AAS – CNS Effects

[Michael Scally MD]

Competitive Bodybuilding: Fitness, Pathology, or Both?

The sport of competitive bodybuilding requires an intense regimen of weightlifting and dieting, often aided with muscle-building or fat-burning drugs, and culminating in an on-stage posing competition. Despite these rigorous demands, competitive bodybuilding is popular, with thousands of competitions performed annually around the world.

Although many studies have addressed the psychological features of various sports and the athletes who compete in them, few have examined the psychological aspects of bodybuilding. Even fewer studies have specifically examined competitive bodybuilders, as opposed to the much larger group of “recreational” bodybuilders who do not compete.

The limited available literature suggests that competitive bodybuilders may show an increased risk for four categories of psychopathology:
· muscle dysmorphia,
· eating disorders,
· abuse of appearance- and performance-enhancing drugs, and
· exercise dependence.

However, in each of these categories, one must carefully distinguish between the planned and dedicated behaviors required for success in the sport, as opposed to frankly pathological behaviors that impair social or occupational function, cause subjective distress, or lead to adverse health consequences.

Future work should attempt to better assess the nature and prevalence of these conditions among competitive bodybuilders, with perhaps greatest attention to the issue of drug use.

Steele IH, Pope HG, Jr., Kanayama G. Competitive Bodybuilding: Fitness, Pathology, or Both? Harvard Review of Psychiatry 9000;Publish Ahead of Print. https://journals.lww.com/hrpjournal/Fulltext/publishahead/Competitive_Bodybuilding__Fitness,_Pathology,_or.99947.aspx

 

[Michael Scally MD]

Cognitive Performance and Structural Brain Correlates in Long-Term Anabolic-Androgenic Steroid Exposed and Nonexposed Weightlifters

OBJECTIVE: To test for associations between long-term anabolic-androgenic steroid (AAS) use and cognitive functioning, and establish a candidate neuronal basis by assessing the associations between cognitive performance and brain morphology both in users and nonusers.

METHOD: Eighty four previous or current AAS-users and 69 non-AAS-using male weightlifters aged 19-75 years (mean 32.6, SD 8.8) underwent MRI of the brain and a comprehensive neuropsychological test battery. Performance on fine motor speed, speed of processing, learning and memory, working memory, executive functioning, and problem solving was compared between the groups, and between AAS users with short versus long AAS exposure. Associations between cognitive scores and regional cortical thickness and arealization defined using FreeSurfer were tested using linear models.

RESULTS: Relative to nonexposed, AAS-exposed weightlifters performed significantly worse on several cognitive domains, independent of age, education, verbal IQ, and exposure to classical drugs of abuse. Strongest effects were observed for speed of processing (etap2 = .07), working memory (etap2 = .08) and problem solving (etap2 = .09). Longer duration of AAS-use was associated with poorer memory function (etap2 = .11). Within AAS users, individuals with better memory and working memory performance had with thicker frontoparietal cortex and larger medial frontal surface area, respectively.

CONCLUSIONS: Prolonged high-dose AAS use is associated with poorer cognitive function across multiple domains, and the observed regional associations between cortical brain morphometry and memory and working memory performance may suggest differential brain-based mechanisms. The public, health care professionals, and policymakers should be aware that use of AAS in large doses potentially could lead to poorer brain health and cognition.

Bjornebekk A, Westlye LT, Walhovd KB, Jorstad ML, Sundseth OO, Fjell AM. Cognitive performance and structural brain correlates in long-term anabolic-androgenic steroid exposed and nonexposed weightlifters. Neuropsychology 2019;33:547-59. https://psycnet.apa.org/record/2019-23039-001

 

[Michael Scally MD]

Effects of Testosterone Supplementation on Separate Cognitive Domains in Cognitively Healthy Older Men

Highlights

What is the primary question addressed by this study?
· Among randomized clinical trials (RCTs) published in the last decade, does testosterone supplementation improve cognitive performance in cognitively healthy older men?

What is the main finding of this study?
· Comparison of placebo versus treatment group pre and post supplementation showed significant improvements in the treatment group for cognition as a whole, psychomotor speed and executive function, only in randomized clinical trials (RCTs) that demonstrate an increase in total testosterone levels after supplementation.

What is the meaning of the finding?
· Our results evidence the potential for testosterone supplementation to improve cognitive performance and support the differential effects of testosterone on individual cognitive domains.

