Androgen Replacement

[Michael Scally MD]

[OA] Burden of Male Hypogonadism and Major Comorbidities, and the Clinical, Economic, and Humanistic Benefits of Testosterone Therapy

Male hypogonadism and major comorbidities such as type 2 diabetes mellitus, obesity, cardiovascular disease, and osteoporosis appear closely connected, forming a vicious cycle that leads to further hypogonadism. This narrative review provides a comprehensive overview of the current literature on the overall burden of male hypogonadism alongside related comorbidities, and how this may be alleviated through testosterone therapy.

Observational and clinical data demonstrate that the interaction of male hypogonadism and its related comorbidities is associated with increased mortality, cardiovascular event risk and reduced quality of life. Evidence from epidemiological and registry-based studies shows that this clinical and humanistic burden translates to increased economic burden on health-care systems, through increased physician visits, medical claims, and drug costs.

Male hypogonadism can be managed with testosterone therapy, which is intended to normalize testosterone concentrations and thereby reduce both hypogonadism symptoms and risk of comorbidities. Clinical and observational data suggest that in males with hypogonadism, testosterone therapy rapidly and sustainably improves glycemia, reduces risk of progression to diabetes, leads to significantly reduced waist circumference and fat mass, while providing significant positive effects on cardiovascular event risk and bone density. Significant and sustained improvement in patient-reported erectile function, urinary function, and aging male symptoms have also been shown.

Economic evaluations have estimated that reduced comorbidity risk following testosterone therapy may lead to cost-savings, with one study estimating yearly inpatient savings of £3732 for treating comorbidities after intervention.

A major unmet need exists in the area of male hypogonadism, particularly related to common comorbidities. Options for treatment include testosterone therapy, which has been shown to alleviate the clinical, economic, and humanistic burden associated with these conditions. As the prevalence of male hypogonadism is likely to increase globally, and this condition may be currently underdiagnosed, cost-saving testosterone therapies should be increasingly considered to manage hypogonadism.

Yeo S, Holl K, Peñaherrera N, Wissinger U, Anstee K, Wyn R. Burden of Male Hypogonadism and Major Comorbidities, and the Clinical, Economic, and Humanistic Benefits of Testosterone Therapy: A Narrative Review. Clinicoecon Outcomes Res. 2021 Jan 12;13:31-38. doi: 10.2147/CEOR.S285434. PMID: 33488103; PMCID: PMC7814241. Burden of Male Hypogonadism and Major Comorbidities, and the Clinical, | CEOR

 

[Michael Scally MD]

[OA] Testosterone Replacement In Aging Men: An Evidence-Based Patient-Centric Perspective

The deluge of advertisements marketing erectile dysfunction medications and testosterone products has empowered many older men to seek medical help for their sexual and genitourinary problems. As a reflection of this historical transition toward increased attention on men’s sexual health, men’s health clinics have sprung up across the United States; concomitantly, testosterone prescription sales increased from about $100 million US dollars in the year 2000 to nearly $2.7 billion in 2013.

Today, a majority of testosterone prescriptions are written for men aged 40–64 years even though testosterone is not approved by the US Food and Drug Administration (FDA) for age-related decline in testosterone. Citing the lack of data on long-term benefits and risks of testosterone treatment in older men with age-related decline, the FDA has sounded alarm over the growing off-label use of testosterone.

Experts have debated whether prescribing testosterone to older men with testosterone deficiency is disease mongering or whether subsets of older men with testosterone deficiency might benefit from testosterone treatment. Fortunately, several recent randomized controlled trials (RCTs) have provided important information on the efficacy and short-term safety of testosterone treatment in older men.

This Viewpoint synthesizes data from epidemiologic studies and RCTs and offers a perspective on a patient-centric approach to treatment decision in older men with testosterone deficiency based on an individualized assessment of benefits and risks.

Bhasin S. Testosterone replacement in aging men: an evidence-based patient-centric perspective. J Clin Invest. 2021 Feb 15;131(4):146607. doi: 10.1172/JCI146607. PMID: 33586676. JCI - Testosterone replacement in aging men: an evidence-based patient-centric perspective

 

[Michael Scally MD]

[OA] Association of Daily Step Count and Serum Testosterone

Purpose: To describe the association between daily activity (i.e., daily step counts and accelerometer intensity measures) and serum TT levels in a representative sample of US adults aged 18 years or older.

