Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency

Cheetham, T. Craig; An, Jaejin; Jacobsen, Steven J.; Niu, Fang; Sidney, Stephen; Quesenberry, Charles P.; VanDenEeden, Stephen K.

doi:10.1001/jamainternmed.2016.9546

Cited by 148 publications

(93 citation statements)

References 39 publications

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“…Interestingly, in the T‐trials itself, there was a low and equal number of cardiovascular events in each group (7 in each arm) . Furthermore, retrospective case‐control studies have associated T prescriptions with a lower risk of CV events . This includes a large (n = 83 010) retrospective study in men with low T levels by Sharma et al in which the authors concluded there was a significant reduction in all‐cause mortality, myocardial infarction and stroke following normalization of T levels.…”

Section: Introductionmentioning

confidence: 99%

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men

Chasland

Knuiman

Divitini

et al. 2018

Clinical Endocrinology

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Objective Low endogenous sex hormones and low physical activity (PA) levels have been associated with CVD risk. Whether these interact to influence CVD outcomes remains unclear. We assessed whether sex hormone concentrations and PA were additively associated with lower central adiposity and CVD risk. Patients 3351 community‐dwelling men, mean age 77 years. Measurements Baseline testosterone (T), dihydrotestosterone (DHT) and oestradiol (E2) were assayed. Levels of PA were ascertained by questionnaire. Men were stratified using median splits into high hormone + high PA (H/H), high hormone + low PA (H/L); low hormone + high PA (L/H) and low hormone + low PA (L/L) groups. Results A total of 865 CVD events and 499 CVD deaths occurred during 10‐year mean follow‐up. Men with higher T, DHT or SHBG and higher PA had the lowest BMI, waist circumference and risk of metabolic syndrome. Men with higher T had the lowest risk of incident CVD events, irrespective of PA level. Men with higher T or DHT and higher PA had the lowest risk of dying from CVD (eg, hazard ratios for T/PA H/H 0.76 P = 0.031; H/L 0.85 P = 0.222; L/H 0.80 P = 0.075; L/L 1.00). Conclusion Higher circulating androgens and higher PA were associated with less central adiposity at baseline and fewer CVD deaths during follow‐up. These findings are consistent with a potential additive effect of androgens and PA on cardiometabolic outcomes in older men.

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Section: Introductionmentioning

confidence: 99%

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men

Chasland

Knuiman

Divitini

et al. 2018

Clinical Endocrinology

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“…First, our method for identifying AEs may not capture all relevant events. Categorizing AEs using International Classification of Diseases, Ninth Revision, Clinical Modification codes is a conservative measure 25 that has been used in prior research, 26 and the fact that these codes were verified by independent medical record reviewers other than the treating physician reduced the likelihood of systematic bias by physician specialty. Second, our cost outcome reflects the practice of applying a year-specific cost-to-charge ratio to the total charges related to the patients’ care, but this method does not account for variation in this ratio across procedures and conditions; however, it is unclear why this method would produce any bias systematically correlated with physician specialty.…”

Section: Discussionmentioning

confidence: 99%

Adverse Events and Patient Outcomes Among Hospitalized Children Cared for by General Pediatricians vs Hospitalists