BACKGROUND: An increasing body of literature suggests a positive, neuroprotective effect for testosterone on cognition in older men. However, randomized clinical trials (RCTs) examining the effects of testosterone supplementation (TS) on cognitive function have been inconclusive.

OBJECTIVE: To investigate the potential for TS to prevent cognitive decline in otherwise cognitively healthy older men, by examining the differential effects of TS on cognitively healthy older men in RCTs.

METHODS: Comprehensive search of electronic databases, conference proceedings, and grey literature from 1990 to 2018 was performed to identify RCTs examining the effects of TS on cognition before and after supplementation, in cognitively healthy individuals.

RESULTS: A final sample of 14 eligible RCTs met inclusion criteria. Using pooled random effects expressed as Hedge's g, comparison of placebo versus treatment groups pre- and postsupplementation showed improvements in the treatment group in executive function (g (11)=0.14, 95% confidence interval [CI]: 0.03-0.26, z=0.56, p=0.011).

However, it was noted that two studies in our sample did not report a significant increase in mean serum total testosterone (TT) levels in the treatment group after supplementation. Following exclusion of these studies, analysis indicated improvement in the treatment group for the overall cognitive composite (g (11)=0.18, 95% CI: 0.02-0.33, z=2.18), psychomotor speed (g (3)=0.22, 95% CI: 0.01-0.43, z=2.07) and executive function (g (9)=0.15, 95% CI: 0.03-0.28, z=2.35).

No significant differences were noted for the global cognition, attention, verbal memory, visuospatial ability or visuospatial memory domains.

CONCLUSION: Overall, our findings support the potential for TS as a preventative measure against cognitive decline, although the effect sizes were small. These findings warrant further observational studies and clinical trials of good methodological quality, to elucidate the effect of TS on cognition.

Tan S, Sohrabi HR, Weinborn M, et al. Effects of Testosterone Supplementation on Separate Cognitive Domains in Cognitively Healthy Older Men: A Meta-analysis of Current Randomized Clinical Trials. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 2019. https://www.sciencedirect.com/science/article/pii/S106474811930363X?via%3Dihub

 

[Michael Scally MD]

Pair-Bonding, Fatherhood, and the Role of Testosterone

Highlights
· The Challenge Hypothesis (CH) concerns the dynamics of male life-history strategies.
· The CH predicts that testosterone (T) mediates shifts between mating and parenting.
· In humans, pair-bonding and fatherhood generally correspond to lower T.
· We meta-analyze 114 effects to quantify magnitudes of predicted CH effects in men.
· We find both robust effects and evidence of selective reporting.

Males of many species must allocate limited energy budgets between mating and parenting effort. The Challenge Hypothesis provides a framework for understanding these life-history trade-offs via the disparate roles of testosterone (T) in aggression, sexual behavior, and parenting.

It predicts that males pursuing mating opportunities have higher T than males pursuing paternal strategies, and in humans, many studies indeed report that men who are fathers and/or pair-bonded have lower T than childless and/or unpaired men. However, the magnitude of these effects, and the influence of methodological variation on effect sizes, have not been quantitatively assessed.

We meta-analyzed 114 effects from 66 published and unpublished studies covering four predictions inspired by the Challenge Hypothesis. We confirm that pair-bonded men have lower T than single men, and fathers have lower T than childless men. Furthermore, men more oriented toward pair-bonding or offspring investment had lower T.

We discuss the practical meaningfulness of the effect sizes we estimate in relation to known factors (e.g., aging, geographic population) that influence men's T concentrations.

Grebe NM, Sarafin RE, Strenth CR, Zilioli S. Pair-bonding, fatherhood, and the role of testosterone: A meta-analytic review. Neuroscience and biobehavioral reviews 2019;98:221-33. https://www.sciencedirect.com/science/article/pii/S0149763418304391?via%3Dihub

 

[Michael Scally MD]

Exogenous Testosterone Increases Sensitivity To Moral Norms In Moral Dilemma Judgements

Moral dilemma judgements frequently involve decisions where moral norms and the greater good are in conflict. The current preregistered study tested the effect of the steroid hormone testosterone on moral dilemma judgements using a double-blind administration of testosterone or placebo.

Counter to predictions, testosterone administration led to increased inaction in moral dilemmas where harmful actions prohibited by moral norms increase overall well-being. Using a mathematical model to disentangle sensitivity to consequences, sensitivity to moral norms and general preference for inaction versus action, analyses further revealed that testosterone administration influenced judgements by increasing sensitivity to moral norms.

