AAS – CNS Effects

[Michael Scally MD]

[OA] Androgen Misuse and Abuse

Androgens are potent drugs requiring prescription for valid medical indications but are misused for invalid, unproven, or off-label reasons as well as being abused without prescription for illicit non-medical application for performance or image enhancement. Following discovery and first clinical application of testosterone in the 1930s, commercialisation of testosterone and synthetic androgens proliferated in the decades after World War II.

It remains among the oldest marketed drugs in therapeutic use, yet after 8 decades of clinical use the sole unequivocal indication for testosterone remains in replacement therapy for pathological hypogonadism, organic disorders of the male reproductive system. Nevertheless, wider claims assert unproven, unsafe, or implausible benefits for testosterone, mostly representing wishful thinking about rejuvenation.

Over recent decades this created an epidemic of testosterone misuse involving prescription as a revitalizing tonic for anti-ageing, sexual dysfunction and/or obesity, where efficacy and safety remains unproven and doubtful. Androgen abuse originated during the Cold War as an epidemic of androgen doping among elite athletes for performance enhancement before the 1980s when it crossed over into the general community to become an endemic variant of drug abuse in sufficiently affluent communities that support an illicit drug industry geared to bodybuilding and aiming to create a hypermasculine body physique and image.

This review focuses on the misuse of testosterone, defined as prescribing without valid clinical indications, and abuse of testosterone or synthetic androgens (androgen abuse), defined as the illicit use of androgens without prescription or valid indications, typically by athletes, body-builders and others for image-oriented, cosmetic or occupational reasons.

Handelsman DJ. Androgen Misuse and Abuse. Endocr Rev. 2021 Jan 23:bnab001. doi: 10.1210/endrev/bnab001. Epub ahead of print. PMID: 33484556. https://academic.oup.com/edrv/advance-article/doi/10.1210/endrev/bnab001/6117781

 

[Michael Scally MD]

[OA] Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review

Anabolic-androgenic steroids (AASs) are a large group of molecules including endogenously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes' performance, minimizing androgenic effects.

AAS use is very popular and 1-3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue.

The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs.

Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field.

In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation.

Albano GD, Amico F, Cocimano G, Liberto A, Maglietta F, Esposito M, Rosi GL, Di Nunno N, Salerno M, Montana A. Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review. Healthcare (Basel). 2021 Jan 19;9(1):E97. doi: 10.3390/healthcare9010097. PMID: 33477800. https://www.mdpi.com/2227-9032/9/1/97/htm

 

[Michael Scally MD]

Anabolic Steroid Use and Ischaemic Stroke in A Young Fitness Enthusiast

We report a case of ischaemic stroke in a 34-year-old male recreational bodybuilder following a 3-month period of anabolic androgenic steroid (AAS) use and 1-month period of 'post-cycle therapy' (tamoxifen and clomiphene citrate), the latter treatments aimed at restoring normal endogenous testosterone production after initial AAS use.

We hypothesise a transient drug-related prothrombotic state with paradoxical embolisation via an atrial septal defect which was later found on bubble echocardiogram.

We highlight a rare but important cause of stroke in younger patients which is relevant given the increasing use of AAS misuse among casual fitness enthusiasts.

We explore the various possible mechanisms by which AAS use can increase ischaemic stroke risk in such patients.

Choulerton J, Guha N, Squires R. Anabolic steroid use and ischaemic stroke in a young fitness enthusiast. BMJ Case Rep. 2021 Feb 4;14(2):e234241. doi: 10.1136/bcr-2020-234241. PMID: 33542023. Anabolic steroid use and ischaemic stroke in a young fitness enthusiast | BMJ Case Reports

 

[Michael Scally MD]

[OA] Testosterone Use and Abuse : Methodological Aspects in Forensic Toxicology and Clinical Diagnostics

Abuse of anabolic androgenic steroids (AAS) is widespread in society and is today a major public health problem, associated with mental and somatic adverse effects and risk behavior, such as use of other illicit drugs and criminality. Testosterone, the most important endogenous male androgen, is therapeutically used in replacement therapy but is also extensively used as a doping agent.

Traditionally, testosterone abuse is detected in urine in forensic cases and in serum in clinical diagnosis and monitoring, and free bioavailable serum testosterone is calculated by formulas. Salivary testosterone is however an attractive biomarker, as testosterone in saliva is supposed to reflect free testosterone in serum.

