Anabolic androgenic steroid dependence and brain structure Lisa

Anabolic androgenic steroid dependence and brain structure Lisa Evju Hauger Norwegian National Advisory Unit on Substance Use Disorder Treatment

Anabolic androgenic steroids (AAS) • Synthetic derivatives of the male sex hormone testosterone • First isolated and synthesized in the late 1930’s. Performance enhancing in sports General public Kanayama et al. 2017

AAS – a major new form of substance abuse Pope et al. 2014 Kanayama et al. 2009

Effects of AAS • Androgenic (masculinizing) and anabolic (protein-synthesizing) effect • Often administered in cycles, with drug-free periods in between On cure Positive mood More energy Better selfconfidence Long-term use Physical, psychological and cognitive sideeffects. Many users experience withdrawal symptoms in drug-free periods Thiblin et al. 2005 Banks et al. 2012

AAS dependence Characterized by withdrawal symptoms and continued use despite the experience of adverse effects

Dependency - mechanisms Body image HPT suppression Hypogonodal Fatigue, loss of libido, depression Neuroendocrine processes Hedonic mechanisms Kanayama et al. 2010

Dependence and brain correlates • Addictive drugs – structural plasticity • AAS – neurotoxic effects • Long-term ASS use – structural and functional brain alterations The aim was to investigate if there is any structural brain differences between dependent and non-dependent AAS users Ersche et al. 2013 Estrada et al. 2006 Bjørnebekk et al. 2016

“Long-term androgenic anabolic steroid use on brain, cognitive functioning and emotional processing” • 81 current or previous AAS users 43 dependent, 38 non-dependent

Self-reported physiological side-effects Dependent (n=43) Memory problems Non-dependent (n=38) % 16 51 Gynecomastia 32 Sexual dysfunction 40 34 58 Reduced sex drive 61 Cardiomypathy or arterial fibrilation 26 26 Acne 54 Blood pressure 29 Cholesterol Liver related issues Kidney related issues 54 24 27 18 16 47 26 58 81

Self-reported psychological side-effects Dependent (n=43) Non-dependent (n=38) % Reduced Appetite 11 49 Sleep problems 32 Mood swings 29 Short fuse Fatigue Depression 49 32 Aggression Anxiety 61 56 26 - 65 20 34 67 37 63

Main findings brain Largest cluster frontal and prefrontal regions bilaterally controlling for previous and current drug abuse – significant effect remained in precentral and orbitofrontal regions The dependent AAS group showed significantly larger nucleus accumbens volume

Implications • Prefrontal cortex numerous higher order cognitive functions • Orbitofrontal cortex important role in addiction • Lack of inhibitory control helps explain continuation despite adverse side-effects

Enlargement of NA and thinner cortex in prefrontal regions is also seen in other dependencies shared vulnerability for the development of dependence in general?

The everlasting causality question… Premorbid vulnerabilities vs. AASs effect May not be mutually exclusive.

Summary • Dependent AAS users had structural brain alteration similar to that of other drugs of abuse gives further support to the addictive properties of AAS’s • The vast majority of dependent users seem to struggle with complex issues tailor-made interdisciplinary programs are needed to obtain optimal results.

Thank you! Astrid Bjørnebekk Project leader Prof. Anders M. Fjell & Prof. Kristine B. Walhovd Ingunn R. Hullstein Norwegian doping laboratory Radiologist Paulina Due-Tønnesen Lars Tjelta Westlye Contact information: Lisa Evju Hauger Oslo University Hospital haulis@ous-hf. no www. tsb. no Marie L. Jørstad

Longitudinal follow-up after 3. 5 år 100 AAS users & 100 non-users Ø Ø Ø Neuropsychological tesing Psychiatric screening Social cognition MRI f. MRI Hormon analysis Cardiovascular examination Vibeke Almaas Per Medbøe Thorsbye Ingrid Amalia Havnes