Need for standardising adverse event reporting in testosterone trials

Basaria, Shehzad

doi:10.1136/eb-2013-101402

Cited by 6 publications

(5 citation statements)

References 7 publications

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“…It has also been suggested that the decrease in testosterone among older men may represent aggregative long-term effects of multiple age-related co-morbid conditions on the hypothalamic-pituitary-gonadal (HPG) axis, rather than aging per se 11 . However, our data argue against his explanation because when we adjusted for multiple comorbidities 27 , including smoking status, HCV-co-infection, history of diabetes, cumulative years on HAART for HIV-infected participants, diabetes mellitus, depression, hypertension, kidney disease, liver disease and cancer within a year, the effect of age on changes in FT was unaltered.…”

Section: Discussionmentioning

confidence: 57%

Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men

Slama

Jacobson

Li³

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Aging in males is associated with lower testosterone levels and a decrease in diurnal variation of testosterone secretion. Cross-sectional studies have shown lower than expected testosterone levels among HIV-infected men, but whether age-related changes in serum testosterone differ by HIV serostatus is not known. Methods HIV-infected men from the Multicenter AIDS Cohort Study (MACS), age ≥ 45 years at highly active antiretroviral therapy initiation, who had ≥ 2 samples from the subsequent 10 years, were matched to HIV-uninfected men by age, race, MACS site, and calendar time of samples. Linear mixed effects regression models were used to determine whether free testosterone (FT) and its rate of change differed by HIV serostatus. Results 182 HIV-infected and 267 HIV-uninfected men were included: median age 48.8 years (Interquartile range (IQR); 45.8, 53.4), median numbers of FT measurements per participant 4 (IQR; 3, 5), 65% were drawn in the AM. Mean adjusted FT levels were lower among HIV-infected than HIV-uninfected men in AM samples (−6.1 ng/dL (95% CI: −9.8, −2.4), p=0.001), but not in PM samples (−1.7 ng/dL (−6.0, 2.6), p=0.441). The rate of FT decline with age did not differ by HIV serostatus: 9.2 ng/dL (95% CI: −13.4, −5.0) per 10 years for HIV- infected vs. 7.9 ng/dL (95% CI: −10.2, −5.5) for HIV-uninfected men, p = 0.578. Conclusion FT decreased similarly with increasing age regardless of HIV serostatus. The lower AM, but not PM, FT levels among HIV-infected men compared to HIV-uninfected men suggests a loss of diurnal variation in FT among HIV-infected men.

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Section: Discussionmentioning

confidence: 57%

Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men

Slama

Jacobson

Li³

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…17 Currently, there is widespread debate regarding the extent to which methodological issues—such as participant eligibility criteria, disease classification, and statistical analysis methods—have contributed to the contrasting findings observed across the clinical trials, observational cohort studies, and meta-analyses that have examined testosterone use and cardiovascular risk. 21–24 …”

Section: Discussionmentioning

confidence: 99%

“…17 Currently, there is widespread debate regarding the extent to which methodological issues-such as participant eligibility criteria, disease classification, and statistical analysis methods-have contributed to the contrasting findings observed across the clinical trials, observational cohort studies, and meta-analyses that have examined testosterone use and cardiovascular risk. [21][22][23][24] The association between testosterone therapy and cardiovascular disease is complex. There are a number of physiological pathways by which testosterone therapy may either increase or decrease the risk of adverse cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy

et al. 2014

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Background Testosterone therapy for older men has increased substantially over the past decade. Research on the effects of testosterone therapy on cardiovascular outcomes has yielded inconsistent results. Objective To examine the risk of myocardial infarction (MI) in a population-based cohort of older men receiving intramuscular testosterone. Method Using a 5% national sample of Medicare beneficiaries, we identified 6355 patients treated with at least 1 injection of testosterone between January 1, 1997, and December 31, 2005. We matched this cohort to 19 065 testosterone nonusers at a 1:3 ratio based on a composite MI prognostic score. Patients were followed until December 31, 2005, or until they lost coverage from Medicare, enrolled in a health maintenance organization, experienced a MI, or died. Result In a Cox regression analysis adjusting for demographic and clinical characteristics, receipt of testosterone therapy was not associated with an increased risk of MI (hazard ratio [HR] = 0.84; 95% CI = 0.69–1.02). In this analysis, there was an interaction between receipt of testosterone and quartile of risk of MI (P = 0.023). For men in the highest quartile of the MI prognostic score, testosterone therapy was associated with a reduced risk of MI (HR = 0.69; 95% CI = 0.53–0.92), whereas there was no difference in risk for the first (HR = 1.20; 95% CI = 0.88–1.67), second (HR = 0.94; 95% CI = 0.69–1.30), and third quartiles (HR = 0.78; 95% CI = 0.59–1.01). Conclusion Older men who were treated with intramuscular testosterone did not appear to have an increased risk of MI. For men with high MI risk, testosterone use was modestly protective against MI.

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“…Furthermore, the recording and reporting of adverse events in previous testosterone trials have not followed a standardized format, underscoring the need for standardization of adverse event reporting in future trials. 56 …”

Section: Cardiovascular Events In Clinical Trials Of Testosterone Repmentioning

confidence: 99%

Trials of testosterone replacement reporting cardiovascular adverse events

Gagliano‐Jucá

Basaria

2018

Asian J Androl

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The numbers of testosterone prescriptions written have increased several-fold worldwide, but the incidence of pathological hypogonadism due to hypothalamic, pituitary, and testicular disease has remained unchanged. Most of these prescriptions are being dispensed to middle-aged and older men who have experienced age-related decline in serum testosterone levels; a subset of the population in which benefits of testosterone replacement is at best, modest. Recently, some randomized controlled trials have reported increased cardiovascular events in men (mainly older men and those with prevalent cardiovascular disease) with testosterone use, and a few recent meta-analyses have confirmed these findings. In this review, we discuss trials of testosterone therapy that have reported higher cardiovascular events, relevant trials that have not reported increased cardiovascular events and large trials that have focused on cardiovascular risk (mainly atherosclerosis progression) as their main outcome. We also review findings from meta-analyses that have evaluated cardiovascular events in various testosterone trials. Finally, we discuss some potential mechanisms by which testosterone use might result in an increased cardiovascular risk. As none of the trials conducted to date were adequately powered to evaluate cardiovascular events, no firm conclusions can be drawn regarding the cardiovascular safety of testosterone therapy at this time. In the interim, we hope that this review will help practitioners make informed decisions regarding the care of their patients.

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Need for standardising adverse event reporting in testosterone trials

Cited by 6 publications

References 7 publications

Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men

Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men

Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy

Trials of testosterone replacement reporting cardiovascular adverse events

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