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Quantitative Liver Functions in Turner Syndrome With and Without Hormone Replacement Therapy

This study has been completed.
Sponsor:
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00825617
First received: January 20, 2009
Last updated: NA
Last verified: January 2009
History: No changes posted
  Purpose

Several studies have demonstrated that Turner Syndrome patients have elevated liver enzymes readily suppressible by a short course of HRT. We wanted to estimated quantitative liver functions in a young group of Turner syndrome patients compared to a healthy control group.


Condition Intervention
Turner Syndrome
Drug: Hormone replacement therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Quantitative Liver Functions in Turner Syndrome With and Without Hormone Replacement Therapy

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • quantitative liver function tests [ Time Frame: 1996-1999 ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: October 1996
Study Completion Date: June 2000
Primary Completion Date: October 1999 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HRT
Women with TS were treated with oral hormone substitution consisting of 2 mg 17β-estradiol/day for days 1-12, 2 mg 17β-estradiol/day and 1 mg norethisterone acetate/day for days 13-22 and 1 mg 17β-estradiol/day for days 23-28 (Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark)
Drug: Hormone replacement therapy
Women with TS were treated with oral hormone substitution consisting of 2 mg 17β-estradiol/day for days 1-12, 2 mg 17β-estradiol/day and 1 mg norethisterone acetate/day for days 13-22 and 1 mg 17β-estradiol/day for days 23-28 (Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark)
Other Name: Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark

Detailed Description:

Turner syndrome is due to the absence of a part of or the entire X chromosome in females. Stature is short, and morbidity is increased due to risk of osteoporosis and fractures, type 2 diabetes, ischemic heart disease, hypertension, and stroke, but also the risk of cirrhosis is increased. Clinical studies have shown a frequent occurrence of elevated liver enzymes, primarily alanine aminotransferase, g-glutamyl-transferase, and alkaline phosphatase, while bilirubin is normal.

We and others have shown a normalizing effect of hormone replacement therapy (HRT), containing 17bestradiol and a gestagen, on liver enzymes, which may point towards a protective effect on hepatocyte integrity. Marked architectural changes, including nodular regenerative hyperplasia, multiple focal nodular hyperplasia and cirrhosis are observed in some patients and are associated with a risk of liver-related complications. These changes are frequently associated with vascular disorders such as obliterative portal venopathy, probably related to congenitally abnormal vessels. Steatosis, steatofibrosis, and steatohepatitis are seen and may be caused by metabolic disorders. In addition, bile duct alterations resembling small duct sclerosing cholangitis are observed in several patients. Presently, it is not known whether these perturbations in liver morphology and in liver-derived enzymes are related to functional defects in females with TS and whether this may change by HRT. To further explore quantitative liver function in TS, we examined adult women with TS on and off HRT and compared them with a control group of age matched normal women. We used the galactose elimination capacity to assess hepatocyte cytosol activity, the plasma clearance of indocyanine green to assess hepatic blood flow and excretory liver cell function independently of hepatic blood flow, the antipyrine plasma clearance to estimate hepatic microsomal system activity, and the functional hepatic nitrogen clearance to assess mitochondrial- cytosolic metabolic capacity for conversion of amino-nitrogen.We assumed that one or more these metabolic liver functions would be diminished in untreated TS and normalized by HRT. Our principal objective was to understand mechanistically how HRT improves liver function in TS.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Turner syndrome by karyotype

Exclusion Criteria:

  • Thyroid abnormality
  • Glucocorticoid treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00825617

Locations
Denmark
Medical department M and Investigational Laboratories
Aarhus C, Jutland, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: J S Christíansen, Professor Medical departmnet M, Aarhus University Hospital, NBG, Denamrk,
  More Information

No publications provided

Responsible Party: MD, PhD, DMSc Claus H. Gravholt, Medical department M, Aarhus University Hospital, Denmark
ClinicalTrials.gov Identifier: NCT00825617     History of Changes
Other Study ID Numbers: 19963561
Study First Received: January 20, 2009
Last Updated: January 20, 2009
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee

Keywords provided by University of Aarhus:
TS
HRT
Liver function tests

Additional relevant MeSH terms:
Gonadal Dysgenesis
Primary Ovarian Insufficiency
Syndrome
Turner Syndrome
Adnexal Diseases
Cardiovascular Abnormalities
Cardiovascular Diseases
Chromosome Disorders
Congenital Abnormalities
Disease
Disorders of Sex Development
Endocrine System Diseases
Genetic Diseases, Inborn
Genital Diseases, Female
Gonadal Disorders
Heart Defects, Congenital
Heart Diseases
Ovarian Diseases
Pathologic Processes
Sex Chromosome Disorders
Sex Chromosome Disorders of Sex Development
Urogenital Abnormalities
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014