Testosterone Supplementation In Older Men Research Articles

Sex Hormone and Colorectal Cancer: The Knowns and Unknowns.

Sex hormones have been suggested as a contributor to gender disparity in incidence and mortality of colorectal cancer, but previous observational studies on endogenous sex hormones and colorectal cancer risk have led to contradictory results. Leveraging the large-scale UK biobank resource, Dimou and colleagues performed both observational and Mendelian randomization (MR) analyses to investigate the association of serum testosterone and sex hormone binding globulin concentrations with the risk of colorectal cancer. Although the findings provide little evidence for independent roles of the hormones in colorectal cancer, further interrogation of possible mediating effects of sex hormones on the causal pathways of colorectal cancer could deepen our understanding of colorectal cancer etiology and improve tailored prevention. While MR analysis is useful for inferring causality in observational studies, the current null results should be interpreted with caution because of insufficient statistical power and predefined assumptions of linearity. Moreover, given the widespread use of testosterone supplementation in older men to restore age-related decline of endogenous concentrations, large and long-term randomized controlled trials are required to clarify the effect of testosterone on colorectal cancer risk, which would provide critical evidence for health decision making.See related article by Dimou et al., p. 1336.

Re: Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity.

Re: Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity.

Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity.

Testosterone increases skeletal muscle mass and strength, but long-term effects of testosterone supplementation on aerobic capacity, or peak oxygen uptake (V̇O2peak), in healthy older men with low testosterone have not been evaluated. To determine the effects of testosterone supplementation on V̇O2peak during incremental cycle ergometry. A double-blind, randomized, placebo-controlled, parallel-group trial (Testosterone's Effects on Atherosclerosis Progression in Aging Men). Exercise physiology laboratory. Healthy men aged ≥ 60 years with total testosterone levels of 100 to 400 ng/dL (3.5 to 13.9 nmol/L) or free testosterone levels < 50 pg/mL (174 pmol/L). Randomization to 1% transdermal testosterone gel adjusted to achieve serum levels of 500 to 950 ng/dL or placebo applied daily for 3 years. Change in V̇O2peak. Mean (±SD) baseline V̇O2peak was 24.2 ± 5.2 and 23.6 ± 5.6 mL/kg/min for testosterone and placebo, respectively. V̇O2peak did not change in men treated with testosterone but fell significantly in men receiving placebo (average 3-year decrease, 0.88 mL/kg/min; 95% CI, -1.39 to 0.38 mL/kg/min; P = 0.035); the difference in change in V̇O2peak between groups was significant (average 3-year difference, 0.91 mL/kg/min; 95% CI, 0.010 to 0.122 mL/kg/min; P = 0.008). The 1-g/dL mean increase in hemoglobin (P < 0.001) was significantly associated with changes in V̇O2peak in testosterone-treated men. The mean 3-year change in V̇O2peak was significantly smaller in men treated with testosterone than in men receiving placebo and was associated with increases in hemoglobin. The difference in V̇O2peak change between groups may indicate attenuation of its expected age-related decline; the clinical meaningfulness of the modest treatment effect remains to be determined.

More Data on Testosterone Supplementation in Older Men

In a recently published, industry-funded, randomized trial that involved about 300 men (mean age, 68; morning total testosterone range, 100–400 ng/dL),

Testosterone Supplementation in Older Men with Low Testosterone Levels

As men age, their blood testosterone levels generally decline, often to levels in the low or low-normal ranges specified by commercial laboratories. Testosterone supplementation is being prescribed increasingly for such men, some of whom report “aging-male symptoms.” Although testosterone supplementation undoubtedly improves aging-male symptoms and sexual function in men who have overt primary or secondary hypogonadism, the value of supplementation in other men has not been established. A multi-institutional team conducted a randomized …

Testosterone and cardiovascular disease risk

Ageing is accompanied by a reduction in circulating testosterone and progressive accumulation of medical morbidities. There is an intense debate whether low testosterone contributes to ill-health as opposed to being a biomarker for its presence. Prescriptions for testosterone are rising on a background of concern over potential adverse effects. This review examines evidence relating androgens to cardiovascular risk in older men. Observational studies show lower risk of cardiovascular events in older men with higher testosterone, and lower mortality from ischaemic heart disease in men with higher concentrations of its more potent androgenic metabolite dihydrotestosterone. However, randomized controlled trials of testosterone supplementation have been underpowered for the outcome of cardiovascular events. Recent meta-analyses have reached contrasting conclusions regarding cardiovascular adverse events associated with testosterone therapy. Retrospective studies of prescription databases have produced controversial and conflicting results. Additional randomized controlled trials are required to clarify the role of testosterone supplementation in older men in the absence of pituitary or gonadal disease. Pending such studies, testosterone therapy should be considered in androgen-deficient men, with evaluation of potential benefits and risks.

Testosterone and ill-health in aging men

As men age, testosterone levels decline, and decreased testosterone levels are associated with increased risks of osteoporosis, metabolic syndrome, type 2 diabetes mellitus and mortality. Nevertheless, it is still uncertain whether reduced testosterone level is a cause of ill-health or a marker of pre-existing disease, as systemic illness lowers testosterone levels. Most circulating testosterone is bound to sex-hormone-binding globulin (SHBG) and albumin, whereas a small proportion circulates as free testosterone. Decreased SHBG level is associated with increased risks for insulin resistance and metabolic syndrome, although it would also be expected to be associated with increased free testosterone level. During male aging, total and free testosterone levels fall while SHBG level rises. Thus, associations between decreasing androgens and negative health outcomes might differ across men of various ages. Trials of testosterone therapy report benefits for body composition and BMD, but there are limited data on the effect of testosterone supplementation on cardiovascular risk. Whereas men who have androgen deficiency should be considered for testosterone therapy, the role of testosterone supplementation in older men who are not clearly hypogonadal requires further clarification. Further studies are also needed to establish whether the age-related decline in circulating testosterone level in men can be modified or prevented.

