Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen
Abstract
OBJECTIVES: Raised liver enzymes are a common feature of Turner's syndrome (TS), but the cause remains unclear. We studied the hepatic function in a large cohort of women with TS and tested the effect of increasing doses of hormone replacement therapy (HRT) on liver function tests (LFTs). DESIGN AND PATIENTS: LFTs were assessed in three studies. A cross-sectional review of liver function of 125 women (median age: 31 years), a longitudinal study of 30 women (mean follow-up period: 8 years) and a dose-response study of 14 women with TS and 11 controls with hypogonadism, who received oral 17-beta-oestradiol (E(2)) 1, 2 and 4 mg daily in a cyclical formulation for 12 weeks each. MEASUREMENTS: Clinical features, oestrogen use and metabolic parameters were compared to liver enzymes (gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), albumin and bilirubin. LFTs were also measured during each treatment interval of the dose-response study. Hepatic autoimmunity was sought in the cross-sectional study. RESULTS: When compared to the control population, as opposed to reference ranges, 91% of women with TS demonstrated liver enzyme elevation, with a yearly incidence of 2.1%. LFTs correlated positively with cholesterol (P < 0.001), BMI (P = 0.004) and type of oestrogen therapy (P = 0.04). Increasing doses of HRT resulted in a significant decrease in GGT, ALT, bilirubin and albumin. No evidence of excessive hepatic autoimmunity was found. CONCLUSION: The prevalence of raised liver enzymes in TS may have been underestimated by the use of reference ranges rather than matched controls. Obesity and hyperlipidaemia are associated with raised LFTs, as well as the use of HRT compared to the oral contraceptive pill (OCP). Exogenous oestrogen both as OCP and HRT improves liver function. Liver dysfunction in TS is likely to be a form of hepatic steatosis and intervention trials are now indicated.
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There is no evidence of liver toxicity from E2 treatment.
“No evidence of liver toxicity”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [342]
Even young children with TS without risk factors have a higher prevalence of LFA.
“Risk factors for LFA are age, obesity, insulin resistance, and Xq isochromosome, however even young children with TS without risk factors have a higher prevalence of LFA.342-344,714,715”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [342]
LFA, defined as increased liver enzymes, are present in 40%-80% of patients with TS, with more recent studies on the high end of that estimate.
“LFA, defined as increased liver enzymes are present in 40%-80% of patients with TS, with more recent studies on the high end of that estimate.342-344,714,715”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [342]
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- Authors
- Koulouri, O., Ostberg, J., & Conway, G. S.
- Affiliations
- University College Hospital (GB)
- Corresponding author
- Conway, Gerard S.
- ORCID
- Conway, Gerard S.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2008-07-15
- Volume
- 69
- Issue
- 2
- Pages
- 306-310
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W1963941815
- Cited by
- 71
- References
- 17
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 11 · 2018: 3 · 2017: 3 · 2016: 1 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- Turner syndrome, liver dysfunction, liver enzymes, hormone replacement therapy, exogenous estrogen, 17 beta-oestradiol, hepatic steatosis, obesity, hyperlipidemia, oral contraceptives, natural history (disease)
- MeSH terms
- Adolescent, Adult, Cross-Sectional Studies, Dose-Response Relationship, Drug, Female, Humans, Liver Diseases, Middle Aged, Retrospective Studies, Turner Syndrome, Cohort Studies, Estrogen Replacement Therapy, Prevalence, Estradiol Congeners, Young Adult, Chemical and Drug Induced Liver Injury
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