Effects of Adrenal Androgens on Gender-typed Behavior in Girls With Turner Syndrome

NCT05346159 | Completed

• 1 other identifier: soh-med-22-04-09
• Study Type: observational
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

Turner syndrome (TS) is a genetic disorder in which there is loss of all or part of the second X chromosome and occurs in 1/2500 live female births. TS is characterized by short stature and endocrine abnormalities, such as the loss of ovarian function (Gonadal dysgenesis) and estrogen deficiency. The absence of pubertal development is one of the most common clinical features of patients with TS, who should have experienced a sex hormone surge if the hypothalamic-pituitary-gonadal axis was activated normally . Gonadarche and adrenarche are regarded as processes that are independent of each other. The function of adrenal gland is independent of true (central/complete/gonadotropin- dependent) puberty . Adrenal androgen in Turner syndrome shows a wide spectrum, ranging from normal to highly elevated. X-linked genes affect the brain in at least two ways: by directly acting on the brain and by indirectly acting on the gonads to induce differences in specific gonadal secretions (i.e., hormones) that have specific effects on brain development. The changes in brain and behavioral/ cognitive phenotypes in TS individuals may be the result of a direct genetic factor, an indirect hormonal factor, or a combination of the two factors . To evaluate direct effect of X chromosome, a lot of neuroimaging studies have revealed both neuroanatomical and neurofunctional changes in patients with TS. S. C. Mueller (2013) reported that oestrogen deficiency exhibits paradoxical healthy male-like patterns (i.e., a larger amygdala but reduced hippocampal volume). This finding confirms the indirect hormonal effect on the brain that are likely attributed to the effect of androgen on the brain or may be due to active role of estrogen in feminization of brain . The cognitive phenotypes of TS include severe deficits in multiple cognitive domains: visual-spatial ability, mathematical processing, and social cognition. Regarding intelligence, numerous TS studies have a lower performance IQ in contrast to a within-normal verbal IQ in TS individuals . The presence of hypogonadism with normal or may be elevated adrenal function in girls with turner syndrome provide a model to study the hormonal effect of adrenal androgen in absence of estrogen on gender-role behavior. Ehrhardt et al (1970) reported that Women with TS are described as clearly feminine in their behavior and interests . To the best of our knowledge, there have been no previous studies on the correlation between level of adrenal androgen and gender-typed behavior in Girls with TS.

Conditions

Turner Syndrome

Outcome Measures

Primary Outcomes (7)

• Serum dehydroepiandrosterone sulfate (DHEAS)

  we use DHEAS level to access adrenal function

  Baseline

• follicle stimulating hormone (FSH)

  to access ovarian function

  Baseline

• luteinizing hormone (LH)

  to access ovarian function

  Baseline

• estradiol (E2)

  to access ovarian function

  Baseline

• Gender-typed behavior

  we will measure children's gender-typed behavior using the Pre school Activities Inventory

  Baseline

• Gender-typed behavior The Children's Sex Role Inventory

  we will measure children's gender-typed behavior using The Children's Sex Role Inventory

  Baseline

• Parent-Report Gender Identity Questionnaire

  we will measure children's gender-typed behavior using the Parent-Report Gender Identity Questionnaire

  Baseline

Study Arms (2)

turner syndrome group

Diagnostic Test: the correlation between level of adrenal androgen and gender-typed behavior in Girls with TS

control group

Diagnostic Test: the correlation between level of adrenal androgen and gender-typed behavior in Girls with TS

Interventions

the correlation between level of adrenal androgen and gender-typed behavior in Girls with TS DIAGNOSTIC_TEST

Laboratory assessment Serum dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) will be measured using an enzyme mediated chemiluminescence for all participants Gender-typed behavior assessment * Parents of girls aged two to six years will evaluate their children's gender-typed behavior using the Pre school Activities Inventory * For girls above 6 years gender characteristics and gender role behavior will be evaluated using The Children's Sex Role Inventory (Child-adapted version of the original Bem Sex Role Inventory) * For all participants a Parent-Report Gender Identity Questionnaire for Children will be used to evaluate gender role behavior

control group; turner syndrome group

Eligibility Criteria

• Age: Up to 18 Years
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Girls with turner syndrome (TS) (karyotype 45, X) younger than 18 years of age and Tanner stage matched healthy control girls with normal karyotype attending outpatient clinic at Sohag University Hospital will be included in the study

You may qualify if:

• Girls with turner syndrome (TS) (karyotype 45, X) younger than 18 years of age and Tanner stage matched healthy control girls with normal karyotype attending outpatient clinic at Sohag University Hospital will be included in the study.

You may not qualify if:

• failure to obtain informed consent

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Sohag University Hospital

Sohag, Egypt

Location

Related Publications (7)

• Li M, Zhao C, Xie S, Liu X, Zhao Q, Zhang Z, Gong G. Effects of hypogonadism on brain development during adolescence in girls with Turner syndrome. Hum Brain Mapp. 2019 Dec 1;40(17):4901-4911. doi: 10.1002/hbm.24745. Epub 2019 Aug 7.

  PMID: 31389646 BACKGROUND

• Counts DR, Pescovitz OH, Barnes KM, Hench KD, Chrousos GP, Sherins RJ, Comite F, Loriaux DL, Cutler GB Jr. Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1987 Jun;64(6):1174-8. doi: 10.1210/jcem-64-6-1174.

  PMID: 3571422 BACKGROUND

• Zhao C, Gong G. Mapping the effect of the X chromosome on the human brain: Neuroimaging evidence from Turner syndrome. Neurosci Biobehav Rev. 2017 Sep;80:263-275. doi: 10.1016/j.neubiorev.2017.05.023. Epub 2017 Jun 4.

  PMID: 28591595 BACKGROUND

• Ehrhardt AA, Greenberg N, Money J. Female gender identity and absence of fetal gonadal hormones: Turner's syndrome. Johns Hopkins Med J. 1970 May;126(5):237-48. No abstract available.

  PMID: 4911705 BACKGROUND

• Mueller SC. Magnetic resonance imaging in paediatric psychoneuroendocrinology: a new frontier for understanding the impact of hormones on emotion and cognition. J Neuroendocrinol. 2013 Aug;25(8):762-70. doi: 10.1111/jne.12048.

  PMID: 23656557 BACKGROUND

• Johnson LL, Bradley SJ, Birkenfeld-Adams AS, Kuksis MA, Maing DM, Mitchell JN, Zucker KJ. A parent-report gender identity questionnaire for children. Arch Sex Behav. 2004 Apr;33(2):105-16. doi: 10.1023/b:aseb.0000014325.68094.f3.

  PMID: 15146143 BACKGROUND

• Dorr HG, Penger T, Marx M, Rauh M, Oppelt PG, Volkl TKM. Adrenarche and pubarche in girls with turner syndrome during growth-promoting therapy with human growth hormone. BMC Endocr Disord. 2019 Jan 18;19(1):9. doi: 10.1186/s12902-019-0333-z.

  PMID: 30658614 BACKGROUND

MeSH Terms

Conditions

Turner Syndrome

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: resident doctor at pediatric department

Study Record Dates

• First Submitted: April 17, 2022
• First Posted: April 26, 2022
• Study Start: May 1, 2022
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

EG (1)