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In order to elucidate several neuromuscular mechanisms, and investigate cortical inhibition and peripheral muscle twitch force potentiation in women during the perimenopause, Pesonen et al [1] recently studied 63 perimenopausal women (48-55 years) categorized as early (EP, n = 25) or late (LP, n = 38) in accordance to their serum FSH levels and menstrual diaries. While EP women had irregular menstrual cycles and FSH levels < 25 IU/L, LP ones had irregular cycles and FSH levels > 25 IU/L. They studied motor evoked potential (MEP) and silent period (SP) elicited by transcranial magnetic stimulation (TMS), in the tibialis anterior muscle at 20%, 40%, and 60% of maximal voluntary contraction (MVC) levels, and twitch force potentiation in plantar flexors. They found that EP women showed a longer SP duration in 40% MVC condition and larger motor evoked potential amplitude in 20% MVC condition compared to LP women. They did not find differences in twitch force potentiation; although negatively correlating with FSH levels. Other factors, such as age, height, body mass index, or physical activity did not explain group differences. The authors of this preliminary study conclude that there are subtle modulations in both TMS-induced inhibitory and excitatory mechanisms and twitch force potentiation in women already in the late perimenopausal stage, suggesting that the decrease in estrogens may have an accelerating role in the aging process of neuromuscular control.


During the menopausal transition women are exposed to a decrease of estrogen secretion and thus an early decline in muscle force and motor function. These muscle quality and function changes, especially in lower limbs, are crucial, as they expose individuals to increased risk of falls [2]. In addition to changes in muscle properties, there are neurophysiological and cortical changes that play a major role in motor deficits related to the normal aging process. Estrogen decline has been related to neurophysiological changes, such as neuroinflammation, mitochondrial dysfunction, and synaptic decline [3]. In this study, the authors wanted to study muscle function and cortical control as well using a non-invasive tool such as TMS, and analyze SP and MEP according to the stage of the perimenopause and determine if progression of the menopausal stage affects motor control mechanisms. They found that EP women presented longer SP durations than LP ones during a moderate force production condition (40% MVC). MEP amplitudes were sensitive to the perimenopausal stage as in 20% MVC condition EP group showed larger MEP amplitudes and the same tendency remained in 40% MVC condition. Furthermore, an association was observed between twitch force potentiation and FSH. As participants were comparable in age, height, and body mass index, these factors could not explain the detected differences. Their results indicate a reduction in corticospinal inhibitory mechanisms observable already in late perimenopause. In addition, the authors found lower MEP amplitude in LP women as compared to EP ones indicating modulation of cortical excitability in perimenopausal stages. Reduced MEP amplitudes in older adults compared to young are a common finding, suggesting that the menopause may accelerate this modulation. These results suggest that progressive estrogen decline exerts a subtle modulation toward decreasing TMS-induced inhibition in the central nervous system and possibly decreasing muscle twitch force potentiation. Faultless interaction of inhibitory and excitatory processes is essential during appropriate motor control.

Despite the interesting findings, the authors recognize several limitations to their study such as small sample size, TMS stimulation performed without advanced navigation and information on individual brain images, leg motor areas were relatively small, located deep in the inter-hemispheric fissure and the optimal stimulation points are less segregated than those of hand muscles. Despite these limitations, results are interesting and further investigation in this field is warranted.

Peter Chedraui, MD, PhD
Instituto de Investigación e Innovación en Salud Integral
Universidad Católica de Santiago de Guayaquil, Guayaquil Ecuador


  1. Pesonen H, Laakkonen EK, Hautasaari P, et al. Perimenopausal women show modulation of excitatory and inhibitory neuromuscular mechanisms. BMC Womens Health. 2021;21(1):133.
  2. Bondarev D, Laakkonen EK, Finni T, et al. Physical performance in relation to menopause status and physical activity. Menopause. 2018;25(12):1432–41.
  3. Marin R, Diaz M. Estrogen interactions with lipid rafts related to neuroprotection. Impact of brain ageing and menopause. Front Neurosci. 2018;12:128.

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