BioAge Health Newsletter
Thanksgiving 2020
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Newletter Highlight
Testosterone Replacement
Decreases Mortality Risk in Men
read article below
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Testosterone Replacement
Decreases Mortality Risk in Men
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Main points:
-Low testosterone is associated with an increased mortality rate
-Treating testosterone deficiency to a normal testosterone level reduces mortality rate
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Glossary:
-Mortality rate: number of deaths over a given period of time.
-All-cause mortality: death from all causes
-Endogenous testosterone: testosterone that is naturally produced
-Meta-analysis: A study that combines the results of multiple studies. The data are pooled together to provide a greater statistical power than any of the individual, smaller studies
-Observational study: A group of individuals who are observed to measure certain risk factors or outcomes. It’s designed to measure the degree of effect but cannot confirm cause and effect relationship
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There is no larger umbrella that encompasses the benefits of replacing low testosterone in men, than the finding that testosterone replacement decreases the risk of all-cause mortality in men who suffer from low testosterone. This finding likely rests on the associations of testosterone deficiency and increased risk of diabetes, obesity, lipid abnormalities, heart disease and osteoporosis, as well as its anti-inflammatory and anticoagulant properties. Heart disease is the leading cause of death in men, and the association of low testosterone and increased heart disease has also been an area of significant study.
This finding of reduced of all-cause mortality is represented in three studies that I’ll review here. I selected these articles to show the volume of studies done on this issue, and the progression in the understanding of the association between low testosterone and increased death, and eventually the confirmation of benefit in mortality with adequate treatment. You can use the links to view the summaries (abstracts); articles that are open access can be read in their entirety.
Araujo et al. in their article published in 2011 initially identified 820 studies (from 1966 to 2010) that looked at low endogenous testosterone and mortality. These studies were eventually whittled down to 12 studies that were amenable to a meta-analysis. The combined 12 studies included a total of over 16,000 men with an average age of 61 years, and average testosterone level of 487 ng/dl; the average length of the studies was 9.7 years. The study showed low testosterone levels were associated with increased risk of all-cause (as well as cardiovascular) mortality. A decrease in testosterone of two standard deviations was associated with a 35% increased risk of all-cause mortality (and 25% increased risk of death due to heart disease). The authors however conservatively recommended caution in the interpretation of their meta-analysis, because the differences in characteristics of the different studies could theoretically weaken confidence in the overall conclusion.
In 2012, Shores et al. looked at 1031 male veterans ages 40 and older with low testosterone (</=250 ng/dl). Their study compared men in that group who were treated with testosterone replacement, with those who did not receive treatment; the average time of evaluation was 15 months. The percent mortality in testosterone-treated men was 10.3% compared to 20.7% in
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untreated men. Overall, they found a 39% decreased mortality risk in the treated, with a greater reduction of mortality risk in younger men (age <60) in the study. Additionally, they found that lower baseline testosterone levels and shorter duration of treatment were both associated with higher mortality rates.
In 2015, Sharma et al. examined the records of over 83,000 male veterans ages 50 or older with documented low testosterone. The men were evaluated for an average period of 4 ½ to 6 years. They divided the men into three groups: one that was treated with testosterone to normal testosterone levels (Group 1), a second group that was treated with testosterone, but not to normal levels (Group 2), and a third group that were not treated and remained with low levels (Group 3).
The study showed that the men in Group 1 (adequately treated) were 56% less likely to die during the follow-up period compared to the Group 3 (untreated) men. Additionally, they were also 24% less likely to suffer a heart attack, and 36% less likely to have a stroke.
The differences between Group 1 and Group 2 (sub-therapeutically treated) were similar to the differences between Group 1 and 3, and data between Groups 2 and 3 were similar to each other.
From the study: "It is the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the total testosterone levels. Patients who failed to achieve the therapeutic range after testosterone replacement therapy did not see a reduction in [heart attack] or stroke and had significantly less benefit on mortality." This large and lengthy study was also important because other studies that raised controversy about testosterone replacement therapy, suggesting increased risk with testosterone treatment, but did not confirm that the subjects were actually treated to a normal testosterone level, and therefore it’s difficult to confirm whether adverse effects were due to treatment or inadequate treatment.
This issue of increased mortality is an important overlying justification of testosterone treatment for men with low testosterone. It’s just the start of reviewing the importance of treating low testosterone in men; other studies have associated low testosterone with obesity, type 2 diabetes, heart disease, and inflammatory disease. Please continue to follow the newsletters for this ongoing discussion, and feel free to share with me your thoughts about this review.
CLK MD
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