The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men
Open accessAbstract
BACKGROUND: An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly. METHODS: We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation. RESULTS: In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥ 75 years (p trend = 0.03), while no trend was seen for PDE5I (p trend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11). DISCUSSION: In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.
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“Some epidemiological studies have reported an increase in cardiovascular mortality related to TRT while others have not been able to establish a correlation between the two [19,20].”
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Cites
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“[26–29] The mechanisms linking estrogens to thrombotic events may be related to markers of activated coagulation, decreased coagulation inhibitors, and activated protein C resistance [30].”
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BackgroundPostmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause
Rossouw, J. E., Prentice, R. L., Manson, J. E., Wu, L., Barad, D., Barnabei, V. M., Ko, M., LaCroix, A. Z., Margolis, K. L., & Stefanick, M. L. (2007) · JAMA · doi:10.1001/jama.297.13.1465 · Cited by 1,741 · cited 1×
“[26–29] The mechanisms linking estrogens to thrombotic events may be related to markers of activated coagulation, decreased coagulation inhibitors, and activated protein C resistance [30].”
BackgroundAdverse Events Associated with Testosterone Administration
Basaria, S., Coviello, A. D., Travison, T. G., Storer, T. W., Farwell, W. R., Jette, A. M., Eder, R., Tennstedt, S., Ulloor, J., Zhang, A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000485 · Cited by 1,494 · cited 3×
“[4] This was followed by a meta-analysis of a number of a number of very small trials in predominantly older men which also suggested excess cardiovascular risk.”
BackgroundMethodMajor Risk Factors as Antecedents of Fatal and Nonfatal Coronary Heart Disease Events
Greenland, P. (2003) · JAMA · doi:10.1001/jama.290.7.891 · Cited by 1,053
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“[11] This weighting aligns the distribution in the comparison cohort of the variables used in the prescription-probability model to match the distribution in the TT prescription cohort.”
MethodVigen, R. (2013) · JAMA · doi:10.1001/jama.2013.280386 · Cited by 1,003 · cited 1×
“[6] In the two studies assessing timing of the increase, it was noted to appear very soon following initiation of therapy.”
BackgroundCardiovascular Events and Intensity of Treatment in Polycythemia Vera
Marchioli, R., Finazzi, G., Specchia, G., Cacciola, R. R., Cavazzina, R., Cilloni, D., Stefano, V. D., Elli, E. M., Iurlo, A., Latagliata, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1208500 · Cited by 871 · cited 1×
“Exogenous testosterone (TT) is associated with physiologic changes that predispose to clotting and thrombotic disorders including increased blood pressure [18], polycythemia [19], reductions in HDL cholesterol [18,20], and hyperviscosity of the blood and platelet aggregation.”
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Fernández-Balsells, M. M., Murad, M. H., Lane, M., Lampropulos, J. F., Albuquerque, F., Mullan, R. J., Agrwal, N., Elamin, M. B., Gallegos-Orozco, J. F., Wang, A. T., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2575 · Cited by 713
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“[26–29] The mechanisms linking estrogens to thrombotic events may be related to markers of activated coagulation, decreased coagulation inhibitors, and activated protein C resistance [30].”
Background
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Funktioneller Hypogonadismus: Diabetes mellitus, Adipositas, metabolisches Syndrom und Testosteron
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Metadata
- Authors
- Finkle, W. D., Greenland, S., Ridgeway, G. K., Adams, J. L., Frasco, M. A., Cook, M. B., Fraumeni, J. F., & Hoover, R. N.
- Affiliations
- University of California, Los Angeles (US)
- National Cancer Institute (US)
- Corresponding author
- Finkle, William D.
- Hoover, Robert N.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-01-29
- Volume
- 9
- Issue
- 1
- Pages
- e85805
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3905977
- OpenAlex
- W2156204904
- Cited by
- 735
- References
- 31
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 33 · 2023: 42 · 2022: 45 · 2021: 32 · 2020: 41 · 2019: 52 · 2018: 69 · 2017: 87 · 2016: 79 · 2015: 112 · 2014: 86
- FWCI
- 97.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, public-domain)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- testosterone replacement therapy, myocardial infarction, cardiovascular risk, phosphodiesterase-5 inhibitors, sildenafil, tadalafil, men, older men, heart disease history, drug safety, adverse drug reactions
- MeSH terms
- Tadalafil, Sildenafil Citrate, Age Factors, Aged, Carbolines, Humans, Male, Middle Aged, Myocardial Infarction, Piperazines, Purines, Risk, Sulfones, Testosterone, Prescription Drugs, Phosphodiesterase 5 Inhibitors
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