Reduced levels of anabolic hormones can contribute to aging and frailty. Most studies that have investigated this focused on the relationship between individual hormones and specific age-associated diseases. An interesting study in older women aged 70-79 years sought to examine the associations of individual anabolic hormonal deficiencies of free testosterone, IGF-1 and DHEA, and to assess their combined effects as well.[1]

Many studies have highlighted the importance of investigating all major hormones, and correcting deficiencies and imbalances if present.[1-8] Given the known mechanisms of testosterone and GH/IGF-1 in building muscle (and possibly also DHEA in elderly) it is reasonable that age-related low levels of anabolic hormones contribute over time to sarcopenia and frailty.[1, 2, 4, 7, 9, 10]

Thus, multiple small effects in aggregate can lead to adverse loss of muscle and disability. In this scenario, if replacement was to occur, it would require lower doses of multiple anabolic hormones. An added benefit to this approach would be fewer side effects from the use of lower hormone doses [11]. In addition, multiple anabolic hormone replacement might also have beneficial additive or even synergistic effects.[11-13]

A notable study investigated whether supplementation with testosterone and GH together, in physiological doses, results in greater improvements in body composition and muscle performance in older men, compared to testosterone supplementation alone...

Study shows only a combination of testosterone therapy and strength training results in an increase in both mechanical muscle function and muscle mass (LBM).

OBJECTIVES:

To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo controlled 24-week study.

Testosterone levels in women decline steeply with age during the reproductive years; by the time women reach their late 40, their blood testosterone levels are approximately half what they were in their 20s.[1, 2]

"It is dangerous to be right when the government is wrong." - Voltaire

For reasons that are not readily apparent, there appears to be a conservative political movement that opposes the use of testosterone in older men. This was clearly demonstrated by the report of the Institute of Medicine, which felt that testosterone is not yet ready for prime time and that there is still a need for studies to prove its efficacy [1]. Along the same lines, the guidelines of the Endocrine Society on testosterone use in older men seem to be ultra-cautious [2]. But fortunately, there are also other, more liberal guidelines and recommendations [3-5].

Probably no other medical issue has been bombarded by the influx of “expert” views from all walks of life; from endocrinologists and psychiatrists to urological surgeons and gerontologists, from the lay press to the regulatory agencies and from the pharmaceutical to the entertainment industries. The dismal result of all this free-for all cacophony of opinions is a great deal of confusion, erroneous information and significant detriment to patients and physicians alike.

Let's take an in-depth look at the reasons for the negative attitudes to male testosterone replacement therapy (I will cover post-menopausal testosterone replacement in an upcoming article), and the hard scientific data that refutes it...

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]

We previously posted a commentary on the recently published and notoriously flawed study which concluded that TRT increases risk for heart attack.

Does Testosterone Therapy Really Increase the Risk of Heart Attack?

http://www.agelessforever.net/anti-aging-news-articles/entry/does-testosterone-therapy-really-increase-the-risk-of-heart-attack

This is the study which caused the media debates:

January 29th issue, the Scientific Journal PLOS (Public Library of Science) ONE published the article: 

"Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men."

Here we have gathered commentaries from other medical professionals, all in one place:

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...

A few days ago, Jan 29th 2014, a controversial study [1] was published showing that men aged 65 years and older, had a two-fold increase in the risk of heart attack in the 90 days after filling an initial TT

prescription, regardless of cardiovascular disease history. Among younger men below 65 years of age with a history of heart disease, the study reported two to three-fold increased risk of MI in the 90 days following an initial TT prescription. 

This study has stirred up heated discussions and media headlines. Let's dissect it and look under the hood...