Methods: A retrospective cohort study was carried out utilizing the NHANES (National Health and Nutrition Examination Survey) 2003-2004 cycle. Physical activity was measured with a waist-worn uniaxial accelerometer (AM-7164; ActiGraph) for up to 7 days using a standardized protocol. Using linear and multivariable logistic regression controlling for relevant social, demographic, lifestyle, and comorbidity characteristics, we assessed the association between daily step counts and TT.

Results: A total of 279 subjects with a median age 46 (IQR: 33-56) were included in the analysis. 23.3% of the cohort had a low serum TT level (TT < 350 ng/dl). Compared to men who took <4000 steps per day, men who took >4000 or >8000 steps/day had a lower odd of being hypogonadal (OR 0.14, 95% CI: 0.07-0.49 and 0.08, 95%CI: 0.02-0.44, respectively). While a threshold effect was noted on average, TT increased 7 ng/dL for each additional 1000 steps taken daily (β-estimate: 0.007, 95% CI: 0.002-0.013).

Conclusions: Patients with the lowest daily step counts had higher odds of being hypogonadal. The current work supports a possible association between daily steps, total testosterone, and hypogonadism for men in the US.

Del Giudice F, Glover F, Belladelli F, De Berardinis E, Sciarra A, Salciccia S, Kasman AM, Chen T, Eisenberg ML. Association of daily step count and serum testosterone among men in the United States. Endocrine. 2021 Feb 12. doi: 10.1007/s12020-021-02631-2. Epub ahead of print. PMID: 33580402. Association of daily step count and serum testosterone among men in the United States

 

[Michael Scally MD]

[OA] Prediction of Secondary Testosterone Deficiency Using Machine Learning: Comparative Analysis Of Ensemble And Base Classifiers, Probability Calibration, And Sampling Strategies In A Slightly Imbalanced Dataset

Testosterone is the most important male sex hormone, and its deficiency brings many physical and mental harms. Efficiently identifying individuals with low testosterone is crucial prior to starting proper treatment. However, routine monitoring of testosterone levels can be costly in many regions, resulting in an underreporting of cases, especially in developing countries. Moreover, there are few studies that employ machine learning (ML) in prognosticating testosterone deficiency.

This research, therefore, aims to offer a coherent comparative analysis of machine learning methods that can predict testosterone deficiency without having patients undergo costly medical tests.

In doing so, we seek to provide to the urological community a publicly available dataset (osmarluiz/Testosterone-Deficiency-Dataset) to increase research in this yet untapped field.

For this analysis, we used ten base classifiers (optimized with grid search stratified K-fold Cross Validation); three ensemble methods; and eight sampling strategies to analyze a total of 3,397 patients.

The analysis was based on six features (age; abdominal circumference; triglycerides; high-density lipoprotein; diabetes; and hypertension), all of which obtained by low-cost out-of-pocket exams.

We compared the sampling strategies and the classifiers' performance on an independent test set using ranking (PR-AUC), probabilistic (Brier score), and threshold metrics.

We found that:

(1) within the ranking metrics, sampling strategies did not enhance results in this slightly imbalanced (4:1 ratio) dataset;

(2) the ensemble classifier using weighted average presented the best performance;

(3) the best base classifier was XGBoost; (4) calibration showed significant improvement for the sampling strategies and slight improvements for the no sampling strategy;

(5) the McNemar's test presented statistically similar results among all classifiers; and

(6) abdominal circumference (AC) had by far the highest feature importance, followed by triglycerides (TG).

Age, on the other hand, showed very little significance in predicting testosterone deficiency.

Novaes MT, Ferreira de Carvalho OL, Guimarães Ferreira PH, et al. Prediction Of Secondary Testosterone Deficiency Using Machine Learning: Comparative Analysis Of Ensemble And Base Classifiers, Probability Calibration, And Sampling Strategies In A Slightly Imbalanced Dataset. Informatics in Medicine Unlocked 2021:100538. Prediction Of Secondary Testosterone Deficiency Using Machine Learning: Comparative Analysis Of Ensemble And Base Classifiers, Probability Calibration, And Sampling Strategies In A Slightly Imbalanced Dataset

 

[Michael Scally MD]

Late-Onset Hypogonadism: Clinical Evidence, Biological Aspects and Evolutionary Considerations

Highlights

Testosterone secretion is highly dynamic among species and tailored to the demands of the respective environmental conditions.

Decreasing testosterone levels with age are not restricted to humans, but also found in many other mammals.

A growing demand for testosterone replacement therapy (TRT) in aging men has been noted worldwide.

The benefits of TRT need to be balanced against potential adverse events, which mainly appear to affect the cardiovascular system.