et al. 2018

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Importance Pediatric hospital medicine is a relatively new and growing specialty. However, research remains inconclusive on outcomes for inpatients cared for by pediatric hospitalists compared with those cared for by general pediatricians. Objective To analyze outcomes, adverse events (AEs), and types of AEs associated with care provided for pediatric patients by hospitalists vs general pediatricians. Design, Setting, and Participants This cross-sectional study used data from the medical records of a US urban academic children’s hospital comprising 1423 hospitalizations between January 1, 2009, and August 31, 2015, for 57 diagnoses of patients cared for by either a hospitalist or general pediatrician. General pediatricians worked primarily in the hospital’s outpatient clinic, serving a few inpatient weeks per year, and were not the patients’ primary care physician. Data analysis was performed from July 1, 2017, to October 10, 2018. Main Outcomes and Measures Outcomes were length of stay, total costs, 30-day readmission rates, and AEs. Adverse events were documented by International Classification of Diseases, Ninth Revision, Clinical Modification codes determined by review of medical records. Adverse event categories were drug events, infections, and device-related AEs. Generalized linear models were used to analyze patient outcomes, with standard errors clustered by physician. Models were adjusted for patient characteristics, including Chronic Condition Indicators. Models were estimated with and without adjustment for physician characteristics. Results The data set contained 1423 hospitalizations among 726 female patients and 697 male patients (mean [SD] age, 6.1 [6.3] years). Hospitalists cared for 870 patients, and general pediatricians cared for 553 patients. Among the physicians, there were 57 women and 38 men; physicians were a mean (SD) 11.1 (8.1) years out of medical school. Patients cared for by general pediatricians were younger than those cared for by hospitalists (mean [SD] age, 5.4 [6.0] vs 6.5 [6.4] years; P = .001) but had similar mean (SD) Chronic Condition Indicator scores (1.5 [1.0] vs 1.5 [1.0]). A total of 33 of 56 general pediatricians (58.9%) and 24 of 39 hospitalists (61.5%) were women ( P = .006), and general pediatricians were in practice twice as long as hospitalists on average (mean [SD], 16.0 [10.3] vs 7.9 [3.8] years out of medical school; P < .001). In multivariate models adjusting for patient-level features, there were no significant differences between general pediatricians and hospitalists for mean length of stay (4.7 vs 4.6 days), total costs ($14 490 vs $15 200), and estimated 30-day readmission rate (8.9% vs 6.4%), and results were similar with adjustments for physician characteristics. Device-related AEs were higher among hospitalists (3.0%...

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“…Similar results emerged for combined stroke events exclusively (stroke and TIA HR 0.72; 95% CI 0.62-0.84) and combined cardiac events (HR 0.66; 95% CI 0.60-0.72). 18 These findings suggest support for T.…”

Section: Studies Linking Testosterone Replacement Therapy (Trt) Witmentioning

confidence: 83%

“…In a retrospective cohort study within an integrated healthcare system, the rate of composite CV events at a median follow‐up of 3.4 years for men with low T who were given TRT (n = 8808) was 16.9/1000 person‐years vs 23.9/1000 in men never given TRT (adjusted HR 0.67 for TRT group; 95% CI 0.62‐0.73). Similar results emerged for combined stroke events exclusively (stroke and TIA HR 0.72; 95% CI 0.62‐0.84) and combined cardiac events (HR 0.66; 95% CI 0.60‐0.72) . These findings suggest support for T.…”

Section: Resultsmentioning

confidence: 99%

Cardiovascular risk with androgen deprivation therapy

Rosenberg

2019

Int J Clin Pract

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Summary Background From the primary care perspective, many urologists and oncologists appear to be ignoring an FDA warning to assess patients' cardiovascular (CV) risk before instituting androgen deprivation therapy (ADT) with gonadotropin‐releasing hormone (GnRH) agonists. A growing body of data suggest an association between ADT and CV/cardiometabolic risk, particularly for GnRH agonists. Methodology The author examined available evidence regarding CV side effects with GnRH agonists and antagonists to determine what urologists, medical oncologists, primary care physicians (PCPs) and patients need to know about these risks. Results Data are inconclusive and somewhat conflicting—for example, both low testosterone and testosterone replacement have been associated with elevated CV risk. But the distinction between GnRH agonists and antagonists is becoming clearer, as agonists appear to be more strongly linked with CV risk, perhaps due to the transient testosterone surge they cause upon administration. Moreover, adverse CV events associated with GnRH agonists can emerge relatively quickly, within weeks to months. Conversely, two studies show that GnRH antagonists may significantly reduce CV risk compared to GnRH agonists. Conclusions Both GnRH agonists and antagonists carry some degree of CV risk. Although the risk appears to be lower with GnRH antagonists, urologists and oncologists should communicate with PCPs to determine patients' baseline CV risk levels before implementing ADT with either type of agent.

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Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency

Cited by 148 publications

References 39 publications

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men

Adverse Events and Patient Outcomes Among Hospitalized Children Cared for by General Pediatricians vs Hospitalists

Cardiovascular risk with androgen deprivation therapy

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