Sex hormone replacement therapy in Turner syndrome—impact on morbidity and mortality
Open accessAbstract
CONTEXT: The long-term effects of female hormone replacement therapy (HRT) in Turner syndrome (TS) are unknown. OBJECTIVE: To examine morbidity, mortality and medicinal use in TS and the impact of HRT in 45,X women. DESIGN AND SETTING: National cohort study, following all TS individuals ever diagnosed in Denmark from 1977 to 2014. PATIENTS AND METHODS: In the Danish Cytogenetic Central Registry, we identified 1156 females diagnosed with TS from 1960 to 2014, and, subsequently, Statistics Denmark randomly identified 115 577 age-matched female controls. TS women and their matched controls were linked with person-level data from the National Patient Registry and the Medication Statistics Registry, and they were compared concerning mortality, hospitalizations, and medical prescriptions. Among 329 45,X women, 44 had never been HRT treated, and 285 had been treated at some point. HRT treated women were compared with untreated concerning mortality, hospitalizations, and medical prescriptions. RESULTS: Endocrine and cardiovascular mortality and morbidity were significantly increased in TS compared with the matched controls. Comparing HRT treated with nontreated 45,X women, we found a similar mortality (hazard ratio 0.83, 95% confidence interval 0.38-1.79). Among the HRT-treated 45,X women, we found a significantly lower use of antihypertensives, antidiabetics, and thyroid hormones and significantly reduced hospitalization rates for stroke and osteoporotic fractures. CONCLUSION: Women with TS have an increased overall mortality and morbidity. HRT seems to have a beneficial effect on endocrine conditions, hypertension, and stroke in women with 45,X karyotype, with no clear impact on mortality.
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Individuals with TS and a 45,X karyotype have a significantly higher frequency of comorbidities and a higher mortality compared to individuals with other TS karyotypes.
“Overall, individuals with TS and a 45,X karyotype have a significantly higher frequency of comorbidities and a higher mortality compared to individuals with other TS karyotypes.25-29”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
Up to 37% of women less than 51 years old stop their HRT prematurely.
“There are reports where up to 37% of women less than 51 years old stop their HRT prematurely.29,280,330,334”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
Dose and route of E2 do not affect glucose and insulin concentration and tolerance.
“Dose and route of E2 do not affect glucose and insulin concentration and tolerance”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
There is no sign of elevated thromboembolic risk associated with HRT in TS.
“There is no sign of elevated thromboembolic risk associated with HRT in TS”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
Coagulation is generally normal when evaluated in large TS cohorts, and in general TS does not seem to be an independent risk factor for venous thrombosis.
“Coagulation is generally normal when evaluated in large TS cohorts, and in general TS does not seem to be an independent risk factor for venous thrombosis.29”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
No evidence supports the concept that HRT increases risks for deep venous thrombosis.
“In addition, no evidence supports the concept that HRT increases risks for deep venous thrombosis.29”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
Although there is evidence suggesting that estrogen treatment can affect lipid concentrations, the impact does not seem to be clinically significant.
“Although there is evidence suggesting that estrogen treatment can affect lipid concentrations, the impact does not seem to be clinically significant.”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
The incidence of supraventricular arrhythmias, including atrial fibrillation, may be increased in individuals with TS compared to the general population.
“The incidence of supraventricular arrhythmias, including atrial fibrillation, may be increased in individuals with TS compared to the general population.29,488,489”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
Ischemic heart disease is a major cause of morbidity and mortality in TS.
“Ischemic heart disease is a major cause of morbidity and mortality in TS.27,29”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
The type or method of estrogen administration does not appear to modify cardiovascular risk.
“Additionally, the type or method of estrogen administration does not appear to modify cardiovascular risk.29”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
Individuals with TS are at an increased risk for both type 1 and type 2 diabetes.
“Individuals with TS are at an increased risk for both type 1 and type 2 diabetes.29,222,227,357,384,706”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [29]
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- Authors
- Viuff, M. H., Berglund, A., Juul, S., Andersen, N. H., Stochholm, K., & Gravholt, C. H.
- Affiliations
- Aarhus University Hospital (DK)
- Aarhus University (DK)
- Aalborg University Hospital (DK)
- Corresponding author
- Viuff, Mette H
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-09-23
- Volume
- 105
- Issue
- 2
- Pages
- 468-478
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2976117252
- Cited by
- 62
- References
- 53
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 11 · 2022: 14 · 2021: 7 · 2020: 6 · 2019: 1
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- SSRN Electronic Journal (publishedVersion)
- PubMed (publishedVersion)
- Scopus (Elsevier) (submittedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Funders
- Aarhus University
- Novo Nordisk Foundation (NNF13OC0003234, NNF15OC0016474)
- Familien Hede Nielsen foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- Turner syndrome, sex hormone replacement therapy, mortality, morbidity, 45,X karyotype, cardiovascular mortality, stroke, osteoporotic fractures, hypertension, antihypertensive medication use, hospitalization, long-term outcomes
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Child, Child, Preschool, Denmark, Endocrine System Diseases, Female, Hospitalization, Humans, Infant, Infant, Newborn, Middle Aged, Morbidity, Registries, Turner Syndrome, Hormone Replacement Therapy, Prescriptions, Young Adult
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