Rationale: Previous research has demonstrated the neuroactive effects of ovarian hormones across the menstrual cycle [1], however it remains less clear how the cessation of hormone production across the menopause influences motor cortical properties. Additionally, it is currently unknown how nervous system adaptation (neuroplasticity) is mediated by endogenous and exogenous hormones across the human lifespan.
Methods: Participants’ menopausal status was classified according to NICE guidelines on the diagnosis and management of menopause, with 12 pre-menopausal (age: 29 ± 7 years), 7 peri-menopausal (49 ± 4 years), 5 post-menopausal females (54 ± 5 years), and 7 females using HRT (54 ± 4 years) taking part in the study. Participants underwent a baseline neurophysiological assessment, including electrical stimulation of the median nerve and transcranial magnetic stimulation of the motor cortex to assess corticospinal excitability and intracortical inhibition and facilitation (SICI and ICF). Then, a paired associative stimulation (PAS) protocol was performed with electrical stimulation at 300% perceptual threshold delivered 25 ms prior to TMS at 120% motor threshold. 200 paired stimuli were delivered at 0.2 Hz, which were then followed with repeated neurophysiological assessments immediately, 10-, 20- and 30-minutes after PAS.
Results: No differences between groups were observed at baseline for corticospinal excitability (p = 0.322), SICI (p = 0.570) or ICF (p = 0.961). In response to the PAS protocol, only the pre-menopausal group experienced a significant increase in corticospinal excitability (+69%, p < 0.001), compared to peri- (+38%, p = 0.136) and post-menopausal females (+4%, p = 0.868). HRT users experienced a +53% increase in corticospinal excitability, however, this did not reach statistical significance (p = 0.084).
Conclusions: Motor cortical neuroplasticity was only evident in pre-menopausal females, implying that the cessation of ovarian hormone production impairs the nervous system’s ability to adapt to novel stimuli. HRT could present an exogenous method of attenuating this menopause-related effect, which has implications for functional capacity in health and disease.