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Journal of the Pediatric Orthopaedic Society of North America logoLink to Journal of the Pediatric Orthopaedic Society of North America
. 2026 Aug 21;17:100429. doi: 10.1016/j.jposna.2026.100429

Exploring the Impact of Ovarian Hormones on Cortical Drive and Quadriceps Performance in Uninjured Female Athletes

Anne Leung 1,2,3,⁎, Elizabeth Wellsandt 4,5, Philip Malloy 6, Dustin Grooms 7, Ryan Zarzycki 1,8
PMCID: PMC13675895  PMID: 42892945

Abstract

Background

Ovarian hormones fluctuate across the menstrual cycle (MC) and differ between oral contraceptive (OC) users and naturally menstruating (NM) individuals. Hormones may affect cortical drive to peripheral muscles through excitatory effects of estradiol and inhibitory effects of progesterone on the central nervous system. The impact of hormones on cortical drive is poorly understood. This study aimed to (1) determine the effects of MC phase and OC use on cortical drive and quadriceps performance and (2) determine the relationship between ovarian hormones and these outcomes. We hypothesized that cortical drive will differ between MC phases in NM individuals but not in OC users. Cortical drive will be positively associated with circulating estradiol.

Methods

Fourteen NM individuals and 11 OC users completed two time points (high hormone: NM mid-luteal, OC active pill and low hormone: NM early follicular, OC placebo). Hormone concentrations were quantified using enzyme-linked immunosorbent assays. Quadriceps performance (isometric peak torque [PTISOM] and rate of torque development) was measured using an isokinetic dynamometer. Corticospinal excitability and intracortical excitability (short-interval intracortical inhibition [SICI] and intracortical facilitation) were assessed using transcranial magnetic stimulation. Linear mixed-effect models were used to examine hormone status, phase, and interaction effects. Linear regression determined associations between hormones, cortical drive, and strength.

Results

There were no significant main effects or interactions for any cortical drive measure. There was a phase by hormone status interaction on the rate of torque development from 0 to 100 ms (RTD100), with a greater RTD100 at the high hormone phase than at the low hormone phase in the NM group but no difference between time points in the OC group. There was a main effect of phase on PTISOM, with a greater PTISOM at the low hormone phase regardless of hormone status. SICI was negatively associated with estradiol. RTD100 was positively associated with progesterone and moderated by hormone status.

Conclusions

MC phase did not impact cortical drive but did impact quadriceps performance. There were between-phase differences in speed of contraction among NM individuals but not among OC users. A higher progesterone level was associated with faster speed of contraction, especially among NM participants.

Key Concepts

  • (1)

    Corticospinal and intracortical excitability did not differ by menstrual cycle (MC) phase or oral contraceptive (OC) use.

  • (2)

    Quadriceps rate of torque development was associated with progesterone concentration and varied across the MC, suggesting hormone expression influenced the rate of torque development (RTD) (speed of contraction).

  • (3)

    The influence of endogenous ovarian hormones on RTD (speed of contraction) differed between OC users and naturally menstruating individuals.

Level of Evidence

II

Keywords: ACL, Menstrual cycle, Ovarian hormones, Corticospinal excitability, Quadriceps performance

Introduction

Ovarian hormone (estradiol and progesterone) expression is widely variable across individuals [1,2]. Previous endocrinology and exercise physiology work has established distinct, predictable hormone profiles based on measurable events within the menstrual cycle (MC; menses and ovulation) [1,2]. Specifically, low concentrations of both estradiol and progesterone are present during the first 5 days [1,2]. An isolated peak in estradiol concentration occurs 1-2 days prior to ovulation, and progesterone concentration peaks simultaneous to a smaller surge in estradiol 6-8 days after ovulation [1,2]. Oral contraceptive (OC) use dampens ovarian hormones throughout the month [[1], [2], [3]]. During the placebo phase of OCs, however, endogenous estradiol and progesterone concentrations rise slightly [[1], [2], [3], [4], [5]].

