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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hulley, S. (1998) · JAMA · doi:10.1001/jama.280.7.605 · Cited by 6,216 · 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].”
Doubly robust estimation in missing data and causal inference models
Bang, H., & Robins, J. M. (2005) · Biometrics · doi:10.1111/j.1541-0420.2005.00377.x · Cited by 1,998 · cited 1×
“[12] These estimates are unconfounded by the adjustment variables if the prescriptionodds model or the outcome-regression model is specified correctly.”
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
Hirano, K., & Imbens, G. W. (2001) · Health Services and Outcomes Research Methodology · doi:10.1023/a:1020371312283 · Cited by 1,039 · cited 1×
“[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.”
Adverse Effects of Testosterone Therapy in Adult Men: A Systematic Review and Meta-Analysis
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
Thrombotic stroke and myocardial infarction with hormonal contraception
Lidegaard, Ø., Løkkegaard, E., Jensen, A., Skovlund, C. W., & Keiding, N. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1111840 · Cited by 607 · 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].”
Background
Research works printed but not linked: 1
- Rothman KJ, Greenland S, Lash TL (2008) Modern epidemiology. Philadelphia, Pa.; London: Lippincott Williams & Wilkins.
Cited by
Sorted by citations
Cardiovascular Risks Associated with Gender and Aging
Rodgers, J. L., Jones, J., Bolleddu, S. I., Vanthenapalli, S., Rodgers, L. E., Shah, K., Karia, K., & Panguluri, S. K. (2019) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd6020019 · Cited by 1,153
“In a larger meta-analysis study that reported results from approximately 3000 older men, it was found that men treated with testosterone had a 54% increase in cardiovascular events, as compared with those treated with a placebo [146].”
BackgroundEffects of Testosterone Treatment in Older Men
Snyder, P. J., Bhasin, S., Cunningham, G. R., Matsumoto, A. M., Stephens-Shields, A. J., Cauley, J. A., Gill, T. M., Barrett-Connor, E., Swerdloff, R. S., Wang, C., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1506119 · Cited by 890
Yafi, F. A., Jenkins, L., Albersen, M., Corona, G., Isidori, A. M., Goldfarb, S., Maggi, M., Nelson, C. J., Parish, S., Salonia, A., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.3 · Cited by 853
Leydig cells: formation, function, and regulation†
Zirkin, B. R., & Papadopoulos, V. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy059 · Cited by 761
Sex differences in lipid and lipoprotein metabolism
Palmisano, B. T., Zhu, L., Eckel, R. H., & Stafford, J. M. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.05.008 · Cited by 551
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
