Life Extension Magazine®
As men age, many become trapped in a vicious cycle that leads to life-threatening abdominal obesity. No matter how much they exercise or how little they eat, these men are unable to shed this excess weight that accumulates in their belly. Published studies have shown that low testosterone and obesity reinforce each other, trapping men in a spiral of weight gain and hormonal imbalance.1-5 In spite of this widespread threat to men’s health, most physicians do not test for testosterone levels in their obese male patients. If they did, millions of men could be protected against the scourge of metabolic syndrome, type 2 diabetes, high blood pressure, atherosclerosis, and cancer. If you happen to be one of these plagued men, please have your testosterone blood levels measured and share the results with your doctor. This article describes the science linking testosterone insufficiency to weight gain and its deadly cousin, the metabolic syndrome. You’ll learn how testosterone determines body composition and fat accumulation. You’ll read why experts now recommend testosterone testing for most men of middle age and beyond. And you’ll see compelling evidence for the role of testosterone therapy as a means of promoting weight loss. Testosterone RulesThroughout our lives, sex hormones controls how we look, feel, and even think. Studies in the past few years show that low testosterone levels are strongly correlated with obesity and the metabolic syndrome in men.1 In fact, there’s now compelling evidence that low testosterone levels are not only markers for developing the metabolic syndrome, but that they are likely to be part of the cause.2,3 Those findings have led experts to strongly recommend testosterone blood testing in most older men, and especially those with type 2 diabetes or the metabolic syndrome.1,4,5 And many are recommending supplemental testosterone as a way of fending off obesity, insulin resistance, and the other components of the metabolic syndrome.6-8 Let’s examine these findings and recommendations carefully, to help men decide if testing and testosterone treatment might be right for them. Reversing a Longstanding RelationshipIt’s long been clear that obesity and the metabolic syndrome are linked to low testosterone levels; the question has been which is cause and which is effect.9 The traditional view was that obesity came first, and that low testosterone was simply the result. That makes sense, because fat tissue is an extremely active hormonal modulator, particularly for testosterone and estrogen. An enzyme in fat tissue known as aromatase converts testosterone into estradiol, the major estrogen in humans. Excess aromatase activity decreases testosterone and increases estrogen levels, resulting in a host of deleterious body changes for men.10,11 Low serum testosterone concentrations are closely correlated with high body mass index (BMI), along with elevated ratios of body fat to lean mass.12,13 But we’re learning that this is only half of the story. Abundant evidence developed over the past few years now shows that, while obesity does cause low testosterone, low testosterone causes obesity. Indeed, low testosterone levels may be among the earliest detectable signs that a man is undergoing the bodily changes that will later become apparent as obesity and the metabolic syndrome.2 An early clue was provided by studies of men undergoing testosterone-lowering androgen deprivation therapies for prostate cancer. Reducing men’s testosterone levels decreased insulin sensitivity and increased body fat mass.14 In one study, more than 50% of men undergoing long-term androgen deprivation therapy developed the metabolic syndrome, manifested in particular by increased abdominal obesity and elevated blood sugar.15 And men who have lost their testicles to cancer generally develop increased BMI and are at elevated risk for the metabolic syndrome.16 Conversely, men who receive testosterone replacement therapy for hypogonadism (diminished testosterone production) experience slower progression from metabolic syndrome to diabetes or cardiovascular disease.17 In those men, testosterone has beneficial effects on insulin regulation, lipid profiles, and blood pressure.17 And in healthy aging men, higher natural testosterone levels are associated with higher insulin sensitivity and a reduced risk of developing the metabolic syndrome.18 Declining Testosterone Levels—Why We Find It So Hard to Lose WeightBeginning in middle age, men’s testosterone levels begin a steady decline, culminating in the so-called “andropause,” a state defined as partial androgen deficiency.19,20 On the same time-scale, men begin to gain weight as fat, and to lose lean muscle mass. It’s now abundantly clear that these two parallel processes are related—that is, the decline in testosterone levels is a direct cause of middle-aged men’s “battle of the bulge.”21 That’s a literal statement: age-associated testosterone decline is closely associated with deposition of deep abdominal fat, a component of the metabolic syndrome.22 But how does testosterone affect obesity and metabolism? In fact, testosterone, like most hormones, has multiple target tissues, and a correspondingly large and diverse set of effects. We now understand, for example, that testosterone plays a vital role in how our bodies balance glucose, insulin, and fat metabolism.23 One mechanism is its powerful stimulation of insulin sensitivity in men, which can have a major impact when levels fall.24 In fact, experts now recognize low testosterone levels as an independent risk factor for insulin resistance (“pre-diabetes”), type 2 diabetes itself, and the full-blown metabolic syndrome with all of its consequences.25-28 Declining testosterone levels are also closely linked to a steady rise in markers of inflammation such as C-reactive protein (CRP).29 Inflammation plays a critical role in development of obesity and many of its related conditions such as atherosclerosis and cancer. And inflammation is also intimately involved in insulin resistance and type 2 diabetes.29 At the same time, the fat deposited as a result of a testosterone deficiency pumps out increasing levels of inflammatory cytokines. That fuels the cycle of inflammation, insulin resistance, and cardiovascular disease that constitutes the metabolic syndrome.30 Together, these findings demonstrate the intimate relationships between testosterone and a host of chronic conditions. Indeed, current thinking is that many of the typical ailments of older men, such as atherosclerosis, hypertension, diabetes, lower urinary tract symptoms, and erectile dysfunction are not in fact separate and distinct entities.23 Rather, they are seen as being integrally related through their dependence on testosterone levels. That’s a radical shift in the way we should be thinking about men’s health!