Basic science literature demonstrates an excitatory effect of estradiol [[6], [7], [8], [9]] and inhibitory effect of progesterone [6,8] on the central nervous system. Thus, these hormones have the potential to alter cortical drive and muscle performance. Females after anterior cruciate ligament reconstruction (ACLR) have lower cortical drive to the quadriceps muscle [10] and poorer quadriceps muscle performance than males [[10], [11], [12]]. This is particularly noteworthy as quadriceps muscle performance is related to outcomes after ACLR [[13], [14], [15], [16], [17], [18], [19], [20]]. Greater quadriceps peak torque (PT) is associated with better knee function [[13], [14], [15]], lower reinjury risk [16,17], and better knee joint health [18,19]. Rate of torque development (RTD) is a measure of quadriceps performance that captures speed of muscle contraction [21]. Impairments in the RTD are associated with altered knee biomechanics in running after ACLR [20,22]. A more comprehensive understanding of how estradiol and progesterone influence cortical drive and muscle performance is critical to better understand the sex difference in cortical drive and quadriceps muscle dysfunction after ACLR [10].

There is limited research investigating differences in cortical drive [[23], [24], [25]] or muscle performance [23,24,[26], [27], [28], [29]] across MC phases. Findings across the existing studies vary extensively [[23], [24], [25], [26], [27], [28], [29]]. Some work has reported hormonal influences on these measures [23,24,26,28], while other work reports no effect [23,[25], [26], [27], [28], [29]]. The inconsistent findings among the aforementioned studies may largely be explained by the reliance on cycle day to define MC phase, creating a lack of objectively determined phases [1,2,28]. No studies to date have compared cortical drive or quadriceps performance between naturally menstruating (NM) individuals and OC users or investigated the association between circulating hormones and cortical drive or muscle performance.

The purpose of this study was to first determine the effect of MC phase and OC use on cortical drive and quadriceps performance in uninjured females. We hypothesized lesser cortical drive in NM individuals during the mid-luteal phase than during the early follicular phase but no change in excitability across active and placebo pills for OC users. We also hypothesized no effect of phase or hormone status on quadriceps performance due to the multifactorial central and peripheral mechanisms contributing to quadriceps motor output. The second purpose was to determine the relationship between circulating ovarian hormones and cortical drive. We hypothesized that cortical drive would be positively associated with circulating estradiol and that there would be no significant association between circulating hormones and quadriceps performance.

Materials and methods

Study design

This was a longitudinal cohort study. Participants were recruited from the local community, primarily through the university campus. Inclusion criteria consisted of physically active (level I, II, or III athletes) [17,30] uninjured females aged 18-35 years. Two groups were included: NM individuals (using no hormonal contraceptives for >1 years) and OC users (estrogen and progesterone monophasic, biphasic, or triphasic pill). NM participants tracked their MC (the onset of menses and urinary ovulation tests) for a minimum of 2 cycles prior to data collection (Fig. 1). NM participants with cycle lengths <21 or >35 days during tracking were excluded. Participants using other hormonal contraceptive methods, with medical conditions known to impact circulating ovarian hormones (eg, polycystic ovary syndrome, thyroid disease, primary ovarian insufficiency), and participants who were pregnant (currently or within 1 year) were excluded. Transcranial magnetic stimulation (TMS) exclusion criteria consisted of history of neurologic condition, seizures, severe migraines, concussion within the last 6 months, and metal or other implant present in the head or neck. Those who underwent prior lower extremity surgery were excluded from the study. This study was approved by our institution’s institutional review board, and all participants gave informed consent prior to participation.

Figure 1.

Figure 1

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Menstrual cycle tracking and study design. (A) Representation of menstrual cycle tracking. Day 1 is defined as onset of menses, urinary ovulation testing completed daily starting on day 11 until positive test. (B) Data collection time points. HIGH: high hormone phase (mid-luteal phase and active pill). LOW: low hormone phase (early follicular and placebo pill). NM, naturally menstruating; OC, oral contraceptive.

All participants completed 2 testing time points (Fig. 1). First, during a high hormone phase: NM participants during the mid-luteal phase (6-8 days after ovulation) and OC users during the active phase of their prescription. The second time point was during a low hormone phase: NM participants during the early follicular phase (day 1-5 of the subsequent MC) and OC users during the placebo phase of their prescription. These time points were selected based on the previously published expert recommendation to capture high circulating serum estradiol and progesterone (mid-luteal phase) and low circulating serum estradiol and progesterone (early follicular) among NM participants [2]. OC users completed testing 7-14 days apart to mimic similar time between testing as the NM participants.

