Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy

Viuff, Mette; Stochholm, Kirstine; Lin, Angela E.; Berglund, Agnethe; Juul, Svend; Gravholt, Claus Højbjerg

doi:10.1530/eje-20-0702

Cited by 28 publications

(41 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This registry contains information on all karyotypes performed in Denmark since 1960. We have previously presented endocrine, cardiovascular and cancer data from this population 12,13 . Statistics Denmark randomly identified 100 age‐matched female controls per Turner syndrome individual from the background population (n = 115 577) and linked them with data from the following registries.…”

Section: Methodsmentioning

confidence: 99%

Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome – a nationwide cohort study

Viuff

Stochholm

Grønbæk

et al. 2021

Aliment Pharmacol Ther

View full text Add to dashboard Cite

SummaryBackgroundLiver and gastrointestinal diseases are frequent in women with Turner syndrome. However, their association with bleeding disorders, anaemia and the impact of hormone replacement therapy is unknown.AimsTo investigate the risk of liver and gastrointestinal diseases, haemorrhage and anaemia in women with Turner syndrome compared with the female background population, and the long‐term impact of hormone replacement therapy on these conditions.MethodsOne thousand one hundred and fifty‐six women with Turner syndrome diagnosed during 1960‐2014 were identified using the Danish Cytogenetic Central Registry and linked with personal‐level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115 577 age‐matched female controls. Negative binomial regression was used to analyse hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression.ResultsLiver disease increased 13‐fold (IRR 12.9 (95% CI 5.8‐28.8)), due to toxic liver disease (IRR 8.0 (95% CI 1.8‐35.4)), liver insufficiency (IRR 6.7 (95% CI 1.7‐26.9)), fibrosis/cirrhosis (IRR 16.5 (95% CI 2.2‐122.1)) and unspecified liver disease (IRR 10.6 (95% CI 4.4‐25.3)). Furthermore, presence of abnormal liver enzymes increased 12‐fold (IRR 12.4 (95% CI 4.2‐36.6)). The risk of gastrointestinal haemorrhage (IRR 3.4 (95% CI 1.8‐6.2)), anaemia (IRR 3.2 (95% CI 2.0‐5.0)) and coagulation disorders (IRR 2.9 (95% CI 1.1‐7.1)) was increased. However these diagnoses were not associated with inflammatory bowel disease. Gastrointestinal mortality was increased three‐fold (HR 3.1 (95% CI 1.5‐6.2)), partly due to death by liver disease (HR 3.0 (95% CI 1.1‐8.2)), gastrointestinal haemorrhage (HR 29.6 (95% CI 3.1‐285.1)) and capillary malformations (HR 18.6 (95% CI 4.1‐85.0)). There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases.ConclusionsThe risk of being diagnosed with liver disease was higher than previously reported. The occurrence of gastrointestinal haemorrhage and anaemia was increased in Turner syndrome. There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases was detected.

show abstract

Section: Methodsmentioning

confidence: 99%

Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome – a nationwide cohort study

Viuff

Stochholm

Grønbæk

et al. 2021

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…This leads to susceptibility of DSD-patients to many other non-GCT types of cancer that go beyond reproductive tissues e.g. solid tumors of skin and central neural system (31)(32)(33). These cellular stress phenotypes were previously described in a context of genomic instability and aneuploidy in general (27,34,35).…”

Section: Introductionmentioning

confidence: 89%

Genomic instability in patients with sex determination defects and germ cell cancer

Krivega

Zimmer

Slezko

et al. 2022

Preprint

View full text Add to dashboard Cite

The ability to transmit genetic information through generations depends on preservation of genome integrity. Genetic abnormalities affect cell differentiation, causing tissue specification defects and cancer. We addressed genomic instability in individuals with Differences of Sex Development (DSD), characterized by gonadal dysgenesis, infertility, high susceptibility for different types of cancer, especially Germ Cell Tumors (GCT), and in men with testicular GCTs. Whole proteome analysis of leukocytes, supported by specific gene expression assessment, and dysgenic gonads characterization, uncovered DNA damage phenotypes with altered innate immune response and autophagy. Further examination of DNA damage response revealed a reliance on deltaTP53, which was compromised by mutations in the transactivation domain in DSD-patients with GCT. Accordingly, drug-induced rescue of DNA damage was achieved by autophagy inhibition but not by stabilization of TP53 in DSD-patients blood in vitro. This study elucidates possibilities for prophylactic treatments of DSD patients as well as new diagnostic approaches of GCT.

show abstract

“…In TS, the long-term risk of breast cancer after longterm oral or transdermal oestrogen remains much lower than among control women (148). R 2.…”

Section: Rationalementioning

confidence: 97%

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline

Nordenström

Ahmed

Akker

et al. 2022

European Journal of Endocrinology

View full text Add to dashboard Cite

An Endo-European Reference Network (ERN) guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult, and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted and the evidence graded according to Grading of Recommendations, Assessment, Development and Evaluation system. When evidence was insufficient or lacking, conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on induction of puberty with FSH and hCG in hypogonadotrophic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommend that pubertal induction or sex hormone replacement to sustain puberty should be treated by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualized but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with a disorder of sex development or congenital pituitary deficiencies. Transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.

show abstract

Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy

Cited by 28 publications

References 27 publications

Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome – a nationwide cohort study

Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome – a nationwide cohort study

Genomic instability in patients with sex determination defects and germ cell cancer

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline

Contact Info

Product

Resources

About