The Impact of Sex Hormones on Transcranial Magnetic Stimulation Measures of Cortical Excitability: A Systematic Review and Considerations for Clinical Practice.

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative for the treatment of major depressive disorder (MDD), although its clinical effectiveness varies substantially. The effects of sex hormone fluctuations on cortical excitability have been identified as potential factors that can explain this variability. However, data on how sex hormone changes affect clinical response to rTMS is limited. To address this gap, we reviewed the literature examining the effects of sex hormones and hormonal treatments on transcranial magnetic stimulation (TMS) measures of cortical excitability. Results show that variations of endogenous estrogen, testosterone, and progesterone have modulatory effects on TMS-derived measures of cortical excitability. Specifically, higher levels of estrogen and testosterone were associated with greater cortical excitability, while higher progesterone was associated with lower cortical excitability. This highlights the importance of additional investigation into the effects of hormonal changes on rTMS outcomes and circuit-specific physiological variables. These results call for TMS clinicians to consider performing more frequent motor threshold (MT) assessments in patients receiving high doses of estrogen, testosterone, and progesterone in cases such as in vitro fertilization, hormone replacement therapy, and gender-affirming hormonal treatments. It may also be important to consider physiological hormonal fluctuations and their impact on depressive symptoms and the MT when treating female patients with rTMS.