Cardiovascular Issues in Hypogonadism and Testosterone Therapy

Shabsigh, Ridwan; Katz, Mark H.; Yan, Grace W.; Makhsida, Nawras

doi:10.1016/j.amjcard.2005.10.009

Cited by 79 publications

(55 citation statements)

References 35 publications

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“…Male hypogonadism is associated with insulin resistance, increased production of pro-inflammatory cytokines, elevated fibrinogen and an atherogenic lipid profile (11). Conversely, testosterone replacement increases antioxidant levels, and improves the cytokine profile, insulin sensitivity and abdominal obesity (12)(13)(14). These observations suggest a more complex role for testosterone and are consistent with the hypothesis that androgen deficiency plays a role in the pathogenesis of IHD.…”

Section: Introductionsupporting

confidence: 77%

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

Hyde

Norman

Flicker

et al. 2011

European Journal of Endocrinology

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Context: Hypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events. Objective: To determine whether testosterone and its associated hormones, sex hormone-binding globulin (SHBG) and LH, predict IHD events in older men. Design: Prospective cohort study. Methods: Between 2001 and 2004, 3637 community-dwelling men aged 70-88 years underwent a clinical assessment of cardiovascular risk factors and biochemical assessment of testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Participants were followed until December 2008 using electronic record linkage to capture IHD events (hospital admission or death). Results: Mean follow-up was 5.1 years. During this period, 618 men (17.0%; 95% confidence interval (CI) 15.8, 18.3%) experienced an event, of which 160 were fatal. Men with higher baseline total or free testosterone levels experienced fewer IHD events (hazard ratio (HR)Z0.89; 95% CI 0.82, 0.97 and HRZ0.86; 95% CI 0.79, 0.94 for each one S.D. increase in total and free testosterone respectively). These associations were maintained after adjustment for age and waist:hip ratio but did not persist after adjustment for prevalent IHD or other cardiovascular risk factors. SHBG was not associated with IHD events. In contrast, higher LH levels were associated with reduced event-free survival in both univariate (HRZ1.15; 95% CI 1.08, 1.22) and adjusted analyses (HRZ1.08; 95% CI 1.01, 1.15). Conclusions: Dysregulation of the hypothalamic-pituitary-gonadal axis may be a risk factor for IHD. Further studies of men with either elevated LH or low testosterone are warranted.

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Section: Introductionsupporting

confidence: 77%

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

Hyde

Norman

Flicker

et al. 2011

European Journal of Endocrinology

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“…Also, it has been shown that low endogenous testosterone levels are associated with increased risk for both all-cause and cardiovascular mortality (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Evidence from short-term studies indicated that testosterone replacement therapy may improve some specific cardiovascular risk factors, such as visceral obesity, insulin resistance, lipid and inflammatory profiles, and exercise-induced cardiac ischemia (13).…”

mentioning

confidence: 99%

Endogenous Testosterone and Mortality in Male Hemodialysis Patients

Güngör

Kırçelli

Carrero

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey.Design, settings, participants, & measurements: A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile.Results: Mean testosterone level was 8.69 ؎ 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P ‫؍‬ 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P ‫؍‬ 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses.Conclusions: Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

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“…Over the last decade several papers have examined the relationship of androgens with cardiovascular disease and concluded that it is no longer tenable to regard testosterone as a culprit in the etiology of cardiovascular disease [159][160][161][162][163]. Recent epidemiological studies have found that low testosterone levels are a predictor of mortality in elderly men [164][165][166][167][168].…”

Section: Cardiovascular Diseasementioning

confidence: 99%

Androgens and male aging: current evidence of safety and efficacy

Gooren¹

2010

Asian J Androl

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Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.

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Cardiovascular Issues in Hypogonadism and Testosterone Therapy

Cited by 79 publications

References 35 publications

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

Endogenous Testosterone and Mortality in Male Hemodialysis Patients

Androgens and male aging: current evidence of safety and efficacy

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