AAS – CNS Effects

[Michael Scally MD]

[RUFKM] Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

Modulation of tryptophan (Trp) metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS) and associated image and performance enhancers.

Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO) inhibition and enhancement of serotonin function.

Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines.

Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes.

Badawy AA. Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents. International journal of tryptophan research: IJTR 2018;11:1178646917753422. Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

 

[Michael Scally MD]

Associations of Anabolic-Androgenic Steroid Use with Other Behavioral Disorders: An Analysis Using Directed Acyclic Graphs

BACKGROUND: Anabolic-androgenic steroid (AAS) use is known to be associated with other psychiatric disorders, such as body image disorders, conduct disorder/sociopathy, and other substance use disorders (SUD) - but the causal pathways among these conditions remain poorly delineated.

METHODS: We created a directed acyclic graph to diagram hypothesized relationships among AAS use and dependence, body image disorder (BID), conduct disorder/sociopathy, and other SUD. Using proportional hazards models, we then assessed potentially causal relationships among these variables, using a dataset of 233 male weightlifters, of whom 102 had used AAS.

RESULTS: BID and conduct disorder/sociopathy both strongly contributed to the development of AAS use, but did not appear to contribute further to the progression from AAS use to AAS dependence. Other SUD beginning prior to first AAS use - whether broadly defined or restricted only to opioids - failed to show an effect on AAS use or progression to AAS dependence.

Conversely, AAS use contributed significantly to the subsequent first-time development of opioid use disorders but did not significantly increase the risk for first-time development of non-opioid SUD, taken as a whole.

CONCLUSIONS: Our analysis suggests that AAS use and other SUD are mutually attributable to underlying conduct disorder/sociopathy. SUD do not appear to represent a 'gateway' to subsequent AAS use. AAS use may represent a gateway to subsequent opioid use disorder, but probably not to other SUD.

Kanayama G, Pope HG, Hudson JI. Associations of anabolic-androgenic steroid use with other behavioral disorders: an analysis using directed acyclic graphs. Psychological medicine 2018:1-8. Associations of anabolic-androgenic steroid use with other behavioral disorders: an analysis using directed acyclic graphs. - PubMed - NCBI

 

[Michael Scally MD]

[OA] Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication.

We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal.

This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control.

The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

Hildebrandt T, Heywood A, Wesley D, Schulz K. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal. Front Psychol 2018;9:390. https://www.frontiersin.org/articles/10.3389/fpsyg.2018.00390/full

 

[Michael Scally MD]

[OA] Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

Since its discovery, several chemical modifications in the testosterone molecule have been done by pharmaceutical industry in order to improve its pharmacological effects, resulting in the creation of anabolic steroids (AS).

Despite the therapeutic benefits, AS abuse has spread among elite and recreational athletes in the search for improvements on physical appearance and physical performance. Illicit use of anabolic AS has been correlated with several adverse effects, such as cardiovascular, endocrine, reproductive and neurobehavioral dysfunctions.

Recently, declines on cognitive and mnemonic performance have been demonstrated clinically and experimentally. Experimental studies have demonstrated that these neurological dysfunctions are correlated to spread neuronal apoptosis throughout important areas of the central nervous system (CNS), such as hippocampus and cortex. Several pathophysiological mechanisms have been linked to the AS-induced neurotoxicity, including redox imbalance and recruitment of pro-apoptotic downstream pathways.

Furthermore, exposure to AS has arisen as a potential risk factor to the development of Alzheimer’s disease. Altogether, these evidences imply that AS abuse per se induces neurodegeneration and can aggravate the prognosis of neurodegenerative diseases.

Fernando de Azevedo Cruz Seara, Rodrigo Soares Fortunato, Denise Pires Carvalho, José Hamilton Matheus Nascimento. Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders. In Sex Hormones in Neurodegenerative Processes and Diseases, 2018. Neurophysiological Repercussions of... (PDF Download Available)

 

[Michael Scally MD]

[OA] [GMAFB] Behavioral Alterations of Supraphysiological Doses of Androgenic Anabolic Steroids

Literature data offers evidence that AASs abuse is accompanied with psychiatric manifestations, as well as with different behavioral alterations from mild type, which are social acceptable, to uncontrolled and impulsive behavior with expression of aggression, anxiety, hypomania, and also manic episodes. Numerous investigations were performed on animal experimental models in order to make an insight to mechanisms underlying mechanisms for AASs impact on behavioral alterations.

