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Completed

NCT Number: NCT03947684

Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females

The goal of this project is to test our central hypothesis that changes in sex hormone concentration result in changes to the basic elements of motor control - at multiple levels, from the musculotendinous unit to motor control circuitry. Under Aim 1 the investigator will determine the influence of sex hormone fluctuations on the muscle stretch reflex during active and passive states, and the time lag between hormone concentration changes and the reflex response. The investigator will use a technically simple assessment that could be implemented in the field. Under Aim 2 the investigator will determine the influence of sex hormone fluctuations on spinal motor neuron excitability using H-reflex as a probe and the simultaneous change in the muscle mechanics using muscle twitch response. Aims 1 & 2 will include a focus on the differential role of oral contraceptives. In Aim 3 the investigator will use paired-pulse transcranial magnetic stimulation during active contraction to determine the influence of sex hormone fluctuation.

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Key information

Conditions

Role of Sex Hormones Along the Neuromechanical Axis

Age range

18 year–39 year

Sex eligibility

All sexes

Study type

Observational

Primary location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Females: ages 18-39 years, who are eumenorrheic (regular monthly cycles of 24-35 days) or on a stable hormonal contraceptive regimen for 6 months (oral, transdermal or vaginal), no history of pregnancy, moderately active (less than 7 hours of vigorous physical activity per week)
  • Males: Ages 18-39

Exclusion criteria

  • History of musculoskeletal or orthopedic injury of the spine, hip, knee, ankle or foot, history of neurological injury of the peripheral or central nervous system, current smoker, history of disordered eating, history of stress fracture in the lower limb, history of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease).
  • For female participants only: Point of care screening for anemia will be completed, and individuals with hemoglobin levels <11.6 g/dl will be excluded from participating in the study.
  • Specific exclusion criteria for TMS (male and female): pacemaker, metal implants in the head region, history of epilepsy or seizures, skull fractures or skull deficits, concussion within the last 6 months, unexplained recurring headaches, medications that lower seizure threshold, and pregnancy.
  • Additional exclusion criteria for female participants: History of menstrual dysfunction (primary or secondary amenorrhea, oligomenorrhea, anovulatory cycles, polycystic ovarian disease), current or past pregnancy, started or stopped taking oral contraceptives within the previous 6 months, exercise vigorously more than 7 hours per week or currently participating in competitive level sports. The reason for excluding highly active or competitive athletes is due to the high rate of undiagnosed menstrual dysfunction in females of this population.
  • This study will not include: adults unable to consent, Individuals who are not yet adults (infants, children, teenagers), pregnant women or prisoners.

Treatment and study plan

Primary outcomes

  1. Changes in Short-interval Intracortical Inhibition (SICI) During the Follicular Phase

    Time frame: day 1 menses up to day with highest estradiol concentration

    The conditioned motor evoked potential (MEP) at each inter-stimulus interval (ISI) was normalized to MEP obtained from unconditioned stimulation. Change was evaluated by regressing the normalized conditioned motor evoked potential amplitude at each ISI with estradiol concentration. Average and standard deviation for each ISI reported.

  2. Change in Stretch Reflex at Relaxed State

    Time frame: Follicular, Luteal

    Muscle stretch reflex (MSR) was calculated by dividing the root mean squared (RMS) value of the electromyogram (EMG) response with the RMS of the muscle's EMG during maximal voluntary contraction and the force of the tapper used to elicit the reflex. Change was evaluated by regressing the ratio simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. Average and standard deviation for each menstrual phase is reported.

  3. Change in Spinal Motor Neuron Excitability in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    The spinal motor neuron excitability was measured by calculating the ratio between the maximum peak-to-peak value of H reflex and the maximum peak-to-peak value of M wave. Change was evaluated by regressing the ratio simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. Average and standard deviation for each menstrual phase is reported.

  4. Normalized Conditioned Motor Evoked Potential in Male and Female

    Time frame: menses period for female, day 1 for male

    The conditioned motor evoked potential (MEP) at each inter-stimulus interval (ISI) was normalized to MEP obtained from unconditioned stimulation. The difference between male and female groups was evaluated using a 2 (male vs. female) x 7 (ISI) repeated measures ANOVA. Average and standard deviation for each ISI reported.

