Harms associated with inhalant misuse in adolescent females – a review of the pre-clinical and clinical evidence

Background: Inhalant misuse, or the misuse of products containing toluene is common in adolescents, and is associated with diverse physiological and psychological harms. Females comprise over half those who misuse inhalants in adolescence, however, the majority of the evidence has been derived from male-only or mixed-sex studies without exploration of sex differences. Female adolescence is a critical maturational period with potential for growth, reproductive, cognitive and psychological harms that may lead to long-term health consequences. We therefore summarise evidence of female-specific harms arising from inhalant misuse. Methods: We synthesised pre-clinical and clinical studies of inhalant misuse which were conducted in females, or where sex-differences were reported, into a narrative literature review. Results: Females experience growth impairments and metabolic dysfunction arising from inhalant misuse, but data on sex-differences are inconclusive. Inhalant misuse in early adolescence may impact menarche and subsequent reproductive capacity, but studies have predominantly focused on the effects of inhalants on offspring rather than on the exposed female. There is limited evidence of sex-differences in relation to cognitive outcomes following exposure to inhalants in pre-clinical models. Females are at an increased risk of psychological harms associated with inhalant misuse, particularly depression and suicidal behaviour. Conclusions: The type and magnitude of harms associated with inhalant misuse are sex-specific, but data are limited. We recommend that both pre-clinical and clinical studies of inhalant misuse include both males and females, and should specifically test for and report sex-differences. This can be used to build an evidence base for screening and interventions tailored to females.