recessive disorder that has a wide range of phenotypic expression. Two homologous 21-hydroxylase genes (21-OHA and 21-OHB) occur within the Class III region of the major histocompatibility complex, but only one (21-OHB) appears to function in adrenal steroidogenesis. Our restriction maps, and initial sequence data from White et al. (Pediatr Res 20:274A (1986)) for the two human 21-OH genes reveal a high degree of homology between these genes and a reading frame shift mutation in the 21-OHA gene respectively. Among fourteen control subjects, the intragenic restriction patterns of the 21-OHA and 21-OHB genes are invariant. The few restriction fragment length polymorphisms (RFLPs) found in some controls result from polymorphic restriction sites outside the 21-OH genes. In patients with CAH, several different mechanisms for mutation of the 21-OHB gene have been described: 1) deletion of the unique sequences of the 21-OHB gene, 2) conversion of the unique sequences of the 21-OHB gene to those of 21-OHA, and 3) mutations of 21-OHB which do not result in a detectable alteration of restriction pattern (e.g., point mutations). Duplication of the 21-OHA gene has been found in some patients with attenuated CAH; however, the significance of this finding remains unclear.

scholarly journals Personality and congenital adrenal hyperplasia: Possible effects of prenatal androgen exposure

2009 ◽  
Vol 55 (2) ◽  
pp. 285-291 ◽  
Author(s):  
Greta A. Mathews ◽  
Briony A. Fane ◽  
Gerard S. Conway ◽  
Charles G.D. Brook ◽  
Melissa Hines
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Androgen Exposure ◽  
Prenatal Androgen Exposure ◽  
Prenatal Androgen

Executive functioning in children with congenital adrenal hyperplasia

2016 ◽  
Vol 65 (1) ◽  
pp. 49-52 ◽  
Author(s):  
A Monica Agoston ◽  
Maria Teresa Gonzalez-Bolanos ◽  
Margaret Semrud-Clikeman ◽  
Nancy Vanderburg ◽  
Kyriakie Sarafoglou
Keyword(s):  
Sex Differences ◽  
Executive Functioning ◽  
Congenital Adrenal Hyperplasia ◽  
Bone Age ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Estrogen Exposure ◽  
Androgen Exposure ◽  
21 Hydroxylase Deficiency ◽  
The Impact

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder characterized by impaired cortisol synthesis leading to excessive production of adrenal androgens. Prenatal and postnatal exposure to excess androgens may increase neural vulnerability to insult and affect cognitive functions, particularly dopamine-dependent neural circuits responsible for executive functioning (EF). Our study aimed to investigate relationship between more pronounced androgen exposure and EF-related behaviors in children with CAH, as well as sex differences in these associations. Parents of patients with CAH (n=41, boys=17, girls=24; age: M=8.41, SD=4.43) completed the Behavior Rating Inventory of Executive Function (BRIEF), a measure assessing behavioral manifestations of EF. Assessments of bone age advancement, a proxy of cumulative androgen exposure, were analyzed. Advanced bone age predicted more inhibition difficulties in boys but not in girls, and more difficulties in all other BRIEF domains in the total sample. Excessive androgen production affected EF such that more advanced bone age led to more EF-related difficulties. Sex differences in inhibition may result from estrogen exposure moderating the impact of androgens in girls but not in boys. Future interventions may include targeting EF in patients with CAH to enhance quality of life and reduce cognitive consequences associated with this disease.

scholarly journals Effects of Pre and Post-Natal Androgen Exposure on Psychosexual Aspects and Gender Change in Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A500-A501
Author(s):  
Rafael Loch Batista ◽  
Marlene Inacio ◽  
Mirela Costa de Miranda ◽  
Guiomar Madureira ◽  
Larissa Garcia Gomes ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Male Gender ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Androgen Exposure ◽  
Sex Assignment ◽  
And Gender ◽  
21 Hydroxylase Deficiency ◽  
Gender Change

Abstract Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up 90% of CAH. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess in both salt-wasting (SW) or simple virilizing (SV) forms. As androgens play a role in the human psychosexual development favoring male psychosexuality, this study was designed to evaluate the impact of androgen exposure on the psychosexuality of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort includes 46,XX individuals (115 female-assigned; 8 male-assigned) with a molecular diagnosis of CAH due to CYP21A2 pathogenic variants in homozygous or compounds heterozygous state. External genitalia virilization was scored using Prader scale. Phenotype, time at diagnosis, sex assignment, and gender change were assessed. The gender role at childhood was assessed through the playmates and toys profile at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report sexual identity. Compliance of glucocorticoid replacement was assessed by adequate testosterone and androstenedione serum levels for age. Results: CAH was diagnosed at the neonatal time in 73% (n=78). Fifth-nine (51%) had the SW form and 49% (n=56) had the SV form. While all cases of SW were diagnosed at the neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (p=<.001). The median of Prader score was 3 in both forms. Male sex assignment was associated with more virilized external genitalia (p=.002). Gender change occurred in 6 cases (female to male), all with SV form. The prader score was higher among those who changed gender (p=.01). All of those who changed their gender had poor treatment compliance. A total of 13% (n=15) of all groups defined themselves as homosexual. There was a strong association between male toys and preference for male playmates in childhood with homosexuality and male gender identity in adulthood with both gender change from female to male and homosexuality. Conclusion: Prenatal androgen exposure favors male psychosexuality in 46,XX CAH individuals as observed by the association between highest Prader scores and all assessed psychosexual outcomes. This influence is also substantiated by post-natal androgen exposure as observed by compliance issues and late diagnosis among those who changed from female to male gender.

scholarly journals Congenital adrenal hyperplasia – current insights in pathophysiology, diagnostics and management

2021 ◽  
Author(s):  
Hedi L Claahsen – van der Grinten ◽  
Phyllis W Speiser ◽  
S Faisal Ahmed ◽  
Wiebke Arlt ◽  
Richard J Auchus ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Large Body ◽  
Well Being ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
New Developments ◽  
Autosomal Recessive Disorders ◽  
Alternative Medications ◽  
21 Hydroxylase Deficiency ◽  
Recessive Disorders

Abstract Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21- hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000 there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in congenital adrenal hyperplasia with special attention to these new developments.

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