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Review
. 2025 Apr;4(4):101650.
doi: 10.1016/j.jacadv.2025.101650. Epub 2025 Mar 14.

Sex Hormones and Heart Failure Risk

Imo A Ebong  1 , Duke Appiah  2 , Rina Mauricio  3 , Nikhil Narang  4 , Michael C Honigberg  5 , Onyedika J Ilonze  6 , Niti R Aggarwal  7 , Markella V Zanni  8 , Selma F Mohammed  9 , Leslie Cho  10 , Erin D Michos  11 ; American College of Cardiology Cardiovascular Disease in Women Committee
Affiliations
Review

Sex Hormones and Heart Failure Risk

Imo A Ebong et al. JACC Adv. 2025 Apr.

Abstract

Heart failure (HF) is a significant cause of morbidity and mortality. Although there are inconsistencies, epidemiological studies have implicated sex hormones (SHs) in pathways that are linked to HF. The age-related decline in SH levels causes physiological changes that differentially impact HF risk in both sexes. Conversely, SHs are tightly regulated by complex feedback loops that become disrupted in chronic HF to create a vicious cycle that further worsens the HF syndrome. By altering the androgenic balance, SHs exert variable effects that could impact HF risk in men and women. Further studies are needed to clarify whether measurement of SH levels can identify future HF patients for early intervention, as well as HF patients who may benefit from more intensive treatments.

Keywords: androgens; estrogen; heart failure; sex hormones; testosterone.

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Conflict of interest statement

Funding support and author disclosures Dr Ebong is supported by R21 HL165018-01 and U01 HL160274 grants from the NHLBI, and the American Heart Association Strategically Focused Research Network grant 23SFRNPCS1064232. Dr Honigberg is supported by the NHLBI (K08HL166687), the American Heart Association (940166, 24RGRSG1275749), and PCORI. Dr Michos is supported by American Heart Association grants 946222 and 20SFRN35120152, as well as the Amato Fund in Women’s Cardiovascular Health Research by Johns Hopkins University. Dr Ebong has received consulting fees from Alexion Pharmaceuticals. Dr Honigberg has received consulting fees from Comanche Biopharma; advisory board service for Miga Health; site principal investigator work for Novartis; and research support from Genentech. Dr Narang has received speaker fees from Boehringer Ingelheim, AstraZeneca, and BridgeBio. Dr Ilonze has received consulting fees from Bristol Myers Squibb and AstraZeneca. Dr Michos has received consulting fees from Amgen, Arrowhead, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, Esperion, Ionis, Eli Lilly, Medtronic, Merck, New Amsterdam, Novartis, Novo Nordisk, and Zoll.

Figures

None
Graphical abstract
Figure 1
Figure 1
Mechanism of Estrogen and Androgens in Regulating Myocardial Gene Expression By binding to cell-specific receptors, sex hormones modulate genomic and nongenomic activity that regulate myocardial function. ↑↑ = promotes; AR = androgen receptor; Ca++ = calcium; ER = estrogen receptor; ERK = extracellular signal-regulated kinase; GPER = G-protein-coupled estrogen receptor; K+ = potassium; MAPK = mitogen-activated protein kinase.
Central Illustration
Central Illustration
Beneficial Actions of Sex Hormones on Cardiac Function At physiological concentrations, sex hormones have cardioprotective effects in both sexes. ↓↓ = inhibits; ↑↑ = promotes; DHEA = dehydroepiandrosterone.
Figure 2
Figure 2
Bidirectional Relationship Between Sex Hormones and Heart Failure Heart failure causes metabolic changes that dysregulate sex hormonal equilibrium thereby creating a vicious cycle.
Figure 3
Figure 3
Challenges to Use of Sex Hormones for Heart Failure Risk Stratification Sex hormones could improve heart failure risk stratification when considered concurrently with traditional risk markers.
See this image and copyright information in PMC

References

    1. Martin S.S., Aday A.W., Almarzooq Z.I., et al. 2024 heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2024;149(8):e347–e913. doi: 10.1161/cir.0000000000001209. - DOI - PubMed
    1. Zhao D., Guallar E., Ballantyne C.M., et al. Sex hormones and incident heart failure in men and postmenopausal women: the Atherosclerosis Risk in Communities study. J Clin Endocrinol Metab. 2020;105(10):e3798–e3807. doi: 10.1210/clinem/dgaa500. - DOI - PMC - PubMed
    1. Zhao D., Guallar E., Ouyang P., et al. Endogenous sex hormones and incident cardiovascular disease in post-menopausal women. J Am Coll Cardiol. 2018;71(22):2555–2566. doi: 10.1016/j.jacc.2018.01.083. - DOI - PMC - PubMed
    1. Kim C., Wellons M. Sex hormones and cardiovascular disease in relation to menopause. Endocrinol Metab Clin North Am. 2023;52(2):195–210. doi: 10.1016/j.ecl.2022.10.005. - DOI - PubMed
    1. Chehab O., Shabani M., Varadarajan V., et al. Endogenous sex hormone levels and myocardial fibrosis in men and postmenopausal women. JACC Adv. 2023;2(3) doi: 10.1016/j.jacadv.2023.100320. - DOI - PMC - PubMed