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TRT risks may be overstated
by Wayne Kuznar
NEW ORLEANS -- Testosterone replacement therapy (TRT) in older men with hypogonadism may be safe and even improve cardiovascular risk.
"In the correctly selected patients, testosterone can be beneficial, especially when combined with lifestyle modification," said Tobias Köhler, MD, MPH, of Southern Illinois University, Carbondale. "It seems to be safe with the meta-analyses and the recent data from a cardiac and prostate cancer perspective. However, we still have to do more due diligence to say that it's absolutely safe."
Köhler moderated a press conference at the American Urological Association annual meeting where the data were reported.
TRT was not associated with an increased risk of thrombotic events in this population in one study, and in two others, was associated with an improvement in metabolic factors.
In men older than 65 years with confirmed hypogonadism, defined as serum testosterone <300 ng/mL, there was no statistically significant difference in the prevalence of myocardial infarction, transient ischemic attack/cerebrovascular accident or pulmonary embolism over 3 years between men treated with TRT and those not treated, reported Ranjith Ramasamy, MD, Baylor College of Medicine, Houston.
The U.S. Food and Drug Administration required changes to the label of testosterone products, noting a "possible increased cardiovascular risk associated with testosterone use," prompting an evaluation of thrombotic risk in men older than 65 years with symptomatic hypogonadism who were treated with TRT.
In a retrospective char t review, the rates of thrombotic events were compared between 153 men treated with TRT and 64 age- and comorbidity-matched men who were naïve to TRT. Men on TRT were receiving injections (n=53), gel (n=47) or pellets (n=53). The treatment group had at least one follow-up after TRT; the control group had at least two testosterone levels drawn after age 65.
The rate of thrombotic events was 2.5% in the group receiving TRT and 1.5% in the men not on TRT, a nonsignificant difference (P=0.8). Although the study was small, the study had adequate power to detect a significant difference in the rate of cardiovascular events, said Ramasamy. No man who received TST died, whereas five hypogonadal men who did not receive TST died (P=0.007).
"Testosterone supplementation appears to be a safe and effective therapy for symptomatic hypogonadism in elderly men," he concluded.
In a prospective observational study, long-term treatment with testosterone injections improved metabolic control in hypogonadal men with type 2 diabetes. Ahmad Haider, MD, a urologist in Bremerhaven, Germany, described a registry study of 340 men (mean age, 60 years) with serum testosterone ≤350 ng/mL who received testosterone injections for up to 87 months at a single urology office. The data he presented were from a subgroup analysis of 120 men with type 2 diabetes, 89% of whom were obese. All men had their diabetes managed by their family physicians.
Trough testosterone levels rose form 10.0 nmol/L at baseline to 15 to 18 nmol/L over the course of TRT.
Body weight decreased progressively, to a final level that was 21.36 kg lower than baseline (P<0.0001). Obese men lost 18.25% of their body weight, overweight men lost 13.64% and normal weight men gained 2.82%. Waist circumference declined by 11.34 cm (P<0.0001). Changes in metabolic parameters were as follows:
Fasting glucose fell by 22.57 mg/dL (P<0.0001)
Hemoglobin A1c declined by 2.28% (P<0.0001)
The total cholesterol (TC):high-density lipoprotein (HDL) cholesterol ratio fell from 4.9 to 2.52 (P<0.0001)
The triglyceride:HDL ratio declined from 4.84 to 2.49 (P<0.0001)
Systolic blood pressure (SBP) decreased from 160.48 to 137.47 mm Hg (P<0.0001)
Diastolic blood pressure (DBP) decreased from 96.03 to 77.17 mm Hg (P<0.0001)
"Erectile function on a 30-point scale (International Index of Erectile Function [IIEF-EF]) improved significantly, despite the fact that patients were aging," said Haider. "No patient dropped out; medication adherence was excellent, and there were no major cardiovascular events during the observation period."
A third study lends further support that long-term TRT -- up to 11 years -- results in sustained anthropometric, endocrine, urologic and metabolic parameters, said Aksam Yassin, MD.
In a prospective registry, outcomes were tracked among 262 hypogonadal men (mean age: 59. 5 years) who received testosterone undecanoate injections in 12-week intervals for a maximum of 11 years. Excluded from the analysis were 147 men in whom TRT was interrupted because of reimbursement issues and seven in whom prostate cancer was diagnosed, leaving 115 for the analysis.
Compared with baseline, weight dropped by 18.39 kg, waist circumference declined by 12.97 cm and body mass index declined by 5.88 kg/m2 (all P<0.0001) by year 11.
Lipid parameters also improved: from baseline, TC fell by 94.97 mg/dL, HDL cholesterol increased by 15.23 mg/dL and low-density lipoprotein cholesterol dropped by 66.91 mg/dL to year 11 (all P<0.0001).
Fasting glucose decreased by 35.48 mg/dL, with most of the reduction occurring in the first year of treatment. HbA1c declined by 1.67% in the subgroup of patients with type 2 diabetes (both P<0.0001).
SBP decreased by 19.24 mm Hg and DBP by 10.23 mm Hg over the 11 years (both P<0.0001).
The International Prostate Symptom Score improved by 5.44 points and the IIEF-EF improved by 8.7 points (P<0.0001 for both).
Although the results were impressive, "the danger here is to attribute all of these [metabolic] improvements to testosterone," said Köhler. "You had a group of men that lost 40 pounds; the testosterone likely had a role in weight reduction. If you lose 20 kg, all of these things are going to happen."
Bayer Pharma AG partially funded data entry and statistical analyses for Haider and colleagues.
The remaining authors reported no disclosures.