The link between testosterone, cardiovascular health and the risk for the development prostate cancer is incompletely understood.

Testosterone-driven anabolic pathways are in conflict with catabolic programs required for maintenance functions.


The growing life expectancy in modern societies has raised scientific interest in identifying medical interventions to alleviate age-associated pathologies such as vascular calcification, cognitive decline, sarcopenia, osteoporosis and sexual dysfunction.

Although no such single treatment has thus far been established in humans, some clinicians and patients have set their hopes on testosterone replacement therapy (TRT) as a potential "fountain of youth" for aging men. While TRT has proven effective in ameliorating distinct symptoms of late-onset hypogonadism (LOH), its safety remains to be demonstrated.

Besides humans, multiple other species exhibit age-related reductions in circulating testosterone levels, raising the question whether such changes are an inherent, pathological feature of growing organismal age or rather reflect an adaptive response.

In this manuscript, we apply key principles of evolutionary medicine to testosterone biology and LOH to provide a novel perspective on these two fields. Additionally, we discuss insightful data derived from the animal kingdom to illustrate the plasticity of individual testosterone trajectories across the lifespan, outline cost-benefit-considerations of TRT in LOH and highlight potential caveats of such therapies.

Jaschke N, Wang A, Hofbauer LC, Rauner M, Rachner TD. Late-onset hypogonadism: clinical evidence, biological aspects and evolutionary considerations. Ageing Res Rev. 2021 Feb 18:101301. doi: 10.1016/j.arr.2021.101301. Epub ahead of print. PMID: 33610812. Late-onset hypogonadism: clinical evidence, biological aspects and evolutionary considerations

 

[Michael Scally MD]

[OA] Cardiovascular Risk and Testosterone - From Subclinical Atherosclerosis to Lipoprotein Function to Heart Failure

The cardiovascular (CV) benefit and safety of treating low testosterone conditions is a matter of debate. Although testosterone deficiency has been linked to a rise in major adverse CV events, most of the studies on testosterone replacement therapy were not designed to assess CV risk and thus excluded men with advanced heart failure or recent history of myocardial infarction or stroke.

Besides considering observational, interventional and prospective studies, this review article evaluates the impact of testosterone on atherosclerosis process, including lipoprotein functionality, progression of carotid intima media thickness, inflammation, coagulation and thromboembolism, quantification of plaque volume and vascular calcification.

Until adequately powered studies evaluating testosterone effects in hypogonadal men at increased CV risk are available (TRAVERSE trial), clinicians should ponder the use of testosterone in men with atherosclerotic cardiovascular disease and discuss benefit and harms with the patients.

Gencer B, Bonomi M, Adorni MP, Sirtori CR, Mach F, Ruscica M. Cardiovascular risk and testosterone - from subclinical atherosclerosis to lipoprotein function to heart failure. Rev Endocr Metab Disord. 2021 Feb 22. doi: 10.1007/s11154-021-09628-2. Epub ahead of print. PMID: 33616800. Cardiovascular risk and testosterone – from subclinical atherosclerosis to lipoprotein function to heart failure

 

[Michael Scally MD]

[OA] Exogenous Testosterone Replacement Therapy Versus Raising Endogenous Testosterone Levels

Essential points:

The manuscript reviews the available methods of exogenous testosterone replacement therapy which are, but not limited to oral, buccal, intramuscular, transdermal, subdermal, and nasal, respectively.

The manuscript reviews the alternative therapies to increase endogenous testosterone replacement which includes, but not is limited to selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors, respectively.

Furthermore, the review highlights investigational therapies to increase endogenous testosterone such as selective androgen receptor modulators and Leydig stem cell transplantation, respectively.

Moreover, the review compares the core impacts of these therapy options on hormone levels and modulation of HPG axis.


Testosterone replacement therapy is an important treatment option for men with low testosterone and symptomatic hypogonadism. Various formulations of exogenous testosterone replacement therapy exist, including oral, buccal, intramuscular, transdermal, subdermal, and nasal preparations.

However, exogenous testosterone replacement therapy is a double-edged sword, posing risks to fertility due to negative feedback mechanisms on the hypothalamic-pituitary-gonadal (HPG) axis, which is the main regulator of testosterone production and spermatogenesis in males.

Alternative pharmacologic therapies are being used to increase endogenous testosterone levels while attempting to preserve fertility and function of the HPG axis. These include selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors.