  5. Change in Spinal Motor Neuron Excitability in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    The spinal motor neuron excitability was measured by calculating the ratio between the maximum peak-to-peak value of H reflex and the maximum peak-to-peak value of M wave. Change was evaluated by regressing the ratio simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. Average and standard deviation for active and inactive pill phase are reported.

  6. Changes in Intracortical Facilitation (ICF) During the Follicular Phase

    Time frame: day 1 menses up to day with highest estradiol concentration

    The conditioned motor evoked potential (MEP) at each inter-stimulus interval (ISI) was normalized to MEP obtained from unconditioned stimulation. Change was evaluated by regressing the normalized conditioned motor evoked potential amplitude at each ISI with estradiol concentration. Average and standard deviation for each ISI reported.

  7. Change in Stretch Reflex at Active State

    Time frame: Follicular, Luteal

    Muscle stretch reflex (MSR) was calculated by dividing the root mean squared (RMS) value of the electromyogram (EMG) response with the RMS of the muscle's EMG during maximal voluntary contraction and the force of the tapper used to elicit the reflex. Change was evaluated by regressing the ratio simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. Average and standard deviation for each menstrual phase is reported.

Secondary outcomes

  1. Change in Steadiness of Isometric Force Production at 20% of Maximum Voluntary Contraction in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    Steadiness of the exerted force is quantified using coefficient of variation. Change was evaluated by regressing the steadiness simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  2. Change in Flexion Reflex Root Mean Squared Value in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    The root mean squared (RMS) value were calculated and averaged for each testing visit. Change was evaluated by regressing the RMS simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  3. Change in Flexion Reflex Duration in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    The duration were calculated and averaged for each testing visit. Change was evaluated by regressing the duration simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  4. Change in Flexion Reflex Latency in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    The latency measured from the onset of the stimulus were calculated and averaged for each testing visit. Change was evaluated by regressing the latency simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  5. Change in Flexion Reflex Root Mean Squared Value in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    The root mean squared (RMS) value were calculated and averaged for each testing visit. Change was evaluated by regressing the RMS simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

  6. Change in Flexion Reflex Duration in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    The duration were calculated and averaged for each testing visit. Change was evaluated by regressing the duration simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

  7. Change in Flexion Reflex Latency in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    The latency measured from the onset of the stimulus were calculated and averaged for each testing visit. Change was evaluated by regressing the latency simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

  8. Change in Steadiness of Isometric Force Production at 20% of Maximum Voluntary Contraction in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    Steadiness of the exerted force is quantified using coefficient of variation. Change was evaluated by regressing the steadiness simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

Other outcomes

  1. Change in Muscle Twitch Peak Torque in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    Change was evaluated by regressing the peak torque simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  2. Number of Positive Ovulation

    Time frame: Follicular

    Urinary ovulation kits is used to verify the ovulatory cycles and identify the approximate day of ovulation of the NOC group.

  3. Change in Muscle Twitch Time to Peak Torque in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    Change was evaluated by regressing the time to peak torque simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  4. Change in Muscle Twitch Half Relaxation Time in Non Oral Contraceptive User

    Time frame: Follicular, Luteal

    Change was evaluated by regressing the half relaxation time simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) follicular phase, and (2) luteal phase. Average and standard deviation for each phase is reported.

  5. Change in Muscle Twitch Peak Torque in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    Change was evaluated by regressing the peak torque simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

  6. Change in Muscle Twitch Time to Peak Torque in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    Change was evaluated by regressing the time to peak torque simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

  7. Change in Muscle Twitch Half Relaxation Time in Oral Contraceptive User

    Time frame: Active pill, Inactive pill

    Change was evaluated by regressing the half relaxation time simultaneously on estradiol and progesterone concentrations, and estradiol x progesterone interaction. The analyses was performed during (1) active pill, and (2) inactive pill. Average and standard deviation for each phase is reported.

Sponsors and collaborators

Lead sponsor

University of Texas Southwestern Medical Center

Other

Collaborators

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Registry information

Official study title

EMRSHN 2: Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females

Acronym: EMRSHN

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
May 13, 2019
Registry last updated
Feb 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.