TRT risks may be overstated
by Wayne Kuznar
NEW ORLEANS -- Testosterone replacement therapy (TRT) in older men with hypogonadism may be safe and even improve cardiovascular risk.
"In the correctly selected patients, testosterone can be beneficial, especially when combined with lifestyle modification," said Tobias Köhler, MD, MPH, of Southern Illinois University, Carbondale. "It seems to be safe with the meta-analyses and the recent data from a cardiac and prostate cancer perspective. However, we still have to do more due diligence to say that it's absolutely safe."
Köhler moderated a press conference at the American Urological Association annual meeting where the data were reported.
TRT was not associated with an increased risk of thrombotic events in this population in one study, and in two others, was associated with an improvement in metabolic factors.
In men older than 65 years with confirmed hypogonadism, defined as serum testosterone <300 ng/mL, there was no statistically significant difference in the prevalence of myocardial infarction, transient ischemic attack/cerebrovascular accident or pulmonary embolism over 3 years between men treated with TRT and those not treated, reported Ranjith Ramasamy, MD, Baylor College of Medicine, Houston.
The U.S. Food and Drug Administration required changes to the label of testosterone products, noting a "possible increased cardiovascular risk associated with testosterone use," prompting an evaluation of thrombotic risk in men older than 65 years with symptomatic hypogonadism who were treated with TRT.
In a retrospective char t review, the rates of thrombotic events were compared between 153 men treated with TRT and 64 age- and comorbidity-matched men who were naïve to TRT. Men on TRT were receiving injections (n=53), gel (n=47) or pellets (n=53). The treatment group had at least one follow-up after TRT; the control group had at least two testosterone levels drawn after age 65.
The rate of thrombotic events was 2.5% in the group receiving TRT and 1.5% in the men not on TRT, a nonsignificant difference (P=0.8). Although the study was small, the study had adequate power to detect a significant difference in the rate of cardiovascular events, said Ramasamy. No man who received TST died, whereas five hypogonadal men who did not receive TST died (P=0.007).
"Testosterone supplementation appears to be a safe and effective therapy for symptomatic hypogonadism in elderly men," he concluded.
In a prospective observational study, long-term treatment with testosterone injections improved metabolic control in hypogonadal men with type 2 diabetes. Ahmad Haider, MD, a urologist in Bremerhaven, Germany, described a registry study of 340 men (mean age, 60 years) with serum testosterone ≤350 ng/mL who received testosterone injections for up to 87 months at a single urology office. The data he presented were from a subgroup analysis of 120 men with type 2 diabetes, 89% of whom were obese. All men had their diabetes managed by their family physicians.
Trough testosterone levels rose form 10.0 nmol/L at baseline to 15 to 18 nmol/L over the course of TRT.
Body weight decreased progressively, to a final level that was 21.36 kg lower than baseline (P<0.0001). Obese men lost 18.25% of their body weight, overweight men lost 13.64% and normal weight men gained 2.82%. Waist circumference declined by 11.34 cm (P<0.0001). Changes in metabolic parameters were as follows:
Fasting glucose fell by 22.57 mg/dL (P<0.0001)
Hemoglobin A1c declined by 2.28% (P<0.0001)
The total cholesterol (TC):high-density lipoprotein (HDL) cholesterol ratio fell from 4.9 to 2.52 (P<0.0001)
The triglyceride:HDL ratio declined from 4.84 to 2.49 (P<0.0001)
Systolic blood pressure (SBP) decreased from 160.48 to 137.47 mm Hg (P<0.0001)
Diastolic blood pressure (DBP) decreased from 96.03 to 77.17 mm Hg (P<0.0001)
"Erectile function on a 30-point scale (International Index of Erectile Function [IIEF-EF]) improved significantly, despite the fact that patients were aging," said Haider. "No patient dropped out; medication adherence was excellent, and there were no major cardiovascular events during the observation period."
A third study lends further support that long-term TRT -- up to 11 years -- results in sustained anthropometric, endocrine, urologic and metabolic parameters, said Aksam Yassin, MD.
In a prospective registry, outcomes were tracked among 262 hypogonadal men (mean age: 59. 5 years) who received testosterone undecanoate injections in 12-week intervals for a maximum of 11 years. Excluded from the analysis were 147 men in whom TRT was interrupted because of reimbursement issues and seven in whom prostate cancer was diagnosed, leaving 115 for the analysis.
Compared with baseline, weight dropped by 18.39 kg, waist circumference declined by 12.97 cm and body mass index declined by 5.88 kg/m2 (all P<0.0001) by year 11.
Lipid parameters also improved: from baseline, TC fell by 94.97 mg/dL, HDL cholesterol increased by 15.23 mg/dL and low-density lipoprotein cholesterol dropped by 66.91 mg/dL to year 11 (all P<0.0001).
Fasting glucose decreased by 35.48 mg/dL, with most of the reduction occurring in the first year of treatment. HbA1c declined by 1.67% in the subgroup of patients with type 2 diabetes (both P<0.0001).
SBP decreased by 19.24 mm Hg and DBP by 10.23 mm Hg over the 11 years (both P<0.0001).
The International Prostate Symptom Score improved by 5.44 points and the IIEF-EF improved by 8.7 points (P<0.0001 for both).
Although the results were impressive, "the danger here is to attribute all of these [metabolic] improvements to testosterone," said Köhler. "You had a group of men that lost 40 pounds; the testosterone likely had a role in weight reduction. If you lose 20 kg, all of these things are going to happen."
Bayer Pharma AG partially funded data entry and statistical analyses for Haider and colleagues.
The remaining authors reported no disclosures.
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