The absolute majority of literature sources declared the anxiogenic effect of AASs when applied in supraphysiological doses. The increased anxiety levels following AASs treatment seems to be a consequence of changes in various neuroregulatory systems (gabaergic, dopaminergic, etc.), as well as alterations in sex hormones receptors in specific brain regions, including hippocampus.

Supraphysiological doses of AASs also affect mood by means of increased depressiveness. The prodepressant action of AASs is usually accompanied with significant reduction of growth factors (NGF, BDNF) release with consequent effects on neuromodulatory systems (gabaergic, dopaminergic) in rat prefrontal cortex and hippocampus.

When applied in supraphysiological dose AAS significantly affected the quality of cognitive abilities, manifested as significant decline in spatial learning and memory. The negative impact of AASs on cognitive functions was attributed to significant alterations in acetylcholine, dopamine, norepinephrine, glutamate and serotonin levels in specific brain regions, responsible for regulation of learning and memory.

Dragica S, Jovana J, Gvozden R. Behavioral Alterations of Supraphysiological Doses of Androgenic Anabolic Steroids - A mini review. Proceedings of the Nature Research Society 2018;2:02007. http://dx.doi.org/10.11605/j.pnrs.201802007

 

[Michael Scally MD]

Adverse Effects, Health Service Engagement, and Service Satisfaction Among Anabolic Androgenic Steroid Users

There are a number of adverse health effects associated with the use of anabolic androgenic steroids (AAS), ranging from mood disturbances to gynecomastia and impaired sexual function. Despite the potentially serious nature of adverse effects, evidence suggests that users are reluctant to seek medical assistance.

This study explores factors associated with health service engagement and treatments related to service satisfaction among a sample of AAS users. The analyses are based on a sample of 195 respondents from the Global Drug Survey 2015 who reported using steroids in the previous 12-month period and experiencing concerns about adverse health effects.

The results indicate reluctance among AAS users to engage with health services, with only 35.23% reporting that they visited a doctor when experiencing concerns about adverse effects. Concern about sexual function increased the likelihood that users engaged with health services, while concern about changes in sexual organs decreased the odds of service engagement.

Among AAS users who engaged with health services, individuals who received a mental health assessment or diabetes test rated the service as more helpful than those who did not; a finding that resonates with literature indicating a desire among AAS users to monitor the health impacts of their drug use and respond to issues as they arise.

WHILE MORE RESEARCH IS NEEDED, THE PRESENT RESULTS UNDERSCORE A NEED FOR NONJUDGMENTAL HEALTH SERVICES AIMED AT ASSISTING AAS USERS TO MONITOR ADVERSE EFFECTS AND MINIMIZE HARM THROUGH EARLY INTERVENTION.

Zahnow R, McVeigh J, Ferris J, Winstock A. Adverse Effects, Health Service Engagement, and Service Satisfaction Among Anabolic Androgenic Steroid Users. Contemporary Drug Problems 2017;44:69-83. SAGE Journals: Your gateway to world-class journal research

 

[Michael Scally MD]

[OA] [GMAFB] Anabolic Steroid-induced Mania

There are numerous reports of the psychiatric effects of anabolic-androgenic steroid (AAS) use. However, these effects have not been clearly elicited in controlled clinical trials. This discrepancy is largely due to the presence of a variety of synergistic factors seen in the real-life setting of AAS abuse.

In this case, we report a patient in acute mania admitted to Frederick Memorial Hospital in Frederick, Maryland. He had no prior history or family history of manic episodes. His symptoms were refractory to initial pharmacologic intervention.

The onset of his symptoms was likely related to the initiation of AAS use. However, his symptoms were likely potentiated by heavy daily cannabis use.

The patient showed a gradual improvement over the second week of his hospitalization. He was discharged on antipsychotics and scheduled to follow up with a therapist and psychiatrist.

Franey DG, Espiridion ED. Anabolic Steroid-induced Mania. Cureus 2018;10:e3163. Anabolic Steroid-induced Mania

 

[CensoredBoardsSuck]

[OA] [GMAFB] Anabolic Steroid-induced Mania

There are numerous reports of the psychiatric effects of anabolic-androgenic steroid (AAS) use. However, these effects have not been clearly elicited in controlled clinical trials. This discrepancy is largely due to the presence of a variety of synergistic factors seen in the real-life setting of AAS abuse.