This review focuses on overviewing and comparing the currently available methods of exogenous testosterone replacement therapy, alternative treatments to increasing endogenous testosterone, and novel treatments that are currently under investigation to normalize testosterone levels while preserving the function of the HPG axis.

In conclusion, reports suggest that, though Testosterone replacement therapy is an important way to restore testosterone levels and reduce symptoms associated with low testosterone, it is often difficult to decide which treatment to select for patients with testosterone deficiency.

Several factors need to be considered to decide on optimal therapy option for the patient which include but are not limited to safety, efficacy, cost-effectiveness, dosing flexibility, and side effects. Alternative approaches which aim to improve endogenous testosterone production and preserve fertility are promising but still are at their initial stages of development. Ultimately, patient-centered decision making is paramount to appropriate treatment selection.

Khodamoradi K, Khosravizadeh Z, Parmar M, et al. Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: current and future prospects. F S Rev. 2021 Jan;2(1):32-42. doi: 10.1016/j.xfnr.2020.11.001. Epub 2020 Nov 17. PMID: 33615283; PMCID: PMC7894643. https://www.fertstertreviews.org/article/S2666-5719(20)30009-8/fulltext

 

[Millard]

, alternative treatments to increasing endogenous testosterone

What ???

 

[Michael Scally MD]

[OA] Molecular Modeling Study of The Testosterone Metabolizing Enzyme UDP-Glucuronosyltransferase 2B17

The dominant sex hormone testosterone is mainly metabolized by liver enzymes belonging to the uridine-diphospho (UDP) glucuronosyltransferase (UGT) family. These enzymes are the main phase II enzymes, and they have an important role in the detoxification of endogenous and exogenous compounds in humans.

The aim of the present study was to improve the understanding of the binding properties of UGT2B17. A homology modelling procedure was used to generate models of the UGT2B17 enzyme based on templates with known crystal structures. Molecular docking of inhibitors was performed to gain further insights in the interactions between ligand and binding site, and to determine which of the models had the best accuracy. ROC curves were made to evaluate the ability of the models to differentiate between binders (inhibitors) and non-binders (decoys).

When comparing the four models, which were based on four different crystal structures, the model based on the 4AMG crystal structure was the most accurate in distinguishing between true binders and non-binders. Investigating pharmacological UGT2B17 inhibition may provide novel treatment for patients with low testosterone levels.

Such treatment may elevate endogenous testosterone levels and provide a more predictable increase in serum concentrations rather than un-physiological elevation of serum levels through direct treatment with testosterone, and this could be favorable both for giving a predictable treatment regime with reduced chances of serious adverse effects. The present study may serve as a tool in the search for novel drugs aiming for increasing testosterone levels.

Trane I, Sager G, Sveberg Dietrichs E, Westrheim Ravna A. Molecular modeling study of the testosterone metabolizing enzyme UDP-glucuronosyltransferase 2B17. Bioorganic & Medicinal Chemistry 2021:116060. Molecular modeling study of the testosterone metabolizing enzyme UDP-glucuronosyltransferase 2B17

 

[Michael Scally MD]

[OA] Canadian Urological Association Clinical Practice Guideline on Testosterone Deficiency in Men: Evidence-Based Q&A

As part of their ongoing commitment to education and best practice standards, the Canadian Urological Association (CUA) solicited the creation of a clinical practice guideline dedicated to testosterone deficiency (TD) in men.

Modern androgen therapy essentially began when testosterone was chemically synthesized in 1935. This scientific discovery (along with the discovery of other sex hormones - estrogen and progesterone) was awarded the Nobel Prize in Chemistry in 1939. Throughout most of its history, the concept of TD and replacement has been associated with confusion and controversy.

Concerns relating to prostate and cardiovascular health, performance enhancement via steroid abuse and the perception that TD is simply part of the “normal” process of aging has resulted in reluctance of many healthcare providers to diagnose and treat the condition.

In 2013, a comprehensive Canada-wide needs assessment revealed that over 25% of Canadian physicians were uncomfortable with the diagnosis and treatment of TD and identified significant knowledge gaps related to patient management.

To address the knowledge gaps, the Canadian Clinical Practice Guideline on the Diagnosis and Management of Testosterone Deficiency Syndrome in Adult Males was published in the CMAJ. As part of its mandate, the guideline was offered as a “living document,” to be updated periodically in a perpetual effort to incorporate advances in scientific and clinical discovery.

The current CUA guideline was approached in this spirit and serves as an educational tool that builds on existing knowledge and offers a contemporary update to the literature.