The aim of this thesis was to investigate the abuse of AAS from a forensic perspective, particularly focusing on testosterone and methodological problems and potential alternative matrices for measurements of testosterone in forensic and clinical assessments.

In the first study the toxicological findings in individuals suspected of doping offences, registered in the Swedish national forensic toxicology database were investigated (paper I). In paper II, testosterone levels in serum, saliva, and urine in clinical patients during replacement therapy with testosterone undecanoate (Nebido®) were studied.

Further, the sensitivity of the current procedure for detection of testosterone abuse was investigated by method comparison using isotope ratio measurement (paper III) and a quantitative LC-MS/MS method for testosterone in serum and saliva was developed and presented (paper IV).

It was found that testosterone was most frequently detected in the forensic cases and co-abuse of narcotics was common among AAS abusers. Methodological problems in detection of testosterone abuse using the present procedures was identified, indicating a need for new analytical strategies. A sensitive and highly specific LC-MS/MS method was developed for determination of testosterone in serum and saliva, which was shown suitable for analysis of forensic and clinical samples.

Salivary testosterone was shown to correlate well with free serum testosterone in both male and female, and a sensitive marker in testosterone therapy, especially in females. In conclusion, it was found that saliva might have a potential as an alternative matrix for detection of illicit administration of testosterone and for diagnosis and monitoring of androgenic status.

Lood, Y. (2021). Testosterone Use and Abuse : Methodological Aspects in Forensic Toxicology and Clinical Diagnostics (PhD dissertation). Linköping University Electronic Press, Linköping. Testosterone Use and Abuse: Methodological Aspects in Forensic Toxicology and Clinical Diagnostics / Testosterone Use and Abuse: Methodological Aspects in Forensic Toxicology and Clinical Diagnostics

 

[Michael Scally MD]

Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes
Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes - Full Text View - ClinicalTrials.gov

This study evaluates the association between testosterone levels and risk of dementia and adverse mental health outcomes (e.g. depression and anxiety).

It is not known whether low testosterone levels may be associated with an increased risk of dementia.

Learning about the association between testosterone levels and risk of dementia may help determine the long-term effects of androgen deprivation therapy and may help improve quality of life.

 

[Old]

"Deviant brain aging". That's the first time I've heard the term. Is it some fancy new medical condition created for steroid users?

Perhaps its just language difference as this study was European. Nevertheless, deviant simply means 'different than the norm'. So, with AAS users, they have deviant muscles so why not deviant brains, lol. Now in this country that word is that is the crux of discrimination ... AAS users are a minority, thus different, thus something must be wrong with them (and with some there IS something wrong as there is with the general population too).

Results AAS users had higher BAG compared to weightlifting controls, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure.

Conclusions The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AAS.

This is kind of a no-brainer [pun intended]. Biological processes produce metabolic waste. Increasing T increases biological processes, thus waste. If the increase exceeds the body's ability to remove/process the waste, then oxidative damage occures.

This highlights why it is important for an athlete, AAS user or not, to live a lifestyle that maximized the body's ability to repair (diet, sleep, etc.). This point is a bone of contention older bodybuilders have about most of the younger generation using AAS - their lifestyle is asking for trouble and not compatible with 'safe' use of steroids. Not only will they suffer but the whole community will as many crash prompting governments to intervene and 'rescue' these 'deviants' from themselves.

So... AAS accelerate free radical formation thus potentially "accelerated brain aging" as seen in this study. It would be interesting to see what levels constituded "no evidence of increased brain aging in the overall AAS group" verses "longer AAS exposure". What is the distinction between 'overall' and 'longer'? If overall mean's all, then some had decreased brain aging to compensate for the accelerated ones and bring the average to 'no evidence'.

As for "potentially linked to dependency and exaggerated use of AAS" this is more double talk. How does one link dependency to brain-aging when the brain-aging has to come first to cause the dependency? Perhaps I misunderstand the authors - better wording is needed if that is so.

 

[Michael Scally MD]

[OA] [GMAFB] Anabolic Androgenic Steroids, Antisocial Personality Traits, Aggression and Violence

Highlights

Aggression and violence is associated with steroid use, particularly steroid dependence.

The link between steroid use and aggression and violence is complex.

Antisocial personality traits seem to be involved in the link between steroid use and violence.

Background: Anabolic androgenic steroid (AAS) use is associated with a wide range of adverse physical, psychological and social effects. While some experience few side effects, others might experience severe consequences.

