Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context
Summary: Background: Men with Klinefelter syndrome (KS) have hypogonadism, increased morbidity, and excess mortality. Testosterone replacement therapy (TRT) has the potential to alleviate this burden. We assessed the risk of major cardiovascular events (MACE) and mortality in KS according to TRT ex...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
|
| Series: | The Lancet Regional Health. Europe |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666776225000225 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832573020131033088 |
|---|---|
| author | Simon Chang Lars Pedersen Anne Skakkebæk Agnethe Berglund Claus H. Gravholt |
| author_facet | Simon Chang Lars Pedersen Anne Skakkebæk Agnethe Berglund Claus H. Gravholt |
| author_sort | Simon Chang |
| collection | DOAJ |
| description | Summary: Background: Men with Klinefelter syndrome (KS) have hypogonadism, increased morbidity, and excess mortality. Testosterone replacement therapy (TRT) has the potential to alleviate this burden. We assessed the risk of major cardiovascular events (MACE) and mortality in KS according to TRT exposure. Methods: We performed a nationwide registry based matched cohort study. We compared incidences of MACE and mortality between TRT exposed (KS-TRT) or unexposed KS (KS-non-TRT), and a male background population comparison cohort. The study period was from 1 January 1994 to 31 December 2022. Findings: We identified 557 KS-TRT, and matched these with unexposed men with KS born the same year (total KS n = 950). We similarly identified a comparison cohort of 50,150 men from the background population matched on month and year of birth. Median age at entry for KS-TRT was 31.1 years (interquartile range; 19.9–40.0) and median follow-up time was 12.9 years (interquartile range; 7.5–20.7). KS-TRT was associated with lower all-cause mortality (adjusted hazard ratio (95% CI); 0.56 (0.37–0.85)), with mortality in KS-TRT comparable to the comparison cohort (hazard ratio (95% CI); 1.27 (0.91–1.79)). Incidence of MACE was comparable between KS-TRT and KS-non-TRT. Interpretation: TRT could alleviate excess mortality in KS and appears safe regarding cardiovascular risk. Today, most men with KS go undiagnosed, missing proper medical attention. There is a dire need for a policy change to ensure timely diagnosis and treatment in all men with KS. Funding: The A.P. Moller Foundation, Fonden af 17-12-1981, Danish Diabetes and Endocrine Academy, Novo Nordisk Foundation, the Independent Research Fund Denmark, Sygesikringen danmark. |
| format | Article |
| id | doaj-art-8b4498769b9b49f9b4622652a82f562c |
| institution | Kabale University |
| issn | 2666-7762 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Regional Health. Europe |
| spelling | doaj-art-8b4498769b9b49f9b4622652a82f562c2025-02-02T05:29:25ZengElsevierThe Lancet Regional Health. Europe2666-77622025-04-0151101230Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in contextSimon Chang0Lars Pedersen1Anne Skakkebæk2Agnethe Berglund3Claus H. Gravholt4Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark; Unit for Thrombosis Research, University Hospital of Southern Denmark, Esbjerg, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Corresponding author. Brendstrupgårdsvej 21A, DK-8200, Aarhus, Denmark.Department of Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Denmark; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, DenmarkDepartment of Endocrinology, Aarhus University Hospital, Aarhus, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, DenmarkDepartment of Endocrinology, Aarhus University Hospital, Aarhus, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, DenmarkSummary: Background: Men with Klinefelter syndrome (KS) have hypogonadism, increased morbidity, and excess mortality. Testosterone replacement therapy (TRT) has the potential to alleviate this burden. We assessed the risk of major cardiovascular events (MACE) and mortality in KS according to TRT exposure. Methods: We performed a nationwide registry based matched cohort study. We compared incidences of MACE and mortality between TRT exposed (KS-TRT) or unexposed KS (KS-non-TRT), and a male background population comparison cohort. The study period was from 1 January 1994 to 31 December 2022. Findings: We identified 557 KS-TRT, and matched these with unexposed men with KS born the same year (total KS n = 950). We similarly identified a comparison cohort of 50,150 men from the background population matched on month and year of birth. Median age at entry for KS-TRT was 31.1 years (interquartile range; 19.9–40.0) and median follow-up time was 12.9 years (interquartile range; 7.5–20.7). KS-TRT was associated with lower all-cause mortality (adjusted hazard ratio (95% CI); 0.56 (0.37–0.85)), with mortality in KS-TRT comparable to the comparison cohort (hazard ratio (95% CI); 1.27 (0.91–1.79)). Incidence of MACE was comparable between KS-TRT and KS-non-TRT. Interpretation: TRT could alleviate excess mortality in KS and appears safe regarding cardiovascular risk. Today, most men with KS go undiagnosed, missing proper medical attention. There is a dire need for a policy change to ensure timely diagnosis and treatment in all men with KS. Funding: The A.P. Moller Foundation, Fonden af 17-12-1981, Danish Diabetes and Endocrine Academy, Novo Nordisk Foundation, the Independent Research Fund Denmark, Sygesikringen danmark.http://www.sciencedirect.com/science/article/pii/S2666776225000225Testosterone replacement therapyMortalityMajor cardiovasular eventsKlinefelter syndromeHypogonadism |
| spellingShingle | Simon Chang Lars Pedersen Anne Skakkebæk Agnethe Berglund Claus H. Gravholt Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context The Lancet Regional Health. Europe Testosterone replacement therapy Mortality Major cardiovasular events Klinefelter syndrome Hypogonadism |
| title | Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context |
| title_full | Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context |
| title_fullStr | Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context |
| title_full_unstemmed | Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context |
| title_short | Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort studyResearch in context |
| title_sort | cardiovascular risk and mortality in men receiving testosterone replacement therapy for klinefelter syndrome in denmark a retrospective cohort studyresearch in context |
| topic | Testosterone replacement therapy Mortality Major cardiovasular events Klinefelter syndrome Hypogonadism |
| url | http://www.sciencedirect.com/science/article/pii/S2666776225000225 |
| work_keys_str_mv | AT simonchang cardiovascularriskandmortalityinmenreceivingtestosteronereplacementtherapyforklinefeltersyndromeindenmarkaretrospectivecohortstudyresearchincontext AT larspedersen cardiovascularriskandmortalityinmenreceivingtestosteronereplacementtherapyforklinefeltersyndromeindenmarkaretrospectivecohortstudyresearchincontext AT anneskakkebæk cardiovascularriskandmortalityinmenreceivingtestosteronereplacementtherapyforklinefeltersyndromeindenmarkaretrospectivecohortstudyresearchincontext AT agnetheberglund cardiovascularriskandmortalityinmenreceivingtestosteronereplacementtherapyforklinefeltersyndromeindenmarkaretrospectivecohortstudyresearchincontext AT claushgravholt cardiovascularriskandmortalityinmenreceivingtestosteronereplacementtherapyforklinefeltersyndromeindenmarkaretrospectivecohortstudyresearchincontext |