Grober ED, Krakowsky Y, Khera M, Holmes DT, Lee JC, Grantmyre JE, Patel P, Bebb RA, Fitzpatrick R, Campbell JD, Carrier S, Morgentaler A. Canadian Urological Association clinical practice guideline on testosterone deficiency in men: Evidence-based Q&A. Can Urol Assoc J. 2021 Feb 23. doi: 10.5489/cuaj.7252. Epub ahead of print. PMID: 33661092. Canadian Urological Association clinical practice guideline on testosterone deficiency in men: Evidence-based Q&A | Canadian Urological Association Journal

 

[Millard]

Hit the Gym, Skip the Testosterone for Healthy Vessels
— Exercise training is the winner for men in randomized trial

by Nicole Lou, Staff Writer, MedPage Today February 22, 2021

It was regular exercise, not a testosterone cream, that helped aging men in a randomized trial with their vascular endothelial function.

In men ages 50 to 70 with central adiposity and low-to-normal testosterone levels, flow-mediated dilation (FMD) actually declined with daily testosterone application, whereas it increased after 12 weeks of exercise training (P=0.033 overall) in the two-by-two factorial design comparison:

Testosterone plus exercise: FMD +0.5% from baseline
Placebo plus exercise: +1.0%
Testosterone plus no additional exercise: −0.7%
Placebo plus no additional exercise: +0.2%
FMD is a surrogate measure of the endothelial dysfunction implicated in atherosclerosis development.

Source: Hit the Gym, Skip the Testosterone for Healthy Vessels



Chasland LC, et al "Testosterone and exercise in middle-to-old aged men: combined and independent effects on vascular function" Hypertension 2021; https://doi.org/10.1161/HYPERTENSIONAHA.120.16411

 

[malfeasance]

Hit the Gym, Skip the Testosterone for Healthy Vessels
— Exercise training is the winner for men in randomized trial

by Nicole Lou, Staff Writer, MedPage Today February 22, 2021

It was regular exercise, not a testosterone cream, that helped aging men in a randomized trial with their vascular endothelial function.

In men ages 50 to 70 with central adiposity and low-to-normal testosterone levels, flow-mediated dilation (FMD) actually declined with daily testosterone application, whereas it increased after 12 weeks of exercise training (P=0.033 overall) in the two-by-two factorial design comparison:

Testosterone plus exercise: FMD +0.5% from baseline
Placebo plus exercise: +1.0%
Testosterone plus no additional exercise: −0.7%
Placebo plus no additional exercise: +0.2%
FMD is a surrogate measure of the endothelial dysfunction implicated in atherosclerosis development.

Source: Hit the Gym, Skip the Testosterone for Healthy Vessels

View attachment 144066

Chasland LC, et al "Testosterone and exercise in middle-to-old aged men: combined and independent effects on vascular function" Hypertension 2021; https://doi.org/10.1161/HYPERTENSIONAHA.120.16411

Very, very, very . . . very interesting.

They state it as "testosterone was not additive to exercise," but it actually looks like adding a small amount of testosterone harmed or decreased FMD compared to the exercise with no testosterone group.

Am I reading that result correctly?

 

[BBC3]

I've been away too long. And NOT to contradict any educated opinions and responses. I just caught the tail end of this..

I would only suggest as follows. and in my experience being a Gen X'r who started medicating TRT mid thirties...

1. It should be noted that Testosterone is a "Joker Card", in that when you add it, it will create androgens and estrogens in the same PROPORTIONS as which a person possesses either FAT or MUSCLE. Fat being a major estrogen generator. i HONESTLY DO NOT SEE HOW THEY CAN REFER TO TESTOSTERONE IN MEDICAL TERMS AS AN "ANDROGEN" WITH A STRAIGHT FACE.... The difference is CRITICAL and it should be noted the LAST article is clearly discussing old out of shape guys with pot bellies. The point is that clearly the VARIATION in Androgen OR Estrogen generation is night and day in the body. For all we know this whole concept could very well correlate with the relationship of Estrogen to blood clotting.. We however CAN NOT discount the VALUE of estrogen's role in normal male metabolism especially in terms of muscle building...

** I won't even go into my old hypothetical self as to PONDER how it might be possible that the best way to remove fat is to have that proper preponderance of estrogen metabolized, else we may become estrogen FAT locked should we deprive that already present body fat of fat enabling enzymatic potential and activity.. I DIGRESS... From the stars above...