Procedures

Serum hormone concentrations

Blood samples were collected at the time of testing by trained phlebotomists and centrifuged. The plasma layer was pipetted into aliquots of 300 μL and stored at −80 °C. Commercially available enzyme-linked immunosorbent assay kits (Eagle Biosciences, Amherst, NH, USA) were used to quantify serum concentrations of estradiol and progesterone [23,31]. All samples were run in duplicate. Mean coefficients of variation across estradiol and progesterone samples were 9.2% and 11.5%, respectively. Hormone concentrations are reported for each time point (high and low hormone) and as the ratio of concentrations for high to low hormone time points to describe change across phases.

Quadriceps muscle performance

Participants completed quadriceps performance testing on an isokinetic dynamometer (HUMAC NORM, CSMi, Stoughton, MA, USA) with torque data sampled at 5000 Hz. Isometric testing was completed in 60° of knee flexion with three submaximal repetitions preceding three maximal voluntary isometric contractions (MVICs), as previously described [10]. Isometric peak torque (PTISOM) was the greatest torque achieved normalized to body mass. The RTD was calculated for the first (rate of torque development from 0 to 100 ms [RTD100]) and second (rate of torque development from 100 to 200 ms [RTD200]) 100 ms from 3 separate ballistic contractions during which participants were provided a visual target at 80% of PTISOM and instructed “hit the target as fast as you can.” The highest value achieved was used for analysis. Isokinetic quadriceps testing was completed at 180°/s, with five familiarization repetitions followed by five maximal effort repetitions during which participants were provided visual feedback and maximal verbal encouragement. Isokinetic peak torque (PTISOK) was the greatest torque achieved normalized to body mass.

Cortical drive

Cortical drive was assessed using TMS (Magstim BiStim, Magstim, West Wales, UK) with participants seated on an isokinetic dynamometer, as described earlier, for MVIC testing. Participants were provided a visual feedback target bar at 5% of their MVIC and instructed to maintain torque within the target for all TMS stimuli. Electromyography (EMG) was used to quantify muscle activity at the vastus medialis based on SENIAM (Surface ElectroMyoGraphy for the Non-Invasive Assessment of Muscles) recommendations [32]. EMG data were sampled at 5000 Hz using MA-300 system (Motion Lab Systems). The “hot spot” was identified as the location of the TMS coil that elicited the largest EMG response at the vastus medialis [10,[33], [34], [35]]. Cortical drive was quantified as corticospinal excitability (CSE) and intracortical excitability. CSE included two measures: the active motor threshold (AMT) and the slope of the stimulus-response curve (SLOPE). AMT was the lowest stimulator output required to obtain peak-to-peak motor-evoked potentials ≥100 μV in 3 of 5 trials [10,[35], [36], [37]]. SLOPE was the slope of the recruitment curve obtained from stimulation at 100%-140% of AMT [10,35]. Intracortical excitability included intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) using paired-pulse TMS with a conditioning (initial, 80% AMT) pulse followed by a test (second, 120% AMT) pulse [33,34]. Interpulse intervals were 15 ms and 3 ms for ICF and SICI, respectively [33,34]. ICF and SICI are quantified as the conditioned response relative to the unconditioned response at 120% AMT (expressed as a percentage of the unconditioned response). Larger values for ICF indicate greater facilitation. Smaller values for SICI indicate greater inhibition.

Statistical analysis

A priori power analysis indicated 17 participants in each group were needed to achieve a statistical power of 0.80 to detect a moderate effect size with a significance of α = 0.05. Due to the exclusion criteria of the study, we accepted the type II error risk of lower statistical power for the exploratory nature of this work.

