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    Default Real-life Experience of Continuous Long-term Testosterone Therapy

    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]

    Key Points
    – In this prospective registry study, 115 hypogonadal men, mean age 59 years, received injections with testosterone undecanoate (brand name Aveed in USA and Nebido in Europe) in 12-week intervals for up to 10 years.

    – Body weight and waist circumference decreased from 97.3 to 84.6 kg and from 107 to 92 cm, respectively.

    – Fasting glucose, HbA1c, and the triglyceride:HDL ratio (a surrogate marker of insulin resistance) declined.

    – Lipid profile significantly improved, with an increase in HDL levels, decrease in total cholesterol:HDL ratio, and marked reduction in non-HDL cholesterol and remnant cholesterol.

    – Reductions in systolic and diastolic blood pressure, and inflammation (measured by C-reactive protein) were also seen.

    – No major adverse cardiovascular events were observed throughout the study.

    What is known
    Testosterone deficiency is associated with substantially higher risks of all-cause and cardiovascular mortality [4, 5], and normalization of testosterone levels with testosterone therapy reduces incidence of myocardial infarction and mortality, both in diabetic [6, 7] and non-diabetic men.[8, 9]

    Risk factors for testosterone deficiency include obesity, advanced age, the metabolic syndrome and a poor general health status.[10] Among these, obesity is an especially strong risk factor for testosterone deficiency.[1, 2] In addition, testosterone deficiency is a risk factor for obesity. This creates a vicious circle where obesity feeds testosterone deficiency and testosterone deficiency feeds obesity.

    Testosterone therapy has a number of beneficial metabolic effects and improves body composition, body fat distribution and metabolic factors [11-13], and thus may be a powerful tool in breaking the obesity-hypogonadal obesity cycle.

    What this study adds
    In this registry study, 1000 mg injections of testosterone undecanoate in 12-week intervals were continuously given to 115 men with a maximal follow-up of 10 years. The composition of these patients was as follows: 115 men were treated for a minimum of 4 years, 114 for 5 years, 97 for 6 years, 70 for 7 years, 57 for 8 years, 48 for 9 years and 23 for 10 years. Mean treatment time was 7.6 years.

    Total testosterone levels increased from 226 ng/dL (7.8 nmol/L) to trough levels (measured prior to the following injection) of 568 ng/dL (19.7 nmol/L), free T increased from 144.8 to 461.1 pmol/L, and SHBG decreased from 40.1 to 33.1 nmol/L.

    Waist circumference decreased progressively from 42 to 36 inches (107 to 92 cm). The decrease was significant vs baseline and significant vs previous year for the first 7 years. The reduction in waist circumference was 12%. Body weight decreased from 215 to 187 lb (97.3 to 84.6 kg). The decrease was statistically significant vs baseline (P < 0.0001) and significant vs previous year for the first 8 years. Weight reduction was progressive and amounted to 18.5% (minimum - 6.2% and maximum - 32%) after 10 years. There were major improvements in the lipid profile. The total cholesterol:HDL ratio – a cardiovascular risk marker [14] - improved from 6.6 to 3.1. The triglyceride:HDL ratio, a surrogate marker of insulin resistance [15], improved from 6.2 to 2.8.

    Figure 1: Absolute changes in cholesterol / lipids with testosterone therapy for up to 10
    years.
    Yassin-2016_10-yr-registry-study_fig1.jpg



    Figure 2: Relative changes in cholesterol / lipids with testosterone therapy for up to 10 years.

    Yassin-2016_10-yr-registry-study-percent-change_fig2.jpg

    Systolic blood pressure decreased from 135 to 120 mmHg, and diastolic blood pressure decreased from 83 to 74 mmHg. A decline in CRP from 1.39 to 0.62 mg/dL was also observed.

    Fasting glucose decreased from 111 to 77 mg/dL, with the main reduction occurring during the first treatment year. HbA1c declined from 6.4 to 5.4%. No major adverse cardiac event occurred during the entire observation time.