2. I suspect this recently included article refers to creams and gels which are not comparable to injectable IM Depot. I could be wrong on my interpretation at just a quick glance. While I have read articles that indicate that sub-q test injections for TRT are androgen productive. I DO NOT believe the study criteria was properly conducted. I believe the age-old bro science is correct in the EXPERIENCE that Testosterone implanted in fat makes more Estrogen as opposed to IM application. Overall...

3. TIME is of the essence. And the rules change as one grows not just "older", but more "Couch wasted"... We are talking about the potential validation of "life extension" and "health and wellness" protocols. But only when mitigated in time. AGE/experience/CONDITION IS THE FACTOR...

4. This does not mean that people can not benefit from TRT. However, it may indicate, that providing TRT to sedentary males who are already couch-wasted AND who do NOT endeavor a physical training regimen concomitantly, could POSSIBLY be making matters worse... Testosterone application in terms of physical fitness and conditions is a catch-22 teeter-totter which once one gets laden to the out of shape fat side is almost non-recoverable. And even for previously trained athletes. As for those guys that never did squat when they were younger CAN FORGET IT... But hey, we are in a "Kill'em off world" RIGHT??? So much and the COST DOES NOT OUTWEIGHT THE BENEFIT.. L......O.......L......

*** you really got to back up on that PUN and just bow down.. LOL

5. I have NEVER GAINED a nickel of STRENGTH or ERECTILE CAPACITY from TRT alone. I have however noted a strong correlation with a counter-action to the normal wear and tear of physically sedentary lifestyle. At the early enough age where some level of fitness remains. In short I could quit working out for long periods of time while on TRT and have muscle mass remain in place. BUT, if I ever quite BOTH TRT and exercise at the same time, I turned into a steaming pile of shit almost overnight.

6. Exogenous IM testosterone application has, however, ALWAYS produced an increase in protein synthesis thus transferred to faster healing and a quicker metabolism. Even if ever so slightly in my worst of worst physical conditions. It still just about HALTS muscle degradation, wasting, and general time pertaining atrophy in it's trax...

7. The problem again is how far gone are you. I will only add that in my recent return to training near 50, I WAS DUMBFOUNDED as to how "impossible" it seemed to recover my physical condition. And we are talking joint and connective tissue aside from this discussion (that was a whole nother complication).. But I am here to tell you when one attempts to improve their life with TRT, they should be prepared for a ride proportionate to their current level of fitness, and with consideration to how far out from their max potential they have strayed.

In short, if you let yourself go to the point that you are not even in youthful high school levels of strength training. The returns from T administration will be be close to non-existent.

Translated to CLASSIC Bro-Speak... "If you are fat, testosterone will not do much for you"... (wise words from the experienced old schoolerz)

In my older more experienced age my advice at guys around 50 attempting to get in shape would be DONT EVEN THINK ABOUT running testosterone (or any steroid) in high doses for that matter. It's a big "wheel-spin" to nowhere by side-effects - AKA - Unwanted effects. And with the DESIRED EFFECT SEEMINGLING ELUDING YOU LEAVING YOU IN A TWILIGHT ZONE AS 2+2 NO LONGER EQUALS FOUR..!!! I'll leave this calculation somewhat ambiguous.

I will confess, and its been so long since I have participated here, that at this point in this POST - I did go back and review the first 4 pages of the thread. Just to make sure I was not talking TOTALLY out of my ass. At the same time I did not want to spoil my harvest of personal experience pertaining to OLD ME vs. NEW ME.. It was a unique experiment to witness first hand how my perceptions and position compares currently NOW vs. THEN... I was actually surprised in that I did not recall my participation in this thread prior. Lol just fuk....

I feel fairly confident that my general position in prior writing is similar, whatever..., now holding an additional wealth of experience - I add the following... THE ISSUE with old guys is TWO FOLD...:
1. (The big one and pertaining to body fat composition)... We have run our IGF-1 in the dirt thru dietary abuse and thus resulting CAN NO longer get a proper insulin kick from food. In short Type 2 diabetes holds a much larger implication that can be understood. It also brings up an interesting topic as to the actual real value of instant release insulin vs. long acting. NO I am not diabetic yet nor have I ever supplemented insulin.
2. Most importantly our 50 yr old bodies have throttled back GH metabolism for a reason... We miss our window to train for mass if not done before 25 or so. And IT SURELY REPORTS when we are 50... But if it did not throttle down, we would all look like that Skinimaz star villain from 1990's......


That guy's name is Robert Z'dar from Chicago BTW and he ROCCKED. He died sometime around an actors deal that occurs once a year in Pensacola and sometime around 2015. He was a most supreme screen-face..