Aggression and violence are among the often-cited side effects associated with high-dose AAS use; however, most of the knowledge is generated from subgroups, such as prison populations.

A likely hypothesis is that AAS use is associated with aggression and violence, but that these associations are complex and may be mediated by several factors, such as substance use, AAS dependence and personality traits.

Methods: In the present study, we tested this hypothesis by examining the relations between long-term AAS use and AAS dependence, aggression, interpersonal violence and potential mediating factors in a sample of male AAS exposed and non-exposed weightlifting controls (WLC), using self-report questionnaires. Based upon AAS dependence criteria, a sample of male AAS users and WLC (N = 139) were stratified into three groups: WLC (n = 66), AAS dependents (n = 41) and AAS non-dependents (n = 32).

Results: The results demonstrate that AAS dependents reported significantly higher levels of aggression compared to WLC and AAS non-dependents. While interpersonal violence was reported in all three groups, the highest percentage was found in the AAS dependent group.

Conclusion: In summary, our study confirms a link between AAS use, aggression and violence in a weightlifting population. However, the association is foremost seen in AAS dependent users and it seems that antisocial personality traits are an important mediator.

[OA] Hauger LE, Havnes IA, Jørstad ML, Bjørnebekk A. Anabolic androgenic steroids, antisocial personality traits, aggression and violence. Drug Alcohol Depend. 2021 Feb 17;221:108604. doi: 10.1016/j.drugalcdep.2021.108604. Epub ahead of print. PMID: 33621808. Anabolic androgenic steroids, antisocial personality traits, aggression and violence

 

[Millard]

Long-Term Anabolic Androgenic Steroid Use Is Associated with Deviant Brain Aging

Background High-dose long-term use of anabolic-androgenic steroids (AAS) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging.

Methods T1-weighted MRI (3D MPRAGE) scans were obtained from male weightlifters with a history of prolonged (n=130) or no (n=99) AAS use. We trained machine learning models on combinations of regional brain volumes, cortical thickness and surface area in an independent training set of 1838 healthy males (18-92 years) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval 3.5 years, n=76) MRI data, we used linear mixed effects (LME) models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration and dependence.

Results AAS users had higher BAG compared to weightlifting controls, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure.

Conclusions The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AAS.

Bjørnebekk A, Kaufmann T, Hauger LE, Klonteig S, Hullstein IR, Westlye LT. Long-term anabolic androgenic steroid use is associated with deviant brain aging. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2021. http://www.sciencedirect.com/science/article/pii/S2451902221000197

If overall mean's all, then some had decreased brain aging to compensate for the accelerated ones and bring the average to 'no evidence'.

As for "potentially linked to dependency and exaggerated use of AAS" this is more double talk. How does one link dependency to brain-aging when the brain-aging has to come first to cause the dependency? Perhaps I misunderstand the authors - better wording is needed if that is so.

Some important notes upon reading details:

There was NO SIGNIFICANT DIFFERENCE in "deviant brain aging" in these two groups when compared to non-AAS users:

1) Previous AAS users (those who discontinued more than 6 months ago)

2) Non-dependent AAS users (those who did not meet research criteria for dependence)

So, the "aging" goes away (transient) after AAS are stopped.

And only certain AAS users - who meet specific psychological criteria - show signs of "aging"

This seems important to me.

 

[skinnyman]

Does testosterone base affect the CNS?

Feels like it fires up the CNS within 30-60min after taking it and feel it from time to time couple of hours after injection.

Feels like drinking a lot of coffee after having a long caffeine break.

 

[TomGlass]

I've used the search and can't find information about this anywhere on here and I think this would be the best thread to ask this. I am new to aas, this is my first cycle of 500test 700npp with aromasin on hand.
Whenever I start feeling lethargic and wanting to nap all day I'll take 12.5mg aromasin. I'll wait 2 days to see if symptoms improve then maybe take another 12.5mg. I get from research a single dose of aromasin reaches its peak effectiveness at about 2-3 days and can last up to 5.

I'm in my 4th week of test500 and just finished my first week of 700npp. My question has to deal with short-term memory. I would put something down and completely blank of where i put it. Even after finding it i still won't remember putting it there. Ive done this with my keys, pills, earbuds, whatever. I started noticing this at the end of my 3rd week.
Has anyone noticed this before? I've read there is a correlation between estradiol and spatial, social, and object recognition memory.