Exploratory analyses suggested the opposite pattern for endogenous testosterone measured at baseline, in that higher levels of endogenous testosterone were associated with lower sensitivity to moral norms. The results indicate that the role of testosterone in moral judgements is more complex than suggested by previous findings.

PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 13 November 2017. The protocol, as accepted by the journal, can be found at Exogenous Testosterone Increases Sensitivity to Moral Norms in Moral Dilemma Judgments (1).

Brannon SM, Carr S, Jin ES, Josephs RA, Gawronski B. Exogenous testosterone increases sensitivity to moral norms in moral dilemma judgements. Nat Hum Behav 2019. Exogenous testosterone increases sensitivity to moral norms in moral dilemma judgements

 

[Michael Scally MD]

Who or what do young adults hold responsible for men's drunken violence?

BACKGROUND: Men are more likely than women to perpetrate serious violence when they have consumed alcohol, but alcohol does not affect all men in the same way. This paper considers young adults' attribution about agency (the capacity to act) in men's drunken violence.

METHODS: Interviews about alcohol use in night-time venues, streets or private parties were conducted with 60 young adults aged 18-24 in Melbourne, Australia, and analysed thematically. Participants included seven men who identified as having initiated violence when drunk.

RESULTS: Some interviewees stated that men chose to be violent, or that men's violence when they were drunk was purposeful and therefore involved some component of choice. However, much alcohol-related violence enacted by young men was understood (both by men who reported violence and by other young adults) as impelled by forces outside their control.

These forces were:
· diffusely defined effects of drinking alcohol;
· proclivities of men and masculinity, and
· the interaction of alcohol and men's bodies to override capacity for judgement and produce an irresistible urge to fight.

The latter was at times explained as caused by the mutually reinforcing actions of alcohol and testosterone, providing a particularly persuasive account of men's violence as biologically-determined.

CONCLUSION: These categories encapsulate a set of discursive resources that contribute to the rationalisation, naturalisation and production of men's violence. Participants tended to regard alcohol, masculinities and TESTOSTERONE as inciting violence predictably and consistently, suggesting that men themselves had relatively little agency over its occurrence.

In contrast, research evidence indicates that these actors do not cause violence in any uniform way and that their effects are contingent on changing configurations of factors.

Highlighting discrepancies between young adults' understandings of responsibility for men's drunken violence, and those expressed in research, presents additional opportunities for intervention.

MacLean S, Demant J, Room R. Who or what do young adults hold responsible for men's drunken violence? The International journal on drug policy 2019. Who or what do young adults hold responsible for men’s drunken violence? - ScienceDirect

 

[Michael Scally MD]

[OA] Neuropsychiatric and Behavioral Involvement in AAS Abusers

Background and Objectives: Anabolic androgenic steroids (AASs) are a complex group of molecules that include both steroidal androgens and synthetic compounds, derived from testosterone.

AASs are commonly used to support pharmacological therapy in cases of primary or secondary hypogonadism, major burns, and neoplastic cachexia. Their prolonged and supra-physiological consumption can provoke several adverse effects on various organs and systems.

Among these, the physiopathological mechanisms that induce neuropsychiatric disorders related to AAS abuse are poorly known. For this reason, the proposed review aims to retrace the pathway of action of testosterone to focus on the effects on the central nervous system and specifically highlight the effects of AASs on neuropsychiatric and behavioral functions, as well as on lifestyle.

Materials and Methods: This review was conducted using PubMed and Google Scholar databases. On these database websites, we searched for articles from 1 January 1980 to March 2019 using the key terms: "AAS," "Anabolic Androgenic Steroids," "brain," and "neurology."

Results: The use of AASs through self-administration yields circulating androgens levels, inducing neuron apoptosis, which is linked to thinner cortex and, in general, less cortical volume. The same alterations affect the putamen. These differences were more evident when correlated with longer use.

From a functional point of view, prolonged AAS consumption seemed to be related to lower connectivity between amygdala and frontal, striatal, limbic, hippocampal and visual cortical areas. On the other hand, AAS use seems to negatively condition the positive effects of the sport exercise, reducing its important anti-apoptotic and pro-proliferative functions on the hippocampus, implicated in anxiolytic control.

Conclusion: This review clarifies the major aspects of the side effects related to AAS use/abuse highlighting the complex mechanisms on neuropsychiatric and cognitive pathological alterations and also the emotional and behavioral dysfunctions.