    Comments
    Two particularly notable results in this study are the marked reductions in non-HDL cholesterol and remnant cholesterol. For a primer on this, see my previous article “Remnant Cholesterol and non-HDL – What’s that? Why bother?”

    non-HDL levels dropped from 208 mg/dL to 167 mg/dL after 1 year of testosterone therapy and to 116 mg/dL after 10 years of testosterone therapy. This is a reduction of 20% and 45%, respectively. LDL-C dropped from 157 mg/dL to 136 mg/dL to 98 mg/dL, with corresponding percentage reductions of -14% to -37%.

    Another result from this study to be highlighted is the reduction in remnant cholesterol levels, which dropped from 52 to 13-17 mg/dL. This corresponds to a reduction of -38% after 1 year and -66% after 10 years. This reduction was markedly greater than that of both LDL and non-HDL, and is due to the high baseline level of triglyceries (blood fat), which was also markedly reduced (see table 1 and 2).

    This shows that testosterone therapy has a greater beneficial effect on non-HDL and especially on remnant cholesterol levels, than LDL (aka, “bad’ cholesterol, the old school traditional treatment target). Hence, when evaluating the effectiveness of testosterone therapy on the lipid profile, attention should be given to non-HDL, and especially remnant cholesterol. The marked improvements in remnant cholesterol with testosterone therapy likely explain – possibly to a large part – the reduction in mortality that has been observed with testosterone therapy.[6, 7, 9]

    Real-life results
    Another notable aspect of this study is its real-life nature. It is widely accepted that the randomized controlled trial (RCT) is the gold standard for demonstrating the efficacy of a given therapy (i.e. effect under ideal circumstances). Real-life studies, on the other hand, complement this by demonstrating effectiveness (i.e. true benefit to patients in routine practice).[16]

    Applicability of RCT results to daily linical practice can be limited for several reasons; the patients selected to participate in RCTs may be different from those in routine practice, and RCTs may not detect chronic toxicities, especially those occurring in patients with comorbidities or that only emerge following prolonged therapy.

    This real-life study fills the important gap in applicability of RCT results to daily clinical practice by providing evidence for both effectiveness and safety, as well as highlighting marked benefits on new cholesterol/lipid outcomes that are now being endorsed by major cardiovascular disease treatment guidelines.
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    good info
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    It is good info. I would love to see a study of otherwise "normal", healthy guys with low testosterone over some extended period. There are enough of us out there - out here, I guess I should say - that it shouldn't be a problem finding subjects!

    One thing I've never seen addressed in any of the numerous studies I've read on this subject is something that the doc who prescribes my test has warned me about. That is the increased risk of stroke. According to him, it isn't known what exactly the cause is, but that TRT does increase the risk. Anyone hear of this and know anything about it?
     

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    Quote Originally Posted by EMW14 View Post
    It is good info. I would love to see a study of otherwise "normal", healthy guys with low testosterone over some extended period. There are enough of us out there - out here, I guess I should say - that it shouldn't be a problem finding subjects!

    One thing I've never seen addressed in any of the numerous studies I've read on this subject is something that the doc who prescribes my test has warned me about. That is the increased risk of stroke. According to him, it isn't known what exactly the cause is, but that TRT does increase the risk. Anyone hear of this and know anything about it?
    Polycythemia which they say is a common occurence or disorder that arises in men who are on trt or hrt , due to the increased hemoglobin which in turn causes a thickening of the blood, slower moving blood flow tends to cause or create a better chance of clotting, and on top of this testosterone has been found to increase the production of the lipid thrombane or some something like that, this is the narrowing of the blood vessels , so between the slower moving blood and narrowing of the blood vessels, you have a pretty good recipe for clotting which leads to stroke
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    my copay for this information is 20$ lol,
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    Lol. Good info there, Presser. All that seems to explain why my blood pressure goes up a little being on trt.
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    Quote Originally Posted by EMW14 View Post
    Lol. Good info there, Presser. All that seems to explain why my blood pressure goes up a little being on trt.
    What about the copay though lol
    Real-life Experience of Continuous Long-term Testosterone Therapy

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