Iron and Muscular Damage: FEmale Metabolism and Menstrual Cycle During Exercise

Completed

• Conditions: Regulation of Sex Hormones on Hepcidin; Regulation of Sex Hormones on Muscle Damage; Iron Metabolism Disorders; Iron-deficiency; Inflammation; Exercise Induced Iron-deficiency; Exercise Induced Muscle Damage
• Interventions: Procedure: Interval running protocol / eccentric-based resistance exercise protocol

• Registration Number: NCT04458662
• Lead Sponsor: Universidad Politecnica de Madrid

Brief Summary

This project is an observational controlled randomized counterbalance study. One hundred and three physically active and healthy women were selected to participate in the IronFEMME Study, of which 57 were eumenorrheic, 30 were oral contraceptive users (OCP) and 16 were postmenopausal women. The project consisted on two sections carrying out at the same time: Iron metabolism (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test (8 bouts of 3 min at 85% of the maximal aerobic speed), whereas the study II protocol was based on an eccentric-based resistance exercise protocol (10 sets of 10 repetitions of plate-loaded barbell parallel back squats at 60% of their 1RM with 2 min of rest between sets). In both studies, eumenorrheic participants were evaluated at three specific moments of the menstrual cycle: Early-follicular phase, late-follicular phase and mid-luteal phase; OCP performed the trial at two moments: Withdrawal phase and active pill phase. Lastly, postmenopausal women were tested only once, since their hormonal status does not fluctuate. The three-step method was used to verify the menstrual cycle phase: calendar counting, blood analyses confirmation and urine-based ovulation kits. Blood samples were obtained to measure sexual hormones (e.g., 17β-Estradiol, Progesterone), iron metabolism parameters (e.g., Hepcidin, Iron, Ferritin, Transferrin) and muscle damage related markers (e.g., Creatine Kinase, Myoglobin, Lactate Dehydrogenase).

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-01
• Primary Completion: 2019-03-31
• Study Completion: 2020-06-01
• Study First Submitted: 2020-06-29
• Status Verified: 2020-07
• Study First Submitted QC: 2020-07-02
• Last Update Submitted: 2020-07-02
• Study First Posted: 2020-07-07
• Last Update Posted: 2020-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 103

Inclusion Criteria

Participants were required to meet the following criteria:

• Healthy adult females between 18 and 40 years old for eumerroheic and oral contraceptive groups or under 60 years old for postmenopausal women.
• Presenting with healthy iron parameters (serum ferritin >20μg/l, haemoglobin >115 μg/l and transferrin saturation >16%).
• Performing endurance training between 5 and 12 h per week (study I) or experienced in resistance training performing at least 1 h session two times per week during a minimum of a year (study II).

Exclusion Criteria

The exclusion criteria included:

• Irregular menstrual cycles.
• Any existing disease and/or metabolic or hormonal disorder.
• Any musculoskeletal injury in the last six months prior to the beginning of the project.
• Any surgery interventions (e.g. ovariectomy) or other medical conditions that would be exacerbated by an eccentric resistance exercise protocol.
• Regular use of medication or dietary supplements that could affect the results (e.g. nonsteroidal anti-inflammatory drugs).
• Taking medication that alters vascular function (e.g. tricyclic antidepressants, α-blockers, β-blockers, etc.).
• Pregnancies in the year preceding.
• Smoking.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Eumenorrheic women	Interval running protocol / eccentric-based resistance exercise protocol	The project consisted on two sections carrying out at the same time: Iron physiology (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test. 5 min warm-up at 60% of the vVO2peak followed by 8 bouts of 3 min at 85% of the vVO2peak with 90 secs recovery at 30% of the vVO2peak between bouts. Finally, a 5 min cool down was performed at 30% of the vVO2peak. The study II protocol was based on an eccentric-based resistance exercise protocol consisted on 10 sets of 10 reps of plate-loaded parallel back squats at 60% of their previously calculated 1RM with 2 mins recoveries between sets. In both studies, eumenorrheic participants were evaluated at three specific moments of the menstrual cycle: Early-follicular phase (EFP), late-follicular phase (LFP) and mid-luteal phase (MLP);
Oral contraceptive users	Interval running protocol / eccentric-based resistance exercise protocol	The project consisted on two sections carrying out at the same time: Iron physiology (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test. 5 min warm-up at 60% of the vVO2peak followed by 8 bouts of 3 min at 85% of the vVO2peak with 90 secs recovery at 30% of the vVO2peak between bouts. Finally, a 5 min cool down was performed at 30% of the vVO2peak. The study II protocol was based on an eccentric-based resistance exercise protocol consisted on 10 sets of 10 reps of plate-loaded parallel back squats at 60% of their previously calculated 1RM with 2 mins recoveries between sets. Oral contraceptive users performed the trial at two moments: Withdrawal phase (WP) and active pill phase (APP).
Postmenopausal women	Interval running protocol / eccentric-based resistance exercise protocol	he project consisted on two sections carrying out at the same time: Iron physiology (Study I) and Muscle damage (Study II). For the study I, the exercise protocol consisted on an interval running test. 5 min warm-up at 60% of the vVO2peak followed by 8 bouts of 3 min at 85% of the vVO2peak with 90 secs recovery at 30% of the vVO2peak between bouts. Finally, a 5 min cool down was performed at 30% of the vVO2peak. The study II protocol was based on an eccentric-based resistance exercise protocol consisted on 10 sets of 10 reps of plate-loaded parallel back squats at 60% of their previously calculated 1RM with 2 mins recoveries between sets. Postmenopausal women were tested only once, since their hormonal status does not fluctuate.

Primary Outcome Measures

Name	Time	Method