Bertozzi G, Salerno M, Pomara C, Sessa F. Neuropsychiatric and Behavioral Involvement in AAS Abusers. A Literature Review. Medicina (Kaunas, Lithuania) 2019;55. https://www.mdpi.com/1010-660X/55/7/396/htm

 

[Michael Scally MD]

RUFKM ...

Domestic terrorist Cesar Sayoc faces sentencing today

 

[Michael Scally MD]

RUFKM ...

Domestic terrorist Cesar Sayoc faces sentencing today

Domestic terrorist Cesar Sayoc faces sentencing today [Pope: AAS … ]

Both Dr. Harrison G. Pope, Jr., M.D., a leading psychiatrist and expert in the field of steroid use, and Dr. Michael First, M.D., an expert in clinical psychiatry, believe Mr. Sayoc’s actions here were the product of his long-untreated mental illness, compounded by excessive steroid use.

https://www.courthousenews.com/wp-content/uploads/2019/07/Sayoc-Sentencing-Submission.pdf

 

[Millard]

RUFKM ...

Domestic terrorist Cesar Sayoc faces sentencing today

It's not the first time. Dr. Pope makes a nice side income pandering to defense attorneys as an "expert witness".

And then there's Michael First of Columbia University :

 

[Millard]

Domestic terrorist Cesar Sayoc faces sentencing today [Pope: AAS … ]

Both Dr. Harrison G. Pope, Jr., M.D., a leading psychiatrist and expert in the field of steroid use, and Dr. Michael First, M.D., an expert in clinical psychiatry, believe Mr. Sayoc’s actions here were the product of his long-untreated mental illness, compounded by excessive steroid use.

https://www.courthousenews.com/wp-content/uploads/2019/07/Sayoc-Sentencing-Submission.pdf

 

[Michael Scally MD]

Dr. Michael B. First of Columbia University came to similar conclusions. Dr. First found that Mr. Sayoc was suffering from a personality disorder and the effects of a “steroid-induced mental disorder with manic-like features” at the time he committed these offenses, and that the “psychiatric changes caused by his steroid use, working in concert with his maladaptive personality traits like emotional lability and suspiciousness caused him to act out is self-destructive way.”

 

[Millard]

View attachment 116321

It's the first time I've heard of steroid-induced anosognosia. Google isn't familiar with it either. Is it possible that Dr. Pope made it up specifically for the Sayoc trial?

 

[Michael Scally MD]

[Kill Me Now!] A Review On The Health Hazards Of Anabolic Steroids

In 1935, testosterone was finally isolated and synthesized, and testosterone-analogs soon entered the world of sports. Today, the use of these performance-enhancing agents is no longer confined to the elite sports milieu, and the lifetime prevalence of anabolic steroid use among men is estimated to be around 6%.

Unfortunately, these drugs are not without side effects, and the most common somatic adverse drug reactions are gynaecomastia, infertility, testicular dysfunction, and acne. Furthermore, the use of AAS is associated with a variety of psychiatric disorders and antisocial behaviour.

Horwitz H, Christoffersen T. A review on the health hazards of anabolic steroids. Adverse Drug Reaction Bulletin 2019;317. A review on the health hazards of anabolic steroids : Adverse Drug Reaction Bulletin

 

[Michael Scally MD]

It's the first time I've heard of steroid-induced anosognosia. Google isn't familiar with it either. Is it possible that Dr. Pope made it up specifically for the Sayoc trial?

WTF! Pope's research is some of the very worst. He has dug a hole so deep he sees no way out except to make up more crap.

 

[Michael Scally MD]

Anabolic-Androgenic Steroids and The Risk of Imprisonment

Highlights
· Anabolic-androgenic steroid users had a 9-fold higher crime rate compared to controls.
· By end of follow-up 18.5% of the AAS users had been imprisoned due to violent crimes.
· This increased rate of crime was not attributable to common socio-economic factors.

BACKGROUND: The use of Anabolic-Androgenic Steroids (AAS) has been associated with increased aggressiveness and violent behavior. We therefore investigated the proposed correlation between the use of AAS and criminality while controlling for important socio-economics covariates and for psychiatric comorbidity.

METHODS: The primary endpoints were prison sentences, and time to first prison sentence. A retrospective matched cohort study design consisting of 545 males, who tested positive for AAS in Danish gyms during the period January 3, 2006 to January 31, 2017. They were matched with 5450 randomly chosen male controls. Data were cross-referenced with national register information on education, employment status, substance abuse and psychiatric comorbidity. In addition, 638 males sanctioned because they rejected to participate in the doping control and 6380 controls were used as a replication cohort.

