EMRSHN 2: Exploring the Modulatory Role of Sex Hormones Along the Neuromechanical Axis in Females
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 102
- Locations
- 1
- Primary Endpoint
- Change in Spinal Motor Neuron Excitability in Non Oral Contraceptive User
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 39 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Non-Oral Contraceptive (NOC)
Females ages 18-39 years, who are eumenorrheic (regular monthly cycles of 24-35 days) and moderately active. 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, history of disordered eating, of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease), history of or current diabetes, 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.
Oral Contraceptive ( OC)
Females: ages 18-39 years, who are on a stable hormonal contraceptive regimen for 6 months (oral, transdermal or vaginal) and moderately active. 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, history of disordered eating, of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease), history of or current diabetes, started or stopped taking oral contraceptives within the previous 6 months, participate in high impact endurance training (i.e. pre-marathon training, body building), or currently participating in competitive level sports.
Male
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, history of disordered eating, of a connective tissue disorder (Marfan's syndrome, Ehlers-Danlos disease), history of or current diabetes, 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, and medications that lower seizure threshold.
Outcomes
Primary Outcomes
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.
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.
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.
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.
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.
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.
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
- Change in Flexion Reflex Duration in Non Oral Contraceptive User(Follicular, Luteal)
- Change in Flexion Reflex Root Mean Squared Value in Oral Contraceptive User(Active pill, Inactive pill)
- Change in Steadiness of Isometric Force Production at 20% of Maximum Voluntary Contraction in Non Oral Contraceptive User(Follicular, Luteal)
- Change in Flexion Reflex Root Mean Squared Value in Non Oral Contraceptive User(Follicular, Luteal)
- Change in Flexion Reflex Latency in Non Oral Contraceptive User(Follicular, Luteal)
- Change in Flexion Reflex Duration in Oral Contraceptive User(Active pill, Inactive pill)
- Change in Flexion Reflex Latency in Oral Contraceptive User(Active pill, Inactive pill)
- Change in Steadiness of Isometric Force Production at 20% of Maximum Voluntary Contraction in Oral Contraceptive User(Active pill, Inactive pill)
Investigators
Yasin Dhaher
Professor
University of Texas Southwestern Medical Center