In this case, we report a patient in acute mania admitted to Frederick Memorial Hospital in Frederick, Maryland. He had no prior history or family history of manic episodes. His symptoms were refractory to initial pharmacologic intervention.

The onset of his symptoms was likely related to the initiation of AAS use. However, his symptoms were likely potentiated by heavy daily cannabis use.

The patient showed a gradual improvement over the second week of his hospitalization. He was discharged on antipsychotics and scheduled to follow up with a therapist and psychiatrist.

Franey DG, Espiridion ED. Anabolic Steroid-induced Mania. Cureus 2018;10:e3163. Anabolic Steroid-induced Mania

"Unfortunately, the subject of the case later committed suicide as a result of AAS discontinuation and subsequent withdrawal-related depression."

Patient had a history of depression but they're sure his suicide was a result of AAS withdrawal related depression. Are these guys disciples of Pope?

They took an interesting approach with the main subject too. No mood stabilizers, just went straight to atypicals and Thorazine. They also discounted his history of mood disorder as a contributing factor. They didn't even have proof of AAS use, just second hand reports and his mumbling something about "deca" during his manic episode, but that didn't stop them from drawing the conclusion that, "Based on the history, the probable inciting factor was the initiation of AAS injections."

I'm beginning to see a pattern developing with these case reports.

 

[Dr JIM]

[OA] [GMAFB] Anabolic Steroid-induced Mania

There are numerous reports of the psychiatric effects of anabolic-androgenic steroid (AAS) use. However, these effects have not been clearly elicited in controlled clinical trials. This discrepancy is largely due to the presence of a variety of synergistic factors seen in the real-life setting of AAS abuse.

In this case, we report a patient in acute mania admitted to Frederick Memorial Hospital in Frederick, Maryland. He had no prior history or family history of manic episodes. His symptoms were refractory to initial pharmacologic intervention.

The onset of his symptoms was likely related to the initiation of AAS use. However, his symptoms were likely potentiated by heavy daily cannabis use.

The patient showed a gradual improvement over the second week of his hospitalization. He was discharged on antipsychotics and scheduled to follow up with a therapist and psychiatrist.

Franey DG, Espiridion ED. Anabolic Steroid-induced Mania. Cureus 2018;10:e3163. Anabolic Steroid-induced Mania

The authors make a mockery out of psychiatry formulating conclusions based upon conjecture ——- acute mania as a consequence of AAS and/or THC abuse.

 

[Michael Scally MD]

[OA] Sadaie MR, Farhoudi M, Zamanlu M, et al. What does the research say about androgen use and cerebrovascular events? Ther Adv Drug Saf 2018;9:439-55. SAGE Journals: Your gateway to world-class journal research

Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme).

New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT.

There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear.

Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective-destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes.

This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.

 

[Michael Scally MD]

[GMAFB] The Relationship Between the Big Five Personality Traits, Impulsivity, and Anabolic Steroid Use

BACKGROUND: The increase in the prevalence of anabolic-androgenic steroids (AAS) use has been the subject of study in the last decades. Several studies indicated a strong association between the use of AAS and the performance of risky behaviors mediated by factors such as aggression, impulsivity, depression, and anxiety.

OBJECTIVE: This study aimed to identify differences in personality trait, impulsivity, and the ability to delay gratification between AAS users and non-users that predispose or serve as a buffering mechanism against its usage and whether it is related to an increased likelihood of engaging in infidelity.

METHODS: Two hundred and twelve male volunteers (88 AAS users), aged between 21 and 36 years (M = 28.22), completed self-report measures of personality, impulsivity, delayed gratification, and attitudes toward infidelity. Multivariate analysis of variance and logistic regression were conducted to establish differences between AAS users and non-users.

RESULTS: The results showed that AAS users displayed an inability to delay gratification, a greater impulsivity, and a more benevolent attitude toward infidelity. AAS users obtained higher scores on openness and neuroticism, which was larger "off-cycle," although they presented lower scores on extraversion compared to the non-users group.

Regression analysis revealed that neuroticism, impulsivity, and delaying gratification scores were significant predictors of AAS usage. In addition, impulsivity functioned as a partial mediator in the relationship between neuroticism and AAS use.