Independent samples t-tests and Chi-squared tests of independence assessed for differences in demographics (age, height, body mass, and activity level) between OC users and NM participants. We tested for between-limb differences on all cortical drive and quadriceps performance measures using a paired-sample t-test. There were no between-limb differences for any quadriceps performance variables, so the average of the two limbs was used for all subsequent analyses. Linear mixed-effect models were used to determine the status (NM individuals vs OC users) by phase interaction and the main effects of phase and hormone status on all measures of cortical drive, quadriceps performance, and each hormone concentration. Independent samples t-tests compared the ratio of high to low hormone concentrations between groups. Simple-effect post hoc testing with Bonferroni corrections (to control for multiple simple effects comparisons) was used for any significant status by phase interactions.

To determine the association between (1) hormone concentration and cortical drive and (2) hormone concentration and quadriceps performance, we performed Pearson’s correlations to determine associations between hormone concentrations and all cortical and quadriceps variables. We then performed separate multivariate linear regressions using the entire data set (high hormone and low hormone time points for all participants) with 3 independent variables: hormone concentration, a dummy variable for hormone status (1 = OC, 0 = NM), and an interaction term (hormone status∗hormone concentration) to assess the moderation effect of hormone status on the relationship. A moderation effect was deemed meaningful if both the multivariate regression and the interaction term were significant. The alpha value was set a priori to P = .05.

Results

Participants

Twenty-five participants (11 OC users and 14 NM individuals) were screened for eligibility, consented, enrolled in the study, and completed both testing time points. Five NM participants enrolled in the study but did not complete it (1 withdrew due to possible pregnancy, 2 were excluded due to oligomenorrhea identified during tracking, and 2 were lost to follow-up during tracking). Participant demographics are listed in Table 1.

Table 1.

Participant demographics.

NM (n = 14) OC (n = 11) P-value
Age (y) 23.7 ± 2.8 22.3 ± 1.5 .139
Height (cm) 165.1 ± 6.9 162.8 ± 8.2 .453
BMI 23.7 ± 3.7 24.3 ± 3.9 .720
Mass (kg) 64.8 ± 12.0 64.5 ± 13.1 .953
Activity level Level I, 3 Level I, 2 .970
Level II, 4 Level II, 3
Level III, 7 Level III, 6
IKDC 98.8 ± 1.8 99.2 ± 1.6 .573
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BMI, body mass index; NM, naturally menstruating; OC, oral contraceptive; IKDC, International Knee Documentation committee subjective knee form.

Hormone concentration levels

There was a hormone status by phase interaction for progesterone (P < .001; Table 2). Post hoc testing revealed progesterone decreased from the high hormone phase to low hormone phase in NM participants (Bonferroni adjusted P < .004) but not OC users (Bonferroni adjusted P = .084) and was lower in OC users than in NM participants at the high hormone phase (Bonferroni adjusted P < .004). There were no significant main effects (P ≥ .126) or interactions (P = .160) for estradiol. Independent samples t-tests revealed group differences in hormone ratios (high to low time points) between NM and OC users: estradiol (NM individuals: 1.25 ± 0.46, OC users: 0.94 ± 0.18, P = .046) and progesterone (NM individuals: 2.64 ± 0.71, OC users: 0.94 ± 0.44, P < .001).

Table 2.

Serum hormone concentrations.

High hormone Low hormone High/low hormone
Estradiol (pg/mL) NM 194.7 ± 174.8 169.5 ± 197.3 1.25 ± 0.46
OC 136.2 ± 139.2 135.1 ± 128.1 0.94 ± 0.18
Progesterone (ng/mL)a NM 9.77 ± 5.04 1.69 ± 0.88 5.25 ± 2.64
OC 1.89 ± 2.03 2.42 ± 2.16 0.94 ± 0.44
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NM, naturally menstruating; OC, oral contraceptive.

Hormone concentrations are presented as isolated hormone concentrations for each time point and the ratio of hormone concentration at the high relative to low hormone time point.

a

Indicates phase x hormone status interaction P < .01.

