Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala.

Rationale For several decades, elite athletes and a growing number of recreational consumers have used anabolic androgenic steroids (AAS) as performance enhancing drugs. Despite mounting evidence that illicit use of these synthetic steroids has detrimental effects on affective states, information available on sex-specific actions of these drugs is lacking. Objectives The focus of this review is to assess information to date on the importance of sex and its interaction with other environmental factors on affective behaviors, with an emphasis on data derived from non-human studies. Methods The PubMed database was searched for relevant studies in both sexes. Results Studies examining AAS use in females are limited, reflecting the lower prevalence of use in this sex. Data, however, indicate significant sex-specific differences in AAS effects on anxiety-like and aggressive behaviors, interactions with other drugs of abuse, and the interplay of AAS with other environmental factors such as diet and exercise. Conclusions Current methods for assessing AAS use have limitations that suggest biases of both under- and over-reporting, which may be amplified for females who are poorly represented in self-report studies of human subjects and are rarely used in animal studies. Data from animal literature suggest that there are significant sex-specific differences in the impact of AAS on aggression, anxiety, and concomitant use of other abused substances. These results have relevance for human females who take these drugs as performance enhancing substances and for transgender XX individuals who may illicitly self-administer AAS as they transition to a male gender identity.

The objective of this study was to determine whether physical performance during virtual environment (VE) tasks in the Computer-Assisted Rehabilitation Environment (CAREN) could differentiate between service members (SMs) with a history of traumatic brain injury (TBI) with and without comorbid post-traumatic stress disorder (PTSD). Data were obtained by independent review of clinical notes, objective outcomes, and validated questionnaires from 214 SMs (208 males) with a history of TBI assessed in the CAREN from 2010 to 2015. Three preliminary VEs acclimatized patients to the CAREN: Balance Balls, weight shifting on a static platform (timed); Balance Cubes, step shifting with and without platform motion (timed); and Continuous Road, flat ambulation (self-selected speed). Multiple regression analyses revealed that patients with comorbid TBI-PTSD were significantly slower in completing the VE tasks than patients without PTSD. Logistic regression showed that the Balance Cubes VE without platform motion significantly predicted diagnostic category (i.e., no PTSD vs. comorbid PTSD). In conclusion, in SMs with a history of TBI, physical performance on the CAREN effectively distinguished those with comorbid PTSD, as their performance was significantly slower than SMs without PTSD. These results portray the potential of the CAREN as a novel assessment tool in SMs with a history of TBI.