I know it's frowned upon but if I'm going by feels can I take this as a sign that my e2 is too low? Other than lethargy and water retention or at the other end of the spectrum, being unusually forgetful, I don't notice any other sides.

 

[AnabolicBill]

a very long but interesting read, thank you for posting this up bro.

 

[AlexDavis43]

I know it's frowned upon but if I'm going by feels can I take this as a sign that my e2 is too low? Other than lethargy and water retention or at the other end of the spectrum, being unusually forgetful, I don't notice any other sides.

This kind of feelz report is fine imo but if this is consistent, consult doc.

Hopefully it's easily corrected with drugs.

 

[lukiss96]

I've used the search and can't find information about this anywhere on here and I think this would be the best thread to ask this. I am new to aas, this is my first cycle of 500test 700npp with aromasin on hand.
Whenever I start feeling lethargic and wanting to nap all day I'll take 12.5mg aromasin. I'll wait 2 days to see if symptoms improve then maybe take another 12.5mg. I get from research a single dose of aromasin reaches its peak effectiveness at about 2-3 days and can last up to 5.

I'm in my 4th week of test500 and just finished my first week of 700npp. My question has to deal with short-term memory. I would put something down and completely blank of where i put it. Even after finding it i still won't remember putting it there. Ive done this with my keys, pills, earbuds, whatever. I started noticing this at the end of my 3rd week.
Has anyone noticed this before? I've read there is a correlation between estradiol and spatial, social, and object recognition memory.

I know it's frowned upon but if I'm going by feels can I take this as a sign that my e2 is too low? Other than lethargy and water retention or at the other end of the spectrum, being unusually forgetful, I don't notice any other sides.

Your first cycle is very reckless. You could have achieved the same with much less and Testosterone only. Now you don't know what is causing what and playing with meds by feels. That's what you get when you start playing with 19 nors on your first time.

No blood work, how can we tell if your e2 is too high? Besides that npp/deca are known to make it harder to manage estrogen.

You just shot yourself in the foot wanting fast gains. Hell, it could be worse, be thankful that you're not developing gyno or something.

We say it for a reason - learn your body first, see how you react to steroids one by one.

Next time be smarter about it and monitor your parameters, you're playing a guessing game and hoping for the best.

Do more research and post a thread asking for help if you're not sure about something, it's better to ask 5 times to be safe, than be sorry later on.

I advise you to seek advice before doing something, not in the middle of problems where you are desperate and need quick help. Will save you time and trouble. Don't play with fire when it comes to steroids and drugs. Stay safe.

 

[TomGlass]

Your first cycle is very reckless. You could have achieved the same with much less and Testosterone only. Now you don't know what is causing what and playing with meds by feels. That's what you get when you start playing with 19 nors on your first time.

No blood work, how can we tell if your e2 is too high? Besides that npp/deca are known to make it harder to manage estrogen.

I appreciate your input. Although i made it sound like I just jumped right into aas without knowing how to swim, I will say that aas is something I've been thinking about for a few years and have done a lot of reading. Not that any of this will change your opinion and I agree to a certain extent, that being bloods are ideal, but I wouldn't say I'm reckless. I know my e2 is high when the lethargy starts then the acne flairs, that's how I know. My diet and sleep has been on point for some time now so the only contributing factor would be what I am taking. The 12.5mg aromasin every 3-4 days relieves these symptoms.

 

[DugPrime]

Anabolic Steroids Alter the Physiological Activity of Aggression Circuits in the Lateral Anterior Hypothalamus [Blah Blah Blah]

Highlights
· Adolescent AAS exposure alters neuronal firing parameters in the hypothalamus.
· LAH neuronal activity and aggressive behavior are correlated in AAS animals.
· AAS increases the proportion of responsive cells that are excited by AVP.
· AAS lowers the proportion of cells that respond to DA D2 receptor antagonists.

Morrison TR, Sikes RW, Melloni RH, Jr. Anabolic Steroids Alter the Physiological Activity of Aggression Circuits in the Lateral Anterior Hypothalamus. Neuroscience. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus

Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies.

Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations.

For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression.

To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior.

The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular).

AAS treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP.

Both DA D2 antagonists and 5HT increased the firing frequency of AVP responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone.

These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding.

More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.

I know that message was almost 10 years ago, but, to counteract vasopressin-related water retention, aggression and insomnia, targeting both V1 and V2 receptors with an antagonist like tolvaptan could potentially help?