Non-Invasive Brain Stimulation and Sex/Polypeptide Hormones in Reciprocal Interactions: A Systematic Review

A better understanding of interindividual differences and the development of targeted therapies is one of the major challenges of modern medicine. The sex of a person plays a crucial role in this regard. This systematic review aimed to summarise and analyse available evidence on the mutual interactions between non-invasive brain stimulation and sex/polypeptide hormones. The PubMed database was searched from its inception to 31 March 2023, for (i) studies that investigated the impact of sex and/or polypeptide hormones on the effects induced by non-invasive brain stimulation, or (ii) studies that investigated non-invasive brain stimulation in the modulation of sex and/or polypeptide hormones. Eighteen studies (319 healthy and 96 disabled participants) were included. Most studies focused on female sex hormone levels during the menstrual cycle. The later follicular phase is associated with a weak between hemispheric and intracortical inhibition, strong intracortical facilitation, and high stimulation-induced neural and behavioural changes. The opposite effects are observed during the luteal phase. In addition, the participant's sex, presence and/or absence of real ovulation and increase in oestradiol level by chorionic gonadotropin injection influence the stimulation-induced neurophysiological and behavioural effects. In Parkinson's disease and consciousness disorders, the repetitive application of non-invasive brain stimulation increases oestradiol and dehydroepiandrosterone levels and reduces disability. To date, male hormones have not been sufficiently included in these studies. Here, we show that the sex and/or polypeptide hormones and non-invasive brain stimulation methods are in reciprocal interactions. This may be used to create a more effective and individualised approach for healthy individuals and individuals with disabilities.