CONCLUSION: The results of this research highlight a pivotal implication of impulsivity in AAS use in conjunction with neuroticism, openness, and extraversion traits.

Garcia-Argibay M. The Relationship Between the Big Five Personality Traits, Impulsivity, and Anabolic Steroid Use. Substance use & misuse 2018:1-11. https://www.tandfonline.com/doi/abs/10.1080/10826084.2018.1512630?journalCode=isum20

 

[CensoredBoardsSuck]

I think I'll conduct my own study on the hypothesis that these authors' latent homosexuality and subconscious sexual attraction to the AAS using male bodybuilder is the driving force behind their obsession to be around them, under the pretense of conducting research on AAS dependancy.

That hypothesis is as solid as any of theirs and I bet I could prove it. Do you think anyone will fund it?

 

[Michael Scally MD]

[GMAFB] Preventing Anabolic Steroid Abuse; A Long Way To Go

In 2017 Rich Piana, an American body builder and internet celebrity, suddenly died at the age of 46. Piana was not particularly successful as a competitive body builder, however, he became an internet sensation due to his massive body size and controversial videos about his long term anabolic steroid- and growth hormone abuse. Shortly after his death many speculated that his demise must have been related to his steroid addiction. The autopsy, however, was inconclusive about the cause of death.

…

Therefore, in order to design an effective strategy to prevent steroid abuse multiple issues need to be addressed.

What are the effects of exposing young men to images of unnaturally muscular men on the internet, in movies, TV shows, magazines, body building contests and cartoons?

What are the motives to start anabolic steroids in the first place?

Are anabolic steroids addictive?

How can we make anabolic steroids less accessible?

How can we effectively prevent or treat the adverse health effects of anabolic steroids?

Since most of these questions are largely unanswered, we still have a long way to go.

de Ronde W. Preventing anabolic steroid abuse; a long way to go. J Intern Med 2018. https://onlinelibrary.wiley.com/doi/abs/10.1111/joim.12858

 

[Michael Scally MD]

[Worthless Study] Exploring Anabolic-Androgenic Steroid Use and Teen Dating Violence Among Adolescent Males

BACKGROUND: Reports indicate that 4% of the adolescent males in 2015 had taken steroids without a doctor's prescription. Anabolic-androgenic steroids (AAS) are illicit drugs that have commonly been used to help build muscle mass. AAS use is associated with negative biological, psychological, and social side effects including substance use, suicidal behavior, and violent behavior.

OBJECTIVES: This exploratory study, guided by an integrated theoretical framework that included the General Aggression Model and the Biopsychosocial Model, examined the relationship between adolescent male AAS use and teen dating violence.

METHODS: This 1.1 cross-sectional, secondary data analysis was conducted using the 2013 and 2015 Massachusetts Youth Health Survey (MYHS). 1.7 Participants were high school-aged males with a total sample of 2,080. Primary data analysis was conducted using hierarchical logistic regression.

RESULTS: Findings suggested that adolescent males who used steroids at least once in their lifetime, compared to those who did not, had 1.1 greater odds of engaging in teen dating violence. Further, males who identified as a sexual minority had 1.1 greater odds of using anabolic-androgenic steroids, as were those who had at least one suicide attempt in the previous 12 months.

CONCLUSIONS: Adolescent male AAS use is associated with multiple psychosocial factors that practitioners, school personnel, and parents must be aware of.

Ganson KT, Cadet TJ. Exploring Anabolic-Androgenic Steroid Use and Teen Dating Violence Among Adolescent Males. Substance use & misuse 2018:1-8. https://www.tandfonline.com/doi/abs/10.1080/10826084.2018.1536723?journalCode=isum20

 

[Dr JIM]

I’ve read several reports about the addictive nature of AAS, but
what many researchers fail to realize, the entire lifestyle of PED abuse is what tends to be addictive rather than PEDs per se.

And IME the incidence of AAS abuse that correlates with addictive behaviors is particularly problematic in those youngsters on a quest for heightened self esteem and societal/peer group recognition.

How ironic and telling is it then that those searching for meaningful interpersonal relationships flock to PED forums in anonymity, and in doing so reach for drug rather than appropriate therapy for a number of psychosocial maladies

Ergo it’s the ability of PEDs to mask
a large number of insecurities that tends to be additive for many users.