MC phase and OC effect on cortical drive and quadriceps performance

There were no significant interactions on any measure of cortical drive (P ≥ .358), and they were removed from their respective models. There were no significant main effects of hormone status or phase for any measure of cortical drive (P ≥ .092, Fig. 2). There was a significant hormone status by phase interaction on the RTD (P = .018). Post hoc testing revealed the RTD100 significantly decreased from high to low hormone phase in NM individuals (Bonferroni adjusted P < .004) but not in OC users (Bonferroni adjusted P = .168). Interactions were nonsignificant for all other quadriceps performance measures (P ≥ .403) and were removed from the respective models. There was a main effect of phase with a greater PTISOM at the low hormone phase (P = .049). There were no significant main effects of hormone status or phase for the RTD200 or PTISOK (P ≥ .156, Table 3).

Figure 2.

Figure 2

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Cortical drive across phases and hormone status. (A) AMT (active motor threshold), (B) SLOPE (slope of the stimulus-response curve), (C) ICF (intracortical facilitation), (D) SICI (short-interval intracortical inhibition). HIGH, high hormone phase (mid-luteal phase and active pill); LOW, low hormone phase (early follicular and placebo pill). NM, naturally menstruating; OC, oral contraceptive.

Table 3.

Quadriceps performance and cortical drive.

High hormone Low hormone Interaction (status by phase) Main effect of hormone status Main effect of phase
PTISOM (Nm/kg) NM 2.7 ± 0.4 2.8 ± 0.4 P = .403 P = .116 P = .049
OC 2.4 ± 0.6 2.5 ± 0.7
PTISOK (Nm/kg) NM 1.3 ± 0.3 1.3 ± 0.3 P = .891 P = .157 P = .637
OC 1.2 ± 0.3 1.2 ± 0.3
RTD100 (Nm/s) NM 942.8 ± 287.2 646.8 ± 195.3 P = .018 P = .080 P < .001
OC 679.1 ± 302.9 566.6 ± 227.3
RTD200 (Nm/s) NM 399.9 ± 151.6 438.5 ± 209.0 P = .663 P = .653 P = .176
OC 436.7 ± 98.1 456.7 ± 138.2
AMT NM 39.0 ± 7.5 37.8 ± 8.0 P = .358 P = .797 P = .847
OC 38.7 ± 7.2 39.5 ± 5.0
SLOPE NM 0.039 ± 0.029 0.033 ± 0.026 P = .718 P = .092 P = .104
OC 0.069 ± 0.058 0.058 ± 0.048
ICF NM 132 ± 42 129 ± 33 P = .452 P = .114 P = .262
OC 161 ± 45 144 ± 39
SICI NM 67 ± 28 68 ± 22 P = .629 P = .428 P = .752
OC 76 ± 25 72 ± 19
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NM, naturally menstruating; OC, oral contraceptive; PTISOM, isometric peak torque; PTISOK, isokinetic peak torque; RTD100, rate of torque development from 0 to 100 ms; RTD200, rate of torque development from 100 to 200 ms; AMT, active motor threshold; SLOPE, slope of the stimulus-response curve; ICF, intracortical facilitation; SICI, short-interval intracortical inhibition.

Association between ovarian hormones, cortical drive, and quadriceps performance

There was a significant negative association between estradiol and SICI for the entire cohort (R = −0.315, P = .026). There was a significant correlation between progesterone and RTD (R = 0.380, P = .006) with a significant moderation effect of hormone status (R2 = 0.244, P = .044, Fig. 3), meaning the relationship differed between NM and OC. There were no other significant associations between any additional cortical drive (P ≥ .243) or quadriceps performance (P ≥ .079) measures and ovarian hormone concentration (Table 4). There were no other significant moderation effects of hormone status on any other relationships between hormones and cortical or quadriceps measures (P ≥ .071).

Figure 3.

Figure 3

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Moderation effect of hormone status on the association between circulating progesterone and rate of torque development. RTD100, rate of torque development from 0 to 100 ms; NM, naturally menstruating; OC, oral contraceptive.

Table 4.

Pearson correlation coefficients for the associations between circulating ovarian hormones, cortical drive, and quadriceps performance.

