Investigating the Impact of Sex Hormones in Multiple Sclerosis

NCT07081594 | Active Not Recruiting

• 1 other identifier: STU00224323
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Emerging evidence indicates that females with MS experience worsened symptoms during the luteal phase (post ovulation) of the menstrual cycle when progesterone levels rise and estradiol fluctuate. The rapid hormonal swings may disrupt hypothalamic regulation, leading to an increase in body temperature - a well-established trigger for MS symptom exacerbation. These hormonal changes could also affect neuromuscular function, as estradiol and progesterone receptors are present in the nervous system and skeletal muscles. Three critical aspects of motor rehabilitation are corticospinal excitability, motor learning, and fatigability. Previous research indicates that corticospinal excitability and the capacity to learn fine motor tasks fluctuate across menstrual cycles, indicating hormonal influences on neuroplasticity. However, it remains unclear how these hormonal fluctuations specifically affect corticospinal excitability, motor learning, and motor fatigability in females with MS. Understanding these relationships could significantly improve rehabilitation approaches. For example, pre-menopause females with MS may experience a more optimal state for neuroplasticity during the follicular phase of their cycles, therefore providing a potential window for greater rehabilitation efficacy.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Sex hormones; menstrual cycle

Outcome Measures

Primary Outcomes (2)

• Corticospinal excitability

  Measuring the brain to muscle connection using transcranial magnetic stimulation - a non-invasive way to measure brain activity. Peak to Peak amplitude in mV is recorded

  At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

• Blood Draw

  To quantify estradiol and progesterone levels. Normative values of estradiol (E) and progesterone (P) per phase: early follicular (E: 125pmol/L; P: 0.38nmol/L), late follicular (E: 464pmol/L; P: 0.188nmol/L), luteal (E: 412pmol/L; P: 28.8nmol/L)

  At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

Secondary Outcomes (3)

• strength

  At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

• Fatigue

  At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

• Motor Learning

  At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal

Study Arms (1)

Pre-Menopausal Women

Naturally cycling women with multiple sclerosis

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Persons with menstrual cycles and any form of multiple sclerosis

You may qualify if:

• Age ≥18 years
• Diagnosis of relapsing-remitting, primary progressive or secondary progressive MS with no minimum years since diagnosis
• Stable disease modifying therapies for at least 6 months
• Eumenorrheic females

You may not qualify if:

• Another diagnosis (e.g., peripheral neuropathies or orthopedic)
• Pregnancy as confirmed by urine test
• Irregular menstrual cycles
• Diagnosis of premenstrual dysphoric disorder or polycystic ovary syndrome
• Taking antipsychotic medications / does not pass the TMS safety checklist

Sponsors & Collaborators

• Milap Sandhu: lead

Study Sites (1)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

Location

Related Publications (5)

• Christogianni A, O'Garro J, Bibb R, Filtness A, Filingeri D. Heat and cold sensitivity in multiple sclerosis: A patient-centred perspective on triggers, symptoms, and thermal resilience practices. Mult Scler Relat Disord. 2022 Nov;67:104075. doi: 10.1016/j.msard.2022.104075. Epub 2022 Jul 25.

  PMID: 35963205 BACKGROUND

• Karim HT, Huppert TJ, Erickson KI, Wollam ME, Sparto PJ, Sejdic E, VanSwearingen JM. Motor sequence learning-induced neural efficiency in functional brain connectivity. Behav Brain Res. 2017 Feb 15;319:87-95. doi: 10.1016/j.bbr.2016.11.021. Epub 2016 Nov 11.

  PMID: 27845228 BACKGROUND

• Casamento-Moran A, Mooney RA, Chib VS, Celnik PA. Cerebellar Excitability Regulates Physical Fatigue Perception. J Neurosci. 2023 Apr 26;43(17):3094-3106. doi: 10.1523/JNEUROSCI.1406-22.2023. Epub 2023 Mar 13.

  PMID: 36914263 BACKGROUND

• Hackney AC, ed. Sex Hormones, Exercise and Women: Scientific and Clinical Aspects. 1st ed. 2017. Springer International Publishing : Imprint: Springer; 2017. doi:10.1007/978-3-319-44558-81

  BACKGROUND

• Gilli F, DiSano KD, Pachner AR. SeXX Matters in Multiple Sclerosis. Front Neurol. 2020 Jul 3;11:616. doi: 10.3389/fneur.2020.00616. eCollection 2020.

  PMID: 32719651 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Milap Sandhu, PT, PhD

  Shirley Ryan AbilityLab

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: July 23, 2025
• Study Start: August 28, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Following IRB approval, documents will be available
• Access Criteria: These data will be available upon request

Locations

US (1)