Effect of Oestrogen on Musculoskeletal Outcomes

NCT05587920 | Unknown

• 1 other identifier: 1042/MODREC/20
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This cross-sectional comparison and prospective cohort design study will investigate differences in calcium metabolism, biochemical markers of bone and reproductive health, musculoskeletal health, and iron status between women using different hormonal contraceptives (combined oral contraceptive pill (COCP), hormonal implant, hormonal intra-uterine system (IUS), hormonal contraceptive injection, and eumenorrheic non-hormonal contraceptive users). The same outcomes will also be examined across a menstrual cycle in the eumenorrheic non-hormonal contraceptive users. The study will test the following hypotheses: Hormonal contraceptive use

1. 1.Biochemical markers of bone resorption and formation and ratio of urinary 44Ca:42Ca will be higher in the implant and injection groups compared with IUS (which exerts localised effects) and non-HC users (ovulatory phase), and lower in COCP compared with non-HC users;
2. 2.Oestradiol and progesterone will be lower in hormonal contraceptive users compared with non-HC users during the ovulatory phase;
3. 3.Bone macro- and microstructure, muscle strength, and tissue properties are different in hormonal contraceptive users compared with non-HC users;
4. 4.Calcium and bone metabolism, reproductive hormones and musculoskeletal function are different between the pill phase and non-pill phase of COCP use.
5. 5.Calcium and bone metabolism are lower during the ovulatory phase compared with menses, mid follicular and mid luteal phases.
6. 6.Muscle strength and tissue properties are different across the menstrual cycle in non-HC users.

Conditions

Contraception; Estrogen Deficiency; Estrogen Excess

Outcome Measures

Primary Outcomes (1)

• Calcium balance.

  The ratio of the calcium isotopes 44Ca:42Ca in first morning void urine.

  Baseline measurement for long acting reversible contraceptive users. Day 21 and 28 of the pill cycle for the combined oral contraceptive pill users. Menses (day 0), mid-follicular, ovulation, and mid-luteal phase for non-users.

Secondary Outcomes (10)

• Circulating concentrations of reproductive hormones at rest following an overnight fast.

  Baseline measurement for long acting reversible contraceptive users. Day 21 and 28 of the pill cycle for the combined oral contraceptive pill users. Menses (day 0), mid-follicular, ovulation, and mid-luteal phase for non-users.

• Circulating concentrations of metabolic hormones at rest following an overnight fast.

  Baseline measurement for long acting reversible contraceptive users. Day 21 and 28 of the pill cycle for the combined oral contraceptive pill users. Menses (day 0), mid-follicular, ovulation, and mid-luteal phase for non-users.

• Circulating concentrations of bone turnover markers at rest following an overnight fast.

  Baseline measurement for long acting reversible contraceptive users. Day 21 and 28 of the pill cycle for the combined oral contraceptive pill users. Menses (day 0), mid-follicular, ovulation, and mid-luteal phase for non-users.

• Circulating concentrations of markers of resting iron status following an overnight fast.

  Baseline measurement for long acting reversible contraceptive users. Day 21 and 28 of the pill cycle for the combined oral contraceptive pill users. Menses (day 0), mid-follicular, ovulation, and mid-luteal phase for non-users.

• Areal bone mineral density.

  Single measurement at baseline for long acting reversible contraceptive users, day 21 for combined oral contraceptive users and at ovulation for non-users.

Other Outcomes (4)

• Agreement between wearable detection of ovulation and ovulation inferred from luteinising hormone surge tests.

  For one month prior to the start of the study period, and during the entire study period

• Agreement between dual-energy x-ray absorptiometry and Echolight ultrasound bone mineral density.

  Single measurement at baseline for long acting reversible contraceptive users, day 21 for combined oral contraceptive users, and at ovulation for non-users

• Body composition.

  Single measurement at baseline for long acting reversible contraceptive users, day 21 for combined oral contraceptive users, and at ovulation for non-users

Study Arms (5)

Non-hormonal contraceptive users

Women not using any form of hormonal contraceptive.

Combined oral contraceptive pill users

Women using the oral combined oral contraceptive pill.

Hormonal IUS

Women using the hormonal intrauterine system contraceptive.

Hormonal implant

Women using the hormonal contraceptive implant contraceptive.

Hormonal injection

Women using the hormonal injection contraceptive.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy women of reproductive age.

You may qualify if:

• Aged 18-40 years old
• No hormonal contraceptive use (with regular menstrual cycles 24-35 days in length, and have not been taking any hormonal contraceptives for at least 12 months), or;
• Use of the combined oral contraceptive pill containing ≥25 mg ethinyl-oestradiol (EE) and an anti/low androgenic progestin for at least 12 months, or;
• Use of the hormonal coil (IUS) continuously for at least 2 years, or;
• Use of the hormonal implant continuously for at least 2 years, or;
• Use of the hormonalDMPA injection continuously for at least 2 years;
• Weight stable (no change in self-reported body mass ≥ 5% over the previous 3 months);
• BMI between 18 and 30 kg·m2.

You may not qualify if:

• Taking a hormonal contraceptive other than the combined oral contraceptive pill containing ≥25 mg EE and an anti/low androgenic progestin, hormonal coil (IUS), the hormonal contraceptive implant or the DMPA hormonal injection;
• History of DMPA hormonal injection use in those women not currently using the DMPA hormonal injection;
• Diagnosed Premature Ovarian Insufficiency;
• Pregnancy;
• Less than 2 years postpartum;
• Given birth to more than 2 children;
• Evidence of disordered eating (≥ 20 on the EAT-26);
• Any self-diagnosed eating disorder;
• Self-reported change in body mass of ≥ 5% over the previous 3 months;
• Body mass index of \< 18 or \> 30 kg·m2;
• Evidence of menstrual disturbance (oligomenorrhea: \< 9 menstrual cycles in previous 12 months or amenorrhoea: ≤ 3 menstrual cycles in the previous 12 months);
• Habitual smoking (regularly smoking more than 10 cigarettes per day);
• Taking any medications known to affect bone or calcium metabolism (e.g., treatment for thyroid disorders).
• Total 25-hydroxyvitamin D (25(OH)D)level \< 30 nmol/l at baseline, confirmed with a venous blood sample;
• Self-declared history of heart, liver or kidney disease, diabetes, or thyroid disorder;

Sponsors & Collaborators

• Army Health Branch, British Army: lead
• University of East Anglia, Norwich, United Kingdom: collaborator
• Osteolabs, Kiel, Germany: collaborator
• University of Salford, Salford, United Kingdom: collaborator
• University of Southampton, Southampton, United Kingdom: collaborator

Study Sites (1)

Army Health and Performance Laboratory

Camberley, Surrey, GU15 4PQ, United Kingdom

RECRUITING

Related Publications (1)

• Myers SJ, Knight RL, Wardle SL, Waldock KA, O'Leary TJ, Jones RK, Muckelt PE, Eisenhauer A, Tang JC, Fraser WD, Greeves JP. Effect of Menstrual Cycle and Hormonal Contraception on Musculoskeletal Health and Performance: Protocol for a Prospective Cohort Design and Cross-Sectional Comparison. JMIR Res Protoc. 2024 Jul 11;13:e50542. doi: 10.2196/50542.

  PMID: 38990638 DERIVED

Central Study Contacts

Julie P Greeves, PhD

CONTACT

03001597149; julie.greeves143@mod.gov.uk

Rebecca L Double, BSc(Hons)

CONTACT

0300 155 9516; rebecca.double102@mod.gov.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Higher Scientific Officer

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: October 20, 2022
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: April 21, 2023

Record last verified: 2023-04

Locations

GB (1)