Estradiol (pg/mL) Progesterone (ng/mL)
AMT (%MSO) −0.049 0.168
SLOPE (mV/%AMT) −0.129 −0.151
ICF (%MEP120) −0.155 −0.056
SICI (%MEP120) −0.315∗ −0.090
PTISOM (Nm/kg) 0.025 0.183
PTISOK (Nm/kg) 0.220 0.251
RTD100 (Nm/s) −0.151 0.380∗∗
RTD200 (Nm/s) 0.086 −0.088
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AMT, active motor threshold; MSO, maximum stimulator output; SLOPE, slope of the stimulus-response curve; ICF, intracortical facilitation; MEP, motor-evoked potential; SICI, short-interval intracortical inhibition; PTISOM, isometric peak torque; PTISOK, isokinetic peak torque; RTD100, rate of torque development from 0 to 100 ms.

∗indicates P < .05, ∗∗indicates P < .01.

Discussion

This study aimed to (1) determine the effect of MC phase and hormonal status on cortical drive and quadriceps performance in uninjured females and (2) determine the relationship between circulating ovarian hormones on cortical drive and quadriceps performance. For the first purpose, we found no significant main effects or interactions on any cortical drive measure, which was contrary to our hypothesis. We found a significant hormone status by phase interaction for quadriceps RTD with a decrease in RTD, or quadriceps contraction speed, among NM participants but no significant change among OC users. We also found a significant main effect of time with higher PT, or quadriceps strength, during the low hormone phase (early follicular phase for NM participants and during the placebo phase for OC users). For the second purpose, we found a significant association between estradiol and SICI (intracortical inhibition) and a significant association between progesterone and RTD, which partially confirmed our hypothesis.

Effect of MC phase and hormone status on cortical drive and quadriceps performance

There were no significant main effects or interactions on any measure of cortical drive. This is partially consistent with one prior study, which identified differences in intracortical inhibition between phases but no differences in CSE [23]. Our findings are consistent with a previous study that found no differences in intracortical inhibition or ICF to hand muscles between the follicular, ovulation, and mid-luteal phases [25]. However, there are key methodological differences between studies. Both prior studies included three time points but defined phases only based on cycle day. In contrast, the current study only included two time points but defined the mid-luteal phase in days relative to confirmed ovulation providing a more precise phase estimate. Based on our findings, MC phase and OC use may not affect cortical drive in uninjured females.

RTD100 decreased from high hormone to low hormone in NM individuals but not in OC users. This suggests the hormonal fluctuations that occur among NM individuals may affect muscle performance. The RTD reflects how quickly the quadriceps muscle contracts and generates torque [21,22]. Specifically, RTD100 reflects the speed of contraction in the initial 100 ms. Differences across phases may have implications for athletes’ performance of high-speed tasks like running [20,22]. No prior studies have investigated differences in RTD across MC phases or hormone status.

PTISOM increased between high (mid-luteal, active pill) and low hormone (early follicular, placebo pill) phases. This increase in maximal strength may be the result of a learning effect, but the magnitude of differences between high and low hormone phases may not be clinically meaningful as they were small and less than the minimal detectable change [38] (PTISOM difference: 0.09 Nm/kg, Cohen’s d = 0.40) [39]. These findings are partially consistent with one prior study that found lower quadriceps strength in the mid-luteal phase than in the late follicular phase [26]; however, the methodology of the prior study (phase definitions, phase of interest, and quadriceps performance measures) differs remarkably from the current study and limits comparison. Our findings are consistent with a systematic review and meta-analysis that found small magnitude differences in general physical performance (a variety of exercise performance testing including strength, functional performance, and endurance) between MC phases [28].

Association between ovarian hormones, cortical drive, and quadriceps performance

Partially consistent with our hypothesis, intracortical inhibition was associated with circulating estradiol concentration. Participants demonstrated lesser inhibition at lower concentrations of estradiol. The direction of the relationship we found is opposite to what we expected. No prior studies have evaluated the relationship between ovarian hormones and cortical drive, but this finding is inconsistent with prior basic science literature that described an overall excitatory effect of estradiol [[6], [7], [8], [9]]. Our study design only included 2 time points targeting a high and a low hormone profile [1,2]. Any excitatory effect of estradiol at the high hormone phase in the current study may have been masked or affected by an inhibitory effect of the simultaneous surge in progesterone. We also did not see the expected decrease in estradiol from high to low hormone phases in our cohort (Table 2), and this may have impacted our findings. We did see a significant difference between NM participants and OC users in the ratio of estradiol concentrations between time points (Table 2). The lack of a difference in estradiol between phases may be due a combination of the small sample size and our selected phases. Hormone expression is highly variable between individuals [1], and we may not have been adequately powered to detect the smaller magnitude difference in estradiol expression between these time points. The individual variability in circulating hormones may require a larger sample to detect differences in estradiol between the early follicular and mid-luteal phases.

