Ageless Forever Anti-Aging News Blog

Testosterone Replacement Therapy (TRT) in Testosterone Deficient men - effects on fat loss, waist reduction and metabolic syndrome components

Testosterone deficiency in men, aka hypogonadism, is associated with increased total and abdominal fat mass, and reduced muscle mass, which negatively impacts body composition.[1, 2] This contributes to development of risk factors like insulin resistance, chronic inflammation, and atherogenic dyslipidemia (a triad of increased blood levels of small, dense LDL particles and triglycerides, and decreased levels of HDL particles), which increase the risk for cardiovascular disease, metabolic syndrome and diabetes.[1, 3-16]

Previous studies have shown that testosterone replacement therapy ameliorates these risk factors in testosterone deficient (hypogonadal) men; it increases insulin sensitivity [17-20] and HDL (the "good" cholesterol) [9, 10, 20, 21], and reduces waist circumference [9, 20, 22], fasting blood glucose [9, 20] triglycerides (blood fats)[9], LDL (the "bad" cholesterol) [19, 22-24], and several inflammatory markers.[17, 25]

A 2011 meta-analysis concluded that testosterone replacement therapy improves metabolic control, as well as reduces abdominal obesity.[9] Many studies have shown that testosterone replacement therapy in hypogonadal men increases muscle mass and reduces fat mass.[19, 26-32] Further, adding testosterone (50 mg/day for 1 year, administered as a transdermal gel) to a diet and exercise program results in greater therapeutic improvements of glycemic control and reverses the metabolic syndrome.[20]

Testosterone also has direct (non-obesity mediated) beneficial effects on many metabolic and cardiovascular risk factors [12, 33-37], and reduces death risk independently of body fat status.[38] In line with all these effects, low testosterone levels are associated with increased risk of cardiovascular complications [39], and all-cause and cardiovascular disease death [40-42]. Low testosterone may thus be a predictive marker for men at high risk of cardiovascular disease.[41] In a group of men aged 50-91 who were followed for 20 years, it was found that men whose total testosterone levels were in the lowest quartile (241 ng/dl or lower) were 40% more likely to die than those with higher levels, independent of age, adiposity, lifestyle or presence of cardiovascular risk factors.[38]

Thus, treatment of testosterone deficient men with testosterone has demonstrated considerable health benefits. Despite this, critics state that most of the studies on testosterone replacement therapy were too small. They also argue that the studies were of too short duration (most of them lasting 6-12 months), and that the long-term effects of testosterone on body composition are not known.

Two 5 year long studies were just published that addressed the duration and small study size shortcomings in previous research...

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Effects of 6-year Long-Term Testosterone Replacement Therapy (TRT) in Patients with ‘‘Diabesity’’

March 6th 2014 FDA approved Aveed for treatment of male hypogonadism, aka testosterone deficiency.[1] Aveed is a long-acting form of injectable testosterone called testosterone undecanoate. In Europe, testosterone undecanoate (under the name Nebido) has a long successful TRT track record for treatment of testosterone deficiency and its consequences (especially obesity, the metabolic syndrome and diabetes).[2-16]

In contrast to shorter acting forms of testosterone (e.g. cypionate), testosterone undecanoate only needs to be injected every 6 to 12 weeks, and thereby offers practical benefits to patients. (Comment: for Nebido (1000 mg per 4 ml) the initial interval is 6 weeks, followed by intervals of 10-14 weeks; for Aveed (750 mg per 3 ml) the initial interval is 4 weeks, followed by 10-week intervals). 

Five days after the FDA approval a notable and impressive 6-year long TRT study was published, confirming the health benefits of TRT that have previously been found in shorter term studies... [44]

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Watch Your Waist - it may shorten your life!

Your waistline not only makes or breaks your esthetic appearance; if you belly gets too large, it may greatly jeopardize your health and even longevity.

Waist circumference strongly correlates with abdominal obesity and is the most commonly used measure of body fat distribution.[1, 2] Many studies have found enlarged waist circumferences to be associated with all-cause mortality, in most cases independently of general obesity.[3-11]

Abdominal obesity (aka visceral obesity) appears to be more strongly associated with multiple chronic diseases than is gluteo-femoral obesity (fat deposition around the butt and thighs).[1] Increased waist circumference confers a health risk even in normal weight people.[12]

A notable large study investigated the association of waist circumference with mortality using intuitive 2 in (5 cm) increments for men and women, and also evaluated risk within narrow categories of body fatness (BMI). In addition, the study estimated years of life lost due to a large waist circumference.[13]


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Testosterone Therapy Prevents Gain in Intra-Abdominal Fat and Counteracts Loss of Muscle in Non-Obese Aging Men

Testosterone deficiency is especially common in men who are obese and/or have the metabolic syndrome or diabetes, with a prevalence ranging from 35% to almost 80%.[1-5] However, there is a subgroup of non-obese men who have low testosterone levels and suffer from typical symptoms of low-T, but who do not (yet) have any co-morbidities. 
 
Many studies show that suboptimal testosterone levels may contribute to the development of obesity (including abdominal obesity) [6, 7], metabolic syndrome [8-13] and/or diabetes.[9, 14-20] Therefore, testosterone therapy in non-obese men with testosterone deficiency may be an effective intervention to correct not only symptoms associated with hypogonadism, but also prevent the development of obesity, metabolic syndrome and/or diabetes.
 
