Exogenous Testosterone, Cardiovascular Events, and Cardiovascular Risk Factors in Elderly Men: A Review of Trial Data
ABSTRACT Increasing interest in the use of supplemental testosterone has led to a heightened focus on the safety of testosterone in elderly males, with a particular emphasis on cardiovascular risk.
To evaluate, based on available clinical trial data, whether exogenous testosterone administration in middle-aged to elderly men increases cardiovascular risk, and to assess whether these effects differ in hypogonadal vs. eugonadal subjects.
MEDLINE search from 2004 to present of all meta-analyses and randomized, controlled clinical trials of testosterone administration in male subjects ≥ 45 years old that included measurements of cardiovascular outcomes or known cardiovascular risk factors before and after treatment with testosterone.
The effects of testosterone treatment on cardiovascular events and cardiovascular risk factors were assessed.
In clinical trials where testosterone has been used in patients with preexisting cardiovascular conditions, the effect on disease symptoms has typically been either neutral or beneficial. Based on clinical trial data, testosterone treatment has minimal effect on cardiovascular risk factors with the exception of an increase in hematocrit, which is consistently seen with testosterone treatment, and a decrease in high-density lipoprotein cholesterol, which is an inconsistent response. Responses of hypogonadal and eugonadal men to testosterone treatment in terms of cardiovascular risk are generally similar. Testosterone treatment has not been reported to increase the incidence of cardiovascular events with the possible exception of one trial in frail elderly men.
Available clinical trial data indicate that the use of testosterone in middle-aged to elderly men does not increase cardiovascular risk nor does it unfavorably modify cardiovascular risk profile. Prospective data from large, well-designed, long-term trials of testosterone treatment are lacking and will be required to verify the cardiovascular efficacy/safety of chronic treatment.
- SourceAvailable from: Marcello Maggio[Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVE: The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. METHODS: Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. RESULTS: The mean age (±SD) of the 419 men and 502 women was 75.0 ± 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01). CONCLUSIONS: Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively.Atherosclerosis 10/2012; 225(2). DOI:10.1016/j.atherosclerosis.2012.09.014 · 3.97 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Obesity negatively affects human health. Limiting food intake, while producing some weight loss, results in reduction of lean body mass. Combined with moderate exercise it produces significant weight loss, maintains lean body mass and improves insulin sensitivity, but appears difficult to adhere to. Bariatric surgery is clinically effective for severely obese individuals compared with non-surgical interventions, but has limitations. Clinical and pre-clinical studies have implicated a role for testosterone (T) in the patho-physiology of obesity. Evidence Acquisition and Synthesis: A literature search in PubMed on the role of T in counteracting obesity and its complications. Obesity per se impairs testicular T biosynthesis. Furthermore, lower-than-normal T levels increase accumulation of fat depots, particularly abdominal (visceral) fat. This fat distribution is associated with development of metabolic syndrome (MetS) and its sequels, namely type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). T treatment reverses fat accumulation with significant improvement in lean body mass, insulin sensitivity and biochemical profiles of cardiovascular risk. The contribution of T to combating obesity in hypogonadal men remains largely unknown to medical professionals managing patients with obesity and metabolic syndrome. Many physicians associate T treatment in men with risks for prostate malignancy and CVD. These beliefs are not supported by recent insights. While overall treatment of obesity is unsuccessful, T treatment of hypogonadal men may be effective, also because it improves mood, energy, reduces fatigue and may motivate men to adhere to diet and exercise regimens designed to combat obesity.Current diabetes reviews 01/2012; 8(2):131-43. DOI:10.2174/157339912799424573
- [Show abstract] [Hide abstract]
ABSTRACT: Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years) men. To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs <65 years old. Data for participants 65-74 vs ≥75 years old were also compared. Data were from TRiUS (Testim Registry in the United States), which enrolled 849 hypogonadal men treated with Testim(®) 1% (50-100 mg testosterone gel/day) for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT), free testosterone (FT), and prostate-specific antigen (PSA) levels. Comparisons of parameters were made using Fisher's exact test or analysis of variance. Nonparametric Spearman's ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters. Of the registry participants at baseline with available age information, 16% (133/845) were ≥65 years old. They were similar to men <65 years old in the duration of hypogonad-ism prior to enrollment (∼1 year), TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng/mL for ≥65 vs 1.14 ± 0.84 ng/mL for <65 years old, P = 0.1). Baseline values for the >75-year-old subcohort were not significantly different from subcohorts aged 65-74 years and <65 years. Hypogonadal men ≥65 years old showed significant benefit from TRT over 12 months, similar to that found for hypogonadal men <65 years old. TRT was well tolerated in older patients, successfully increased testosterone level regardless of age, and did not significantly increase PSA levels in older men.Clinical Interventions in Aging 08/2012; 7:321-30. DOI:10.2147/CIA.S32036 · 1.82 Impact Factor