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Health Protocols

Male Hormone Restoration

Effects of Age-Related Decline in Testosterone Levels and Testosterone Therapy

The exact cause of the age-related reduction in testosterone levels is not known; it is probably the result of a combination of factors, including:

  • Increasing body fat (especially belly fat, and therefore increasing aromatase activity)
  • Oxidative damage to tissues responsible for the production of testosterone
  • Reduction in testicular testosterone synthesis
  • Declining levels of precursor molecules, such as DHEA
  • Nutritional status and liver function

The consequences of declining testosterone levels are striking

Body Composition and Inflammation

Testosterone affects fat cell metabolism and fat loss in several ways: inhibiting fat storage by blocking a key enzyme called lipoprotein lipase that is necessary for the uptake of fat into the body’s fat cells; stimulating fat burning by increasing the number of specific receptors on the fat-cell membrane that release stored fat; increasing insulin sensitivity; enhancing growth of muscle fibers; and decreasing fat deposits. All of these effects promote lean body mass and reduce fat mass.16,17 Placebo-controlled trials have demonstrated both significant increases in lean body mass and decreases in fat mass after varying courses of testosterone treatment in older men. In these studies, the greatest favorable changes in body composition were seen in participants with low baseline testosterone levels who received testosterone therapy for 12 months or longer.18

Emergent evidence suggests that maintaining youthful testosterone levels may help aging men avert a variety of inflammation-mediated disease, such as atherosclerosis and arthritis. By powerfully suppressing the activity an enzyme called 5-lipoxygenase, testosterone calms a fundamental pro-inflammatory pathway involved in the synthesis of signaling molecules known as leukotrienes.19 Leukotrienes are derivatives of the pro-inflammatory omega-6 fatty acid arachidonic acid; these molecules underlie much of the inflammatory development of asthma and bronchitis, and play a role in the pathology of cardiovascular disease and diabetes as well.20,21

In a study involving 184 men with low testosterone levels, 18 weeks of testosterone replacement therapy suppressed markers of inflammation including IL-1β, TNF-α, and C-reactive protein. Moreover, when compared to men who received a placebo control, men receiving testosterone replacement exhibited significant decreases in body weight, and body mass index (BMI), and waist circumference.22 The reduction in waist circumference indicates that testosterone reduces fat accumulation around the trunk of the body; this is particularly important since central fat mass and is strongly associated with increased susceptibility to inflammatory diseases and mortality.23

Musculoskeletal System

Bone integrity rests upon a balance between bone formation and bone resorption, which is controlled by multiple factors—including levels of estrogen and testosterone.24,25 In a clinical trial, testosterone increased bone mineral density in elderly men.26 Testosterone supplementation also has a positive effect on muscle metabolism and strength.27 This positive effect is undiminished with age.

Central Nervous System (CNS)

Key to aging well is an optimistic outlook on life and the ability to engage in social and physical activity. However, low levels of testosterone have been associated with depression and other psychological disorders.28 To make matters worse for aging men, many conventional antidepressant medications suppress libido. Some experts suggest that testosterone therapy might reduce the need for the antidepressant medications entirely.29,30 Furthermore, testosterone treatment often increases feelings of well-being.31

Cognition and alertness are also governed, in part, by testosterone’s effects on the CNS.32 Low testosterone levels have been shown to correlate with lower scores on various psychometric tests,33 and similar effects have been reported in men undergoing androgen (male hormone)-deprivation therapy for prostate cancer.34

Testosterone also acts as an endogenous neuroprotective agent, able to support neuron integrity against a variety of toxic insults, including oxidative stress.35,36 In addition, testosterone has been shown to reduce β-amyloid accumulation, an important pathophysiologic factor in Alzheimer’s disease.37,38

Testosterone improves neuron survival in brain regions vulnerable to neurodegenerative disease. This may explain the association of low testosterone levels in men with neurodegenerative diseases.39,40 Studies demonstrate testosterone loss occurred 5‒10 years prior to Alzheimer’s disease diagnosis. This suggests low testosterone is an important risk factor for Alzheimer’s disease.41,42 In a clinical study of 36 men recently diagnosed with Alzheimer’s disease, intramuscular testosterone treatment with 200 mg every two weeks for up to one year was associated with improvement in both overall cognitive ability as well as critical visual-spatial function.43

Glucose and Lipid Metabolism

Testosterone also has been linked to metabolic function in the body. Specifically, studies have found inverse associations between the severity of metabolic syndrome, a condition characterized by excess abdominal fat, high cholesterol and high blood pressure that predisposes one for cardiovascular disease, and low plasma testosterone.18,44 A clinical study demonstrated that men with low testosterone levels are twice as insulin resistant as their counterparts with normal testosterone levels, and 90% met the criteria for the metabolic syndrome.45

There also appears to be an inverse relationship between low testosterone levels and diabetes in men.46 Men with diabetes have lower testosterone levels compared to men without a history of diabetes.47 The Third National Health and Nutrition survey of 1,413 men showed that men initially ranked in the lowest one-third with respect to either free or bioavailable testosterone were approximately four times more likely to have prevalent diabetes compared with those ranked in the top one-third, after researchers adjusted the results for age, race/ethnicity, and adiposity.48

Cardiovascular Health

While conventional thought has been that because more men die from heart attacks than women, the disparity must have something to do with testosterone. However, research is pointing out that, in fact, the opposite may be true. Low levels of testosterone appear to be correlated with several cardiovascular risk factors, including atherogenic lipid profiles, insulin resistance, obesity, and a propensity to clot.49 In addition, recent research is showing a clear relationship between low testosterone levels and increased incidence of cardiovascular disease and mortality in men.2

Prostate Health

Compared to younger men, older males have much more estradiol (a potent form of estrogen) than free testosterone circulating in the body. These rising estrogen and declining androgen levels are even more sharply defined in the prostate gland.

Estrogen levels increase significantly in the prostate with age, and estrogen levels in prostate gland tissues rise even higher in men who have BPH.50-52

An important study indicates that testosterone is beneficial for the prostate gland in the vast majority of cases. In this study researchers looked at multiple parameters, including prostate volume, prostate-specific antigen (PSA) levels, and lower urinary tract symptoms in a group of men with low or low-normal testosterone levels.53 Of the 207 men studied, 187 responded favorably to testosterone treatment.

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