RESULTS: Already at baseline, 20.6% of the AAS users had a previous prison sentence whereas the rate was 3.7% in the control cohort (p < 0.0001). During the follow-up period the cumulative prevalence increased to 29.5% and 4.9%, respectively (unadjusted HR 9.15, 95% CI 6.33-13.20). The associations remained highly significant after controlling for socio-economic factors, drug abuse and psychiatric comorbidity. The results could be replicated in a similar cohort.

CONCLUSION: Our study shows that AAS users have a 9-fold increased risk of being convicted of a crime compared to matched controls, randomly chosen from the general population. This association could not be explained by common socioeconomic factors or by psychiatric comorbidity.

Christoffersen T, Andersen JT, Dalhoff KP, Horwitz H. Anabolic-androgenic steroids and the risk of imprisonment. Drug and alcohol dependence 2019;203:92-7. https://www.sciencedirect.com/science/article/abs/pii/S0376871619302364

 

[Michael Scally MD]

[OA] Superior Sagittal Venous Sinus Thrombosis in a Patient with Illicit Testosterone Use

Cerebral venous sinus thrombosis is a challenging diagnosis due in part to its variable clinical presentation and rarity. The annual incidence ranges from 0.22 to 1.57 per 100,000. The etiology of such disease is related to hypercoagulability states. Although illicit androgen use is a well-known cause of prothrombotic states, its risk of causing cerebral venous sinus thrombosis has been infrequently reported.

We present the case of a 33-year-old male with no known past medical history who presented to the emergency department (ED) with persistent seizure activity, neurological deficits, and history of worsening headaches who was found to have an extensive superior sagittal sinus thrombosis on imaging. Radiologic findings demonstrated pathognomonic findings of cord sign and delta sign, the previous being highly specific but of low incidence.

An inconclusive hypercoagulability workup prompted further questioning which revealed illicit androgenic anabolic steroid use. Prompt treatment with anticoagulation and anti-seizure medication was pursued with full resolution of his neurologic symptomatology.

Hashmi A, Kim P, Ahmad S W, et al. Superior Sagittal Venous Sinus Thrombosis in a Patient with Illicit Testosterone Use. Cureus. 2019;11(8):e5491. https://www.cureus.com/articles/225...is-in-a-patient-with-illicit-testosterone-use

 

[Michael Scally MD]

[OA] A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse.

Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated.

In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming.

Tsatsakis A, Docea AO, Calina D, et al. A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse. Journal of clinical medicine 2019;8. A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse

 

[Michael Scally MD]

[OA] Does testosterone impair men's cognitive empathy? [No]

The capacity to infer others' mental states (known as ‘mind reading’ and ‘cognitive empathy’) is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia.

Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small sample studies with mixed evidence.

We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (n = 243 and n = 400), using two different testosterone administration protocols.

We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.

Nadler A, Camerer Colin F, Zava David T, et al. Does testosterone impair men's cognitive empathy? Evidence from two large-scale randomized controlled trials. Proceedings of the Royal Society B: Biological Sciences 2019;286:20191062. https://doi.org/10.1098/rspb.2019.1062

 

[Michael Scally MD]

‘Shades of Grey’: The Ethics of Social Work Practice in Relation to Un-prescribed Anabolic Androgenic Steroid Use

This paper reflects on some of the ethical dilemmas that social workers face when assessing risk in relation to those using substances. It explores how legislation and societal factors can impact not just on people’s choices and decisions but also on their ‘vulnerability’ and access to services.

Vulnerability, a contested term, is linked, in this paper, to assessment of risk. There are ethical issues that arise when assessing risk with people who use Anabolic Androgenic Steroids (AAS) from both service user and professional perspectives. These ethical issues concern a person’s right to choose and make potentially harmful decisions.

The paper argues that using substances such as AAS in and of itself does not suffice to make a person vulnerable but this does not mean that people using AAS are not in need of support. It suggests that there may be some groups of people who are more at risk to starting AAS use and that social workers should be aware of these.

It also recommends the need for further qualitative research to understand the reasons for starting use and support to help people stop using AAS.

Harvey O. ‘Shades of Grey’: The Ethics of Social Work Practice in Relation to Un-prescribed Anabolic Androgenic Steroid Use. Practice 2019;31:239-58. https://doi.org/10.1080/09503153.2018.1510480