While in my mid 30's, supplementing testosterone provided the kick I needed for youth-like healing and thus a direct return in strength increase. At 50, not so much. However it does keep me from going straight in the ground and give me a fighting chance...

I used to banter on about "what we needed was a STRICT ANDROGEN REPLACEMENT in order to avoid the estrogen side-effects". And THAT IS the THREAD TITLE after all... Right..??? I never knew there was a drug called PROVIRON that is NOT prescribed in the US which appears to be an Androgen derivative that skips the potential conversion to Estrogen... Perhaps I missed a note or advisory. A lot of folks even make claims that it restores normal erectile capacity in aging men within a couple of months of medical grade dosing. I have since tried it at one time or another and it completely freaked me out as even at 25mgs the stuff completely blew my doors off with Blood pressure increase to the point that I swear they sent me mislabeled Anadrol. It is possible and considering my source. Medically in the UK, I think they dose the stuff on top of 50-150mgs TRT per/day... I recently read a thread somewhere in which a guy is swearing he got a stronger (nastier) response from a lower dose. I kinda believe it. Else he got the same mismarked shit I did...

I'm done fer now...

 

[Cashton]

I've been away too long. And NOT to contradict any educated opinions and responses. I just caught the tail end of this..

I would only suggest as follows. and in my experience being a Gen X'r who started medicating TRT mid thirties...

1. It should be noted that Testosterone is a "Joker Card", in that when you add it, it will create androgens and estrogens in the same PROPORTIONS as which a person possesses either FAT or MUSCLE. Fat being a major estrogen generator. i HONESTLY DO NOT SEE HOW THEY CAN REFER TO TESTOSTERONE IN MEDICAL TERMS AS AN "ANDROGEN" WITH A STRAIGHT FACE.... The difference is CRITICAL and it should be noted the LAST article is clearly discussing old out of shape guys with pot bellies. The point is that clearly the VARIATION in Androgen OR Estrogen generation is night and day in the body. For all we know this whole concept could very well correlate with the relationship of Estrogen to blood clotting.. We however CAN NOT discount the VALUE of estrogen's role in normal male metabolism especially in terms of muscle building...

** I won't even go into my old hypothetical self as to PONDER how it might be possible that the best way to remove fat is to have that proper preponderance of estrogen metabolized, else we may become estrogen FAT locked should we deprive that already present body fat of fat enabling enzymatic potential and activity.. I DIGRESS... From the stars above...

2. I suspect this recently included article refers to creams and gels which are not comparable to injectable IM Depot. I could be wrong on my interpretation at just a quick glance. While I have read articles that indicate that sub-q test injections for TRT are androgen productive. I DO NOT believe the study criteria was properly conducted. I believe the age-old bro science is correct in the EXPERIENCE that Testosterone implanted in fat makes more Estrogen as opposed to IM application. Overall...

3. TIME is of the essence. And the rules change as one grows not just "older", but more "Couch wasted"... We are talking about the potential validation of "life extension" and "health and wellness" protocols. But only when mitigated in time. AGE/experience/CONDITION IS THE FACTOR...

4. This does not mean that people can not benefit from TRT. However, it may indicate, that providing TRT to sedentary males who are already couch-wasted AND who do NOT endeavor a physical training regimen concomitantly, could POSSIBLY be making matters worse... Testosterone application in terms of physical fitness and conditions is a catch-22 teeter-totter which once one gets laden to the out of shape fat side is almost non-recoverable. And even for previously trained athletes. As for those guys that never did squat when they were younger CAN FORGET IT... But hey, we are in a "Kill'em off world" RIGHT??? So much and the COST DOES NOT OUTWEIGHT THE BENEFIT.. L......O.......L......

*** you really got to back up on that PUN and just bow down.. LOL

5. I have NEVER GAINED a nickel of STRENGTH or ERECTILE CAPACITY from TRT alone. I have however noted a strong correlation with a counter-action to the normal wear and tear of physically sedentary lifestyle. At the early enough age where some level of fitness remains. In short I could quit working out for long periods of time while on TRT and have muscle mass remain in place. BUT, if I ever quite BOTH TRT and exercise at the same time, I turned into a steaming pile of shit almost overnight.

6. Exogenous IM testosterone application has, however, ALWAYS produced an increase in protein synthesis thus transferred to faster healing and a quicker metabolism. Even if ever so slightly in my worst of worst physical conditions. It still just about HALTS muscle degradation, wasting, and general time pertaining atrophy in it's trax...