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Testosterone Levels—Early Warning of Impending DisasterThe association of declining testosterone levels with obesity, the metabolic syndrome, and cardiovascular disease is so strong that many experts now recommend checking testosterone levels to provide early warning of the metabolic syndrome.1 Testosterone deficiency has been found to be a significant and independent risk factor for metabolic syndrome, even in non-obese older men.31 It causes not only increased fat mass, but also triggers elevations in fasting insulin levels, a late marker of developing metabolic syndrome.7,32 The association of low testosterone levels with metabolic syndrome is independent of age—that is, even younger men with low testosterone are immediately at increased risk for the syndrome.33 Somewhat surprisingly, the association is also independent of BMI, pointing to testosterone’s multiple effects on regulation of glucose, insulin, and lipid metabolism.34 It has recently been proposed, in fact, that low testosterone levels be included in the very definition of the metabolic syndrome, because of the consistency with which it occurs.35 There’s an obvious implication here. Subtle deficiencies in testosterone may be present long before obesity and other more obvious manifestations of the metabolic syndrome become evident.34 That makes it vital for all men, not just the overweight or obese, to have testosterone levels checked regularly by a reliable laboratory. Be sure that both total testosterone and free testosterone are ordered—both have been associated with metabolic syndrome.35 When having your blood tested for total and free testosterone, make sure you also order tests for PSA to rule out existing prostate cancer, estradiol to determine whether you need to take an aromatase inhibiting drug in case estrogen levels are too high, and a CBC/chemistry test to measure liver function and blood cell counts. Restoring Healthy Testosterone LevelsWhat should you do if your testosterone level comes back low? There’s a growing body of evidence suggesting that careful testosterone replacement therapy is protective against many features of the metabolic syndrome and can enhance blood sugar control.36 Given early enough, testosterone therapy may slow or even halt the progression from early metabolic syndrome to diabetes or cardiovascular disease.17 In one study of diabetic men with low testosterone, oral treatment improved their glucose control and decreased their abdominal obesity. A beneficial side effect was reduction in erectile dysfunction.6 Other placebo-controlled studies have shown decreases in whole body, total, and subcutaneous abdominal fat mass, accompanied by increases in lean body mass, as a result of testosterone therapy.8 There’s a growing body of evidence suggesting that careful testosterone replacement therapy is protective against many features of the metabolic syndrome and can enhance blood sugar control. Of course it’s important to check and to follow testosterone levels when considering treatment. Achieving testosterone levels within the existing reference ranges may not be sufficient to combat obesity and metabolic syndrome. Some testosterone-dependent biological functions require higher levels than others, and those thresholds differ among men.37 Finally, a word about testosterone therapy and the risk of prostate cancer. For decades we believed (and some still do) that higher serum testosterone concentrations contribute to the risk of prostate cancer. More recently, considerable data have emerged suggesting a more complex picture, and indicating that in fact testosterone therapy may not be nearly as risky as once assumed.38 In fact, according to Dr. Abraham Morgentaler of Harvard’s Beth Israel Deaconess Medical Center, “One of the more interesting changes over the last several years has been the growing acceptance of the use of testosterone therapy in men with a prior history of prostate cancer, with early data indicating minimal risk of cancer recurrence or progression.”38 Other experts in the field agree that the risks of testosterone therapy are often exaggerated and should not outweigh the benefits of treatment.21 Indeed, Dr. Morgentaler goes on to note, new evidence suggests that it is not high, but low serum testosterone that is responsible for many features of prostate cancer risk.38 Since we now know that low testosterone causes obesity, and we further know that obesity is a risk factor for cancer,39,40 there is certainly a logical basis for the idea that low testosterone is indirectly a cancer risk factor. SummaryTestosterone and body fat content have an intricate and bidirectional relationship. Excess body fat causes low testosterone, but low testosterone also causes excess body fat. Testosterone regulates many facets of energy balance, with an especially powerful impact on glucose, insulin, and fat metabolism. The deadly results of low testosterone therefore exceed simply causing obesity. Low testosterone also dramatically raises men’s risk for the metabolic syndrome, a major health threat for anyone at or beyond middle age. Experts now recommend regular testing for any man at risk for low testosterone, including aging men.1 If your testosterone levels prove to be low, you should consider testosterone treatment in consultation with a physician. If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027. | ||
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