Heart Failure Reviews

, Volume 24, Issue 6, pp 915–925 | Cite as

Sex differences in anthracycline-induced cardiotoxicity: the benefits of estrogens

  • Christian Cadeddu Dessalvi
  • Alessia Pepe
  • Claudia Penna
  • Alessia Gimelli
  • Rosalinda Madonna
  • Donato Mele
  • Ines Monte
  • Giuseppina Novo
  • Cinzia Nugara
  • Concetta Zito
  • Javid J Moslehi
  • Rudolf A de Boer
  • Alexander R. Lyon
  • Carlo Gabriele TocchettiEmail author
  • Giuseppe Mercuro


Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.


Anthracycline cardiotoxicity Gender differences Pathophysiology, monitoring, and protection from anthracycline cardiotoxicity 



Carlo Gabriele Tocchetti is funded by a Federico II University/Ricerca di Ateneo grant. Rudolf A de Boer is supported by the Netherlands Heart Foundation (CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11); and the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350).

Compliance with ethical standards

Conflict of interest

Carlo Gabriele Tocchetti received speaking fees from Alere; Rudolf A de Boer: the UMCG, which employs RAdB, has received research grants and/or fees from AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Roche, Trevena, and ThermoFisher GmbH. RAdB is a minority shareholder of scPharmaceuticals, Inc. RAdB received personal fees from MandalMed Inc., AstraZeneca, Novartis, Servier, and Vifor. Alexander R. Lyon has received speaker, advisory board or consultancy fees, and/or research grants from Pfizer, Novartis, Servier, Amgen, Clinigen Group, Takeda, Roche, Eisai Ltd., Eli Lily, and Boehringer Ingelheim. Javid Moslehi has served as a consultant/advisor for Novartis, Pfizer, Bristol-Myers Squibb, Takeda/Millennium, Ariad, Acceleron, Vertex, Incyte, Rgenix, Verastem, Pharmacyclics, StemCentRx, Heat Biologics, Daiichi-Sankyo, and Regeneron. All other authors have no conflicts of interest or financial ties to disclose.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Christian Cadeddu Dessalvi
    • 1
  • Alessia Pepe
    • 2
  • Claudia Penna
    • 3
  • Alessia Gimelli
    • 4
  • Rosalinda Madonna
    • 5
  • Donato Mele
    • 6
  • Ines Monte
    • 7
  • Giuseppina Novo
    • 8
  • Cinzia Nugara
    • 8
  • Concetta Zito
    • 9
  • Javid J Moslehi
    • 10
  • Rudolf A de Boer
    • 11
  • Alexander R. Lyon
    • 12
  • Carlo Gabriele Tocchetti
    • 13
    • 14
    Email author
  • Giuseppe Mercuro
    • 1
  1. 1.Department of Medical Sciences and Public HealthUniversity of CagliariCagliariItaly
  2. 2.Magnetic Resonance Imaging UnitFondazione G. Monasterio C.N.R.- Regione ToscanaPisaItaly
  3. 3.Department of Clinical and Biological SciencesUniversity of TurinTurinItaly
  4. 4.Nuclear Medicine UnitFondazione G. Monasterio C.N.R.- Regione ToscanaPisaItaly
  5. 5.Center of Aging Sciences and Translational Medicine - CESI-MeT“G. d’Annunzio” UniversityChietiItaly
  6. 6.Cardiology Unit, Emergency DepartmentUniversity Hospital of FerraraFerraraItaly
  7. 7.Department of General Surgery and Medical-Surgery Specialities- CardiologyUniversity of CataniaCataniaItaly
  8. 8.Department of CardiologyUniversity of PalermoPalermoItaly
  9. 9.Department of Clinical and Experimental Medicine – CardiologyUniversity of MessinaMessinaItaly
  10. 10.Vanderbilt Ingram Cancer Center, Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  11. 11.University Medical Center Groningen, Department of CardiologyUniversity of GroningenGroningenthe Netherlands
  12. 12.Royal Brompton Hospital and Imperial College LondonLondonUK
  13. 13.Department of Translational Medical SciencesFederico II UniversityNaplesItaly
  14. 14.Interdepartmental Center for Clinical and Translational Research (CIRCET)Federico II UniversityNaplesItaly

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