7. The problem again is how far gone are you. I will only add that in my recent return to training near 50, I WAS DUMBFOUNDED as to how "impossible" it seemed to recover my physical condition. And we are talking joint and connective tissue aside from this discussion (that was a whole nother complication).. But I am here to tell you when one attempts to improve their life with TRT, they should be prepared for a ride proportionate to their current level of fitness, and with consideration to how far out from their max potential they have strayed.

In short, if you let yourself go to the point that you are not even in youthful high school levels of strength training. The returns from T administration will be be close to non-existent.

Translated to CLASSIC Bro-Speak... "If you are fat, testosterone will not do much for you"... (wise words from the experienced old schoolerz)

In my older more experienced age my advice at guys around 50 attempting to get in shape would be DONT EVEN THINK ABOUT running testosterone (or any steroid) in high doses for that matter. It's a big "wheel-spin" to nowhere by side-effects - AKA - Unwanted effects. And with the DESIRED EFFECT SEEMINGLING ELUDING YOU LEAVING YOU IN A TWILIGHT ZONE AS 2+2 NO LONGER EQUALS FOUR..!!! I'll leave this calculation somewhat ambiguous.

I will confess, and its been so long since I have participated here, that at this point in this POST - I did go back and review the first 4 pages of the thread. Just to make sure I was not talking TOTALLY out of my ass. At the same time I did not want to spoil my harvest of personal experience pertaining to OLD ME vs. NEW ME.. It was a unique experiment to witness first hand how my perceptions and position compares currently NOW vs. THEN... I was actually surprised in that I did not recall my participation in this thread prior. Lol just fuk....

I feel fairly confident that my general position in prior writing is similar, whatever..., now holding an additional wealth of experience - I add the following... THE ISSUE with old guys is TWO FOLD...:
1. (The big one and pertaining to body fat composition)... We have run our IGF-1 in the dirt thru dietary abuse and thus resulting CAN NO longer get a proper insulin kick from food. In short Type 2 diabetes holds a much larger implication that can be understood. It also brings up an interesting topic as to the actual real value of instant release insulin vs. long acting. NO I am not diabetic yet nor have I ever supplemented insulin.
2. Most importantly our 50 yr old bodies have throttled back GH metabolism for a reason... We miss our window to train for mass if not done before 25 or so. And IT SURELY REPORTS when we are 50... But if it did not throttle down, we would all look like that Skinimaz star villain from 1990's......
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That guy's name is Robert Z'dar from Chicago BTW and he ROCCKED. He died sometime around an actors deal that occurs once a year in Pensacola and sometime around 2015. He was a most supreme screen-face..

While in my mid 30's, supplementing testosterone provided the kick I needed for youth-like healing and thus a direct return in strength increase. At 50, not so much. However it does keep me from going straight in the ground and give me a fighting chance...

I used to banter on about "what we needed was a STRICT ANDROGEN REPLACEMENT in order to avoid the estrogen side-effects". And THAT IS the THREAD TITLE after all... Right..??? I never knew there was a drug called PROVIRON that is NOT prescribed in the US which appears to be an Androgen derivative that skips the potential conversion to Estrogen... Perhaps I missed a note or advisory. A lot of folks even make claims that it restores normal erectile capacity in aging men within a couple of months of medical grade dosing. I have since tried it at one time or another and it completely freaked me out as even at 25mgs the stuff completely blew my doors off with Blood pressure increase to the point that I swear they sent me mislabeled Anadrol. It is possible and considering my source. Medically in the UK, I think they dose the stuff on top of 50-150mgs TRT per/day... I recently read a thread somewhere in which a guy is swearing he got a stronger (nastier) response from a lower dose. I kinda believe it. Else he got the same mismarked shit I did...

I'm done fer now...

That was a whole lot to process man…

 

[BBC3]

That was a whole lot to process man…

Yea, I'm kinda crazy like that.... LOL

 

[pierrebobin]

I juts read the whole post, want to share a few things.
Huge thanks to Michael Scally for his contribution, however :
- i noticed the bad things with T are in red
- i noticed the good things with T are not
why?

 

[BBC3]

I juts read the whole post, want to share a few things.
Huge thanks to Michael Scally for his contribution, however :
- i noticed the bad things with T are in red
- i noticed the good things with T are not
why?

If you were referring to my post. Congratulations, you must take adderall too. You are one of the few to make the journey. LOL

FYI I used to use BLUE to ameliorate and highlight the potential positives. I just decided at some point that I was being to FLASHY.. LOL