A notable study was set out to specifically investigate this…
 
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Effects of long-term testosterone treatment on weight loss and waist size in obese men - is TRT the next obesity treatment?

Testosterone, historically believed to be important only for male reproduction and sexuality, has over the past decades transformed from niche hormone to multi-system player.[1] A rapidly accumulating body of research is showing that testosterone is an important metabolic hormone with marked effects on energy metabolism and body composition.[2]
 
In USA, 36% of the adult population are obese (BMI >30), (affecting a similar proportion of men and women) [3], and obesity prevalence is escalating worldwide. According to the McKinsey Global Institute (MGI) report “Overcoming obesity: An initial economic analysis”, obesity is “one of the top three preventable social burdens (along with smoking and violence/war/terrorism) generated by human beings” imposing an estimated annual global direct economic burden amounting to 2 trillion USD.[4] 
 
Obesity treatments with comprehensive lifestyle modification and/or drugs are notorious for their poor long-term efficacy and inability to achieve long-term weight loss maintenance.[5-9] Even with continued lifestyle treatment, significant weight regain occurs.[7, 9, 10] And obesity drugs have side effects which limit their long-term and widespread use. [11, 12] Therefore, new interventions are urgently needed to combat this alarming preventable threat to society. 
 
Here I summarize a recent study that investigated the effects of long-term testosterone treatment – up to 8 years - on weight loss and waist size in 411 testosterone deficient men with obesity classes I-III.[13]
 
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Real-life experience of continuous long-term testosterone therapy on anthropometric, endocrine and metabolic parameters for up to 10 years

While it is well documented that testosterone levels decline in aging men, recent studies show that in some cases obesity and impaired general health can be more influential causes of testosterone deficiency than chronological age and aging per se.[1, 2]
 
Here I present real-life results from a registry study which investigated the effects of continuous long-term testosterone therapy for up to 10 years on anthropometric (body measurements), endocrine and metabolic parameters in obese hypogonadal men.[3]
 
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Watch Your Belly – not just to look good!

Over the past two decades it has been established beyond any doubt that the amount of fat around the waist (aka abdominal fat and visceral fat) is at least as important, if not more important, than the total amount of body fat in predicting and /or causing complications that have been traditionally associated with overweight/obesity.[1]
 
Abdominal obesity is a strong risk factor for cardiovascular disease independent of BMI (a proxy for obesity) [2, 3] and is thought to affect disease risk through increased insulin resistance.[4, 5]  Actually, the common development of insulin resistance with aging is caused by growing bellies, rather than aging per se.[6] Notably, normal-weight abdominal obesity is associated with higher mortality than generalized obesity (as defined by BMI).[7]
 
An enlarged belly is an especially strong indicator of metabolic risk in men.[8, 9] People with large a waist circumference – i.e. those having a belly - have an increased risk of cardiovascular disease, diabetes and cancer, compared to those with smaller waist circumferences, regardless of BMI. [10-14] Your waist also impacts your longevity, which I covered in a previous article "Watch Your Waist - it may shorten your life!"
 
And your belly can interfere with your sex life...
 
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Young Men, Waist, Testosterone and Erectile Function: Low-T is not only an old man's issue

Most people, including traditional doctors, think that testosterone deficiency is an old man’s issue. This is very wrong! Actually, an excess amount of body fat can cause a man’s testosterone levels drop to as much as 10 years of aging.[1]
 
Several studies have demonstrated that too much body fat is associated with reduced testosterone levels independent of aging.[2-4]
 
Low levels of testosterone (both total and free testosterone) are a consistent feature among young men below 40 years of age with metabolic syndrome, the hallmark of which is an enlarged belly.[5]
 
Young men (20–39 years) with the lowest baseline total testosterone levels have the highest risk of developing cholesterol and blood fat abnormalities (dyslipidemia). [6] Compared to age-matched men with the highest baseline total testosterone levels of 663 ng/dL or higher, those with the lowest baseline total testosterone levels of 418 ng/dL or below had up to a twofold greater risk of developing an adverse lipid profile 5 years later, which in turn could contribute to future risk of cardiovascular disease.[6]
 
Thus, testosterone deficiency clearly has health implications also for younger men. But how much does your belly actually impact your testosterone levels… and erectile function?
 
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Waist-to-Height Ratio as a Screening Tool for Testosterone Deficiency

A bidirectional relationship exists between excess body fat, and/or belly fat, and testosterone levels in men. That is, excess body (belly) fat decreases testosterone levels and may cause testosterone deficiency, and low testosterone levels increases body (belly) fat.[1-4]  I covered this in-depth in a previous article “Testosterone and Fat Loss - the Evidence”.
 
In “Keep your waist to less than half your height” I introduced the waist-to-height ratio and explained that it is a better tool for predicting health outcomes and mortality than is waist circumference alone. I have also covered the association between a large waist (i.e. belly) and reduced testosterone levels in "Young Men, Waist, Testosterone and Erectile Function: Low-T is not only an old man's issue".
 
Here I will summarize research showing that the waist-to-height ratio can also be used as a screening tool for testosterone deficiency. 
 
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