And for the overwhelming majority I can only hope the abuse of AAS/PEDs will be one of several backward steps we all make in life.
JIM

 

[Old]

CONCLUSIONS: Adolescent male AAS use is associated with multiple psychosocial factors

How about: "Multiple psychosocial factors may lead some adolescent males to use AAS"

I’ve read several reports about the addictive nature of AAS, but
what many researchers fail to realize, the entire lifestyle of PED abuse is what tends to be addictive rather than PEDs per se.

The words "addition", "dependency" and "crisis" are ridiculously overused for sensationalization.

It’s similar to "Weapons of Mass Destruction". The term USED to mean nuclear, radiological, chemical, or biological agents. Now someone makes a pipe-bomb and the media cries, weapon-of-mass-destruction and a few thousand agents storm in. Then the cry is made, "we need more funds for security".


Take dependency. Type I diabetics are dependent on insulin. Is that evil? Do we need to launch ad campaigns against insulin? Ok, type II is entirely preventable and reversible in the early stage, but ...


I may be an addict because it is difficult to sleep without a good mattress and blankets. This addiction is so bad that when staying at cheap motels, it’s hard to sleep on those beds. Clearly need intervention and therapy. Why doesn't the government ban crappy beds? Or prevent me from staying at cheap motels? Isn't everyone else responsible for my behaviour?

While some drugs have a physiologically addictive risk (nicotine, meth, heroine), not all drugs additive, nor does everyone get addicted. Psychological addiction is blurry and has underlying issues driving such. JUST BECAUSE SOMEONE LIKES SOMETHING DOESN'T MEAN THEY ARE ADDICTED. There are key points that define actual addiction and it's not just because someone likes something or it feels good.


How about 'crisis'. More people die each year from traffic accidents than from opiods. If fact more have died than in WWI and its comparable to WWII. So they cry about the pitfalls of war and the 'opiod crisis' yet are silent about the 'auto crisis'. They even start wars involving 'oil-crisis', lol. Now automobiles are a lifestyle, not a requirement for existence. But we have structured a whole society dependent on cars. Is that not a true addiction in that this lifestyle is so damaging, just like actual drug addiction?

A key element of real addiction is continuing such behaviour in spite of serious negative consequences to one's life.

Here is just ONE YEAR of vehicles: "Every year the lives of approximately 1.35 million people are cut short as a result of a road traffic crash. Between 20 and 50 million more people suffer non-fatal injuries, with many incurring a disability as a result of their injury." Road traffic injuries

So in truth, mass transit has become mass destruction. It's just diffuse and we are accustomed to it. But don’t hold your breath waiting for a ban.


As for AAS, some, even on this forum, stopped as soon as they developed serious problems such as cardiac problems. Or warnings of liver or kidney distress. Or even just tired of the ups and downs of cycling. Others, in spite of knowing and/or feeling dangerous symptoms, continue - some to their death. Let the reader decide who is the addict ... or if all androgens are addictive.


In the end these words are used to manipulate people to allocate funds. Or people who seek purpose in manipulating other's lives so they can feel good about themselves.

Such people are best described in the movie Men In Black: "Y'know, I've noticed an infestation here. Everywhere I look, in fact. Nothing but undeveloped, unevolved, barely conscience pond scum, totally convinced of their own superiority as they scurry about in short pointless lives."

 

[Havah]

"Unfortunately, the subject of the case later committed suicide as a result of AAS discontinuation and subsequent withdrawal-related depression."

Patient had a history of depression but they're sure his suicide was a result of AAS withdrawal related depression. Are these guys disciples of Pope?

They took an interesting approach with the main subject too. No mood stabilizers, just went straight to atypicals and Thorazine. They also discounted his history of mood disorder as a contributing factor. They didn't even have proof of AAS use, just second hand reports and his mumbling something about "deca" during his manic episode, but that didn't stop them from drawing the conclusion that, "Based on the history, the probable inciting factor was the initiation of AAS injections."

I'm beginning to see a pattern developing with these case reports.

