THE COMBINED CONTRACEPTIVE PILL FACILITATES SPIKE-TIMING-DEPENDENT PLASTICITY IN LONG-TERM USERS

Author(s): SPILLANE, P., CROSS, K., NÉDÉLEC, E., GOODALL, S., HICKS, K.M., ANSDELL, P., BOWERBANK, S., Institution: NORTHUMBRIA UNIVERSITY, Country: UNITED KINGDOM, Abstract-ID: 1455

INTRODUCTION:
Endogenous ovarian hormones have been shown to contribute to modulations in corticospinal excitability, and spike-timing-dependent plasticity (STDP; 1). However, little is known about the physiological effects of the synthetic versions of these hormones (e.g., ethinyl oestradiol), despite morphological changes in brain grey matter volume occurring with long-term use (2). The contraceptive pill is used by 151 million people worldwide and creates a daily micro cycle of synthetic hormones (~4-fold changes; 3), but the neurophysiological effects of these acute changes are yet to be investigated. Accordingly, the aim was to determine the effect of the monophasic combined oral contraceptive pill (mOCP) on corticospinal excitability and STDP.
METHODS:
Seventeen female participants (age: 23 ± 5 years) volunteered to take part, all were long term (45 ± 46 months) mOCP users. Participants visited the lab in two pill cycle phases: withdrawal and active. Visits comprised of baseline assessments of corticospinal excitability (motor evoked potential [MEP]/Mmax), short-interval cortical inhibition (SICI), and intracortical facilitation (ICF), recorded in the resting first dorsal interosseous. Participants then took their mOCP, and after 90 minutes of rest, assessments were repeated. This was followed by a paired associative stimulation (PAS) protocol, utilising ulnar nerve and transcranial magnetic stimulation (25 ms interstimulus interval) to induce STDP. To assess the time course of STDP, measurements were repeated at 15 and 30-minutes post PAS.
RESULTS:
Prior to taking the pill, corticospinal excitability (MEP/Mmax) was 12 ± 9% lower in the active phase (p < 0.001) compared to withdrawal, with no differences observed for SICI or ICF (p ≥ 0.203). 90 minutes after taking the pill, a further reduction in MEP/Mmax was observed in the active phase (86 ± 3% baseline, p < 0.001), with no change in the withdrawal phase (98 ± 3% baseline, p = 0.526). ICF increased pre-to-post regardless of phase (p = 0.007), but there were no changes in SICI (p = 0.347). PAS elicited an increase in MEP/Mmax in active only, whereby at 15-minutes (118 ± 5% pre-PAS, p < 0.001), and at 30-minutes responses were facilitated (119 ± 5% pre-PAS, p < 0.001). PAS failed to elicit any facilitation in the withdrawal phase at either 15 minutes (101 ± 5% pre-PAS) or 30 minutes (106 ± 5% pre-PAS, p ≥ 0.424).
CONCLUSION:
The present data contains two novel findings. Firstly, the mOCP has acute neuroactive effects, reducing corticospinal excitability. Secondly, that oral contraceptive users are only able to experience STDP during the active pill consumption phase, with blunted responses when not taking the pill. This has implications for neurorehabilitation and athletic activity, with individuals potentially needing to consider timing their pill consumption around motor performance.
1) Spillane et al., J Neurophys, 2026
2) Pletzer et al., Brain Res, 2015
3) Westhoff et al, Contraception, 2010