Testosterone Supplementation in Older Men

The progressive decline in testosterone levels as men age has led to suggestions that physical, functional, or cognitive benefits could accrue from testosterone supplementation later in life. In a double-blind Dutch study, 237 healthy men (mean age, 67) with low-normal circulating testosterone levels (mean baseline total testosterone level, 308 ng/dL) were randomly assigned to …

Testosterone and Cognition in Normal Aging and Alzheimers Disease: An Update

There is evidence to suggest that testosterone loss constitutes a risk for cognitive decline and possibly dementia, and that elderly men might benefit from exogenous supplementation of testosterone. Studies in non-human animals repeatedly report neuroexcitatory and neuroprotective properties of testosterone and enhanced memory performance after acute or chronic treatment. Positive effects of testosterone supplementation in older men have been reported in several, but not all, studies and require replication in larger randomized clinical trials before recommendations for clinical practice can be made. The current review summarizes recent studies on the neurobiological connection between testosterone and cognitive function in humans and non-human animals. When appropriate, we use the hippocampus as a model structure given it's involvement in sexually dymorphic spatial ability and sensitivity to both androgens and aging. In addition, a number of potential explanations of the discrepancy between data obtained in humans and non-human animals are discussed.

Testosterone Levels, LH Levels, and Erectile Dysfunction

Given recent controversies about testosterone supplementation in older men (Journal Watch Dec 28 2006), pinning down relationships between testosterone

Effect of high-dose estrogen on memory in men with prostate cancer

4650 Background: Estrogen replacement in women, and in female animal models, improves memory and changes the structure and physiology of relevant brain regions. Estrogen replacement in women improves long term verbal memory (hippocampal function) but may not affect short term working memory (prefrontal cortex function). Gonadectomy in male rats decreases synapse density in the hippocampus, a region important for long term memory. Testosterone, but not estrogen, replacement restores hippocampal synapse spine density. Testosterone supplementation in older men produces improvements in short term working memory. Little is known about the neural and cognitive effects of androgen suppression or estrogen therapy in men with prostate cancer. Methods: We compared the long term verbal memory (using the immediate and delayed Paragraph Recall test), and working memory (using Subject Ordered and Trails tests) of androgen-deprived men with androgen-independent prostate cancer before and 1 month after starting second-line hormonal therapy with transdermal estradiol 45.6 mg (six 7.6 mg patches) applied every 7 days. Results: Androgen deprived men treated with estradiol had a significant improvement in their paragraph recall performance but no change in working memory. Conclusions: High dose estradiol may have had beneficial but specific effects on cognitive performance. The mechanism of this effect is not clear. Previous studies have shown beneficial effects of testosterone on the brain and performance in androgen deprived male rats, but effects of estradiol have only been found for recovery of function after brain injury. Thus, the beneficial effects of estradiol in this study may be due to its use in combination with androgen suppression, disease and/or an aging brain. Further studies using additional cognitive measures and control subjects will further elucidate the brain and cognitive effects of estradiol in prostate cancer patients. No significant financial relationships to disclose.

Testosterone Supplementation for Aging-Associated Sarcopenia

Aging of humans is associated with a loss of muscle mass and function, and an increase in fat mass. Epidemiologic studies have demonstrated a correlation between bioavailable testosterone concentrations and fat-free mass and muscle strength. Testosterone replacement in older men with low testosterone levels increases fat-free mass and muscle strength, and decreases fat mass. However, we do not know whether testosterone replacement improves physical function and other health-related outcomes, or reduces the risk of disability, falls, or fractures in older men with low testosterone levels. The long-term risks and benefits of testosterone supplementation in older men are not known.

Testosterone supplementation in older men: a rational idea whose time has not yet come.

Forty years after the introduction of estrogens, the debate over the risks and benefits of estrogen replacement therapy in postmenopausal women is still not entirely settled. In contrast, the issues of testosterone replacement in older men are just beginning to be addressed. There is agreement that total, free, and bioavailable testosterone (ie, not bound by sex hormone-binding globulin) levels decline progressively with advancing age (Harman and Tsitouras, 1980, 1982; Murono et al, 1982; Nieschlag et al, 1982; Zumoff et al, 1982; Bremner and Prinz, 1983; Davidson et al, 1983; Nankin and Calkins, 1986; Tenover et al, 1987; Gray et al, 1991; Vermeulen, 1991; Simon et al, 1992; Rudman and Shetty, 1994; Morley et al, 1997; Zmuda et al, 1997; Harmon et al, in press), and that many of the physiological changes that occur with advancing age such as loss of bone and muscle mass; increased fat mass; impairment of physical, sexual, and cognitive functions; loss of body hair; and decreased hemoglobin levels, are similar to those associated with androgen deficiency in young men. However, the beneficial effects of testosterone replacement on health-related outcomes in older men with low testosterone levels have yet to be demonstrated, and the risks of long-term testosterone administration, particularly the risks of prostate cancer and heart disease, remain unknown. Therefore, it is premature to make a general recommendation about testosterone supplementation in older men. Despite the paucity of efficacy and safety data, the sales of testosterone and other androgenic products have witnessed explosive growth recently

VIII. Conclusion--Research Design Issues in Examining the Effects of Testosterone Supplementation in Older Men

VIII. Conclusion--Research Design Issues in Examining the Effects of Testosterone Supplementation in Older Men

VIII. Conclusion—Research Design Issues in Examining the Effects of Testosterone Supplementation in Older Men

VIII. Conclusion—Research Design Issues in Examining the Effects of Testosterone Supplementation in Older Men