For most patients Olanzapine at 15 mg a day is a mood stabiliser tho

 

[Michael Scally MD]

Kaufman MJ, Kanayama G, Hudson JI, Pope HG. Supraphysiologic-dose anabolic-androgenic steroid use: a risk factor for dementia? Neuroscience & Biobehavioral Reviews 2019. https://www.sciencedirect.com/science/article/pii/S0149763418309515

Highlights
· Supraphysiologic-dose anabolic-androgenic steroid (sAAS) use starts by the mid-20s
· sAAS use occurs primarily in men aiming to increase muscularity
· sAAS use causes health problems including hypogonadism & excess oxidative stress
· These effects may increase synthesis & decrease elimination of Aβ & tau-P proteins
· sAAS use may cause early Aβ & tau-P increases and may enhance risk for dementia

Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels.

Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia.

Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.




Graphical Abstract

Supraphysiologic-dose anabolic-androgenic steroid use, which typically commences by the mid-20s, induces early-onset hypogonadism and excess oxidative stress. In turn, these abnormalities alter the function of many proteins involved in Aβ and tau-P synthesis and elimination. This could result in early-onset accumulation of these proteins in brain and increased risk for developing Alzheimer's Disease and its related dementias.

 

[Michael Scally MD]

[Mice] Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory

SIGNIFICANCE STATEMENT

17β-estradiol (E2) is produced from androgens via the action of the enzyme aromatase. E2 is known to be made in neurons in the brain, but its precise functions in the brain are unclear.

Using a novel forebrain neuron-specific aromatase knockout mouse model to deplete neuron-derived E2, the current study provides direct genetic evidence of a critical role for neuron-derived E2 to regulate rapid AKT-ERK and CREB-BDNF signaling in the mouse forebrain, and demonstrates that neuron-derived E2 is essential for normal expression of long term potentiation, synaptic plasticity, and cognitive function in both the male and female brain.

These findings suggest that neuron-derived E2 functions as a novel neuromodulator in the forebrain to control synaptic plasticity and cognitive function.

Lu Y, Sareddy GR, Wang J, et al. Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory. The Journal of Neuroscience 2019:1970-18. Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory

 

[Michael Scally MD]

Defreyne J, Kreukels B, T'Sjoen G, et al. No correlation between serum testosterone levels and state-level anger intensity in transgender people: Results from the European Network for the Investigation of Gender Incongruence. Hormones and Behavior 2019;110:29-39. https://www.sciencedirect.com/science/article/pii/S0018506X18304823

Highlights
· Aggression indicates externalizing anger through behaviour, whereas anger is a state of emotions.
· The WPATHSOC7 guidelines warn about increasing aggression in transgender men (TM) on testosterone treatment.
· A previous study in 56 TM reported no increase in aggression one year after initiation of testosterone therapy.
· The current study shows no correlation between anger intensity and exogenous/endogenous testosterone in TM.
· Testosterone seems safe in transgender people, even in presence of psychological/psychiatric vulnerability.

Introduction Anger is a state of emotions ranging from irritation to intense rage. Aggression implies externalizing anger through destructive/punitive behaviour. The World Professional Association for Transgender Health (WPATH) Standards of Care, Edition 7 (SOC7) guidelines warn about aggression in transgender men (TM) on testosterone treatment.

We aimed to assess whether anger intensity increases in TM and decreases in transgender women (TW) after initiation of gender affirming hormone therapy and to identify predictors for anger intensity in transgender people.

Methods This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Anger intensity was prospectively assessed in 898 participants (440 TM, 468 TW) by STAXI-2 (State-Trait Anger Expression Inventory-2) State Anger (S-Anger) during a three-year follow-up period, starting at the initiation of hormone treatment. Data were analysed cross-sectionally and prospectively.

Results There was no change in STAXI-2 S-Anger scores. At three, twelve and thirty-six months of gender affirming hormone therapy, STAXI-2 S-Anger scores were not correlated to serum testosterone levels, although there was a correlation with various psychological measures after three and twelve months.

TM experiencing menstrual spotting after three months had higher STAXI-2 S-Anger scores compared to those without (median 26.5 [18.0–29.8] versus 15.0 [15.0–17.0], P = 0.020).

Changes in STAXI-2 S-Anger scores were not correlated to changes in serum testosterone levels after three, twelve and thirty-six months in TM or TW.

Conclusions State-level anger intensity is associated with psychological and/or psychiatric vulnerability, but not exogenous testosterone therapy or serum testosterone levels in transgender people.