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Testosterone and Cardiovascular Risk: Meta-Analysis of Interventional Studies
Abstract
Background: The relationship between testosterone (T) and cardiovascular (CV) risk in men is conflicting. Aim: To verify whether T therapy (TTh) represents a possible risk factor for CV morbidity and mortality. Methods: We conducted a random effect meta-analysis considering all available data from pharmaco-epidemiological studies as well as randomized placebo-controlled trials (RCTs). Outcomes: CV mortality and morbidity were investigated. Results: After screening, 15 pharmaco-epidemiological and 93 RCT studies were considered. The analysis of pharmaco-epidemiological studies documented that TTh reduces overall mortality and CV morbidity. Conversely, in RCTs, TTh had no clear effect, either beneficial or detrimental, on the incidence of CV events. However, a protective role of TTh on CV morbidity was observed when studies enrolling obese (body mass index >30 kg/m2) patients were scrutinized (Mantel-Haenszel odds ratio 0.51 [95% CI 0.27–0.96]; P = .04), although this association disappeared when only high-quality RCTs were considered (Mantel-Haenszel odds ratio 0.64 [95% CI 0.22–1.88]; P = .42). Finally, an increased risk of CV diseases was observed in RCTs when T preparations were prescribed at dosages above those normally recommended, or when frail men were considered. Clinical Implications: Pharmaco-epidemiological studies showed that TTh might reduce CV risk, but this effect was not confirmed when RCTs were considered. Strengths & Limitations: Meta-analysis of pharmaco-epidemiological studies indicates that TTh reduces overall mortality and CV morbidity. In addition, even in RCTs, a protective role of TTh on CV morbidity was envisaged when studies enrolling obese (body mass index >30 kg/m2) patients were considered. Pharmaco-epidemiological studies should be considered with caution due to the lack of completeness of follow-up and of the management of missing data. In addition, properly powered placebo-controlled RCTs with a primary CV end point, in men with late-onset hypo-gonadism, are not yet available. Finally, the duration of all studies evaluated in the present meta-analysis is relatively short, reaching a maximum of 3 years. Conclusions: Data from RCTs suggest that treatment with T is not effective in reducing CV risk, however, when TTh is correctly applied, it is not associated with an increase in CV risk and it may have a beneficial effect in some sub-populations.
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“Though testosterone therapy improves bone mineral density, lean body mass, erectile function, and anemia, there is inconclusive evidence on the benefits of testosterone therapy on cognitive function, energy levels, blood glucose or lipid levels, and controversy remains around whether testosterone therapy affects the risk of cardiovascular events (6-13).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [13]
In the citing paper
“Though testosterone therapy improves bone mineral density, lean body mass, erectile function, and anemia, there is inconclusive evidence on the benefits of testosterone therapy on cognitive function, energy levels, blood glucose or lipid levels, and controversy remains around whether testosterone therapy affects the risk of cardiovascular events (6-13).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [13]
In the citing paper
“Though testosterone therapy improves bone mineral density, lean body mass, erectile function, and anemia, there is inconclusive evidence on the benefits of testosterone therapy on cognitive function, energy levels, blood glucose or lipid levels, and controversy remains around whether testosterone therapy affects the risk of cardiovascular events (6-13).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [13]
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Metadata
- Authors
- Corona, G., Rastrelli, G., Di Pasquale, G., Sforza, A., Mannucci, E., & Maggi, M.
- Affiliations
- Azienda USL di Bologna (IT)
- University of Florence (IT)
- Cardiology Unit , Bologna, Italy
- Azienda Ospedaliero-Universitaria Careggi (IT)
- Corresponding author
- Maggi, Mario
- Venue
- The Journal of Sexual Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-06-01
- Volume
- 15
- Issue
- 6
- Pages
- 820-838
- ISSN
- 1743-6095 (ISSN-L)
- 1743-6109
- OpenAlex
- W2803859106
- Cited by
- 138
- References
- 158
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 22 · 2023: 19 · 2022: 21 · 2021: 15 · 2020: 22 · 2019: 13 · 2018: 5
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Journal of Sexual Medicine (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- testosterone replacement therapy, cardiovascular risk, cardiovascular mortality, cardiovascular morbidity, andropause, obesity, randomized controlled trials, men's health, study quality bias, publication bias
- MeSH terms
- Androgens, Cardiovascular Diseases, Humans, Hypogonadism, Male, Risk Factors, Testosterone, Body Mass Index, Randomized Controlled Trials as Topic, Hormone Replacement Therapy
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