Hormone status significantly moderated the relationship between progesterone and speed of contraction. Interestingly, the relationship was positive among NM participants but negative among OC users. This means that at greater concentrations of progesterone NM participants exhibited faster muscle contractions, but OC users exhibited slower muscle contractions. The lack of an isolated high estradiol time point may also contribute to the association. Our high hormone phase captured an expected simultaneous rise of estradiol and surge of progesterone and the potential central nervous system effects may be negated by selecting one phase where both hormone concentrations are high and one phase where both concentrations are low.

The variability of progesterone concentration among NM participants was also greater than among OC users, consistent with established effects of oral contraceptives on circulating ovarian hormones [1,3], which may contribute to the moderation effect. Endogenous ovarian hormones may also have greater impact on the physiological activity than exogenous ovarian hormones when considering the context of previous research that found differences in binding affinity between endogenous and exogenous estradiol [1,40].

Limitations

This was an exploratory study, and the findings should be considered in the context of its limitations. First, we did not capture an isolated high estradiol phase (late follicular). Given the opposite actions of estradiol and progesterone on the central nervous system, cortical drive may differ at this additional time point within the MC. Second, we did not control for specific prescription types in the OC users. This may have limited our findings as different hormonal prescriptions yield different degrees of hormonal response [41]. However, we chose not to control for prescription type in order to bolster our sample size. Third, given the sample size and uneven groups, we may have been underpowered for some of our comparisons and the null findings from our first purpose may be a result of type II error. Surprisingly, despite reportedly roughly half of female athletes using OCs [42], we were unable to recruit as many OC users as NM participants. The stringent exclusion criteria (hormonal and TMS-specific) limited our eligible participant pool and ability to recruit additional OC users. Fourth, we completed testing during the equivalent of one MC. While repeat testing during a subsequent MC would have strengthened our understanding of between-phase differences and consistency of hormone concentrations [43], this was not feasible for the current study.

Conclusion

MC phase and hormone status may affect speed of contraction but not cortical drive among uninjured athletes. This suggests that any influence of ovarian hormones on speed of contraction may be coming from subcortical mechanisms (ie, peripheral nerve or muscle/tendon properties). Effects of ovarian hormones and MC phase on cortical drive and muscle performance should also be further explored in patient populations. The null findings within this study may be due to our small sample size, and we may have been underpowered to detect main effects or interactions. Furthermore, the effects of MC phase and ovarian hormones may differ in patient populations such as those after ACLR where cortical drive and quadriceps performance are known to be altered relative to uninjured individuals.

Author contributions

Anne Leung: Writing – review & editing, Writing – original draft, Visualization, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Elizabeth Wellsandt: Writing – review & editing, Methodology, Formal analysis, Conceptualization. Philip Malloy: Writing – review & editing, Methodology, Formal analysis, Conceptualization. Dustin Grooms: Writing – review & editing, Methodology, Formal analysis, Conceptualization. Ryan Zarzycki: Writing – review & editing, Writing – original draft, Supervision, Resources, Methodology, Conceptualization.

Ethics approval and consent

Complete written informed consent was obtained from the patient or their guardian or legal representative for the publication of this study and accompanying images.

Funding

This work was supported in part by a Promotion of Doctoral Studies Scholarship from the Foundation for Physical Therapy Research.

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We would like to thank Alexa Barnett, Natalee Dragotta, Julia Eckert, Brylie Greene, and Emily Nervegna for their assistance with data collection for this study. We would also like to acknowledge John Hoffman for advising on hormone concentration quantification and Amanda Miller, Kristin Druien, and Theresa Smith for their assistance with blood sample collection.

Footnotes

This article is part of a special issue entitled: The Young Female Athlete published in Journal of the Pediatric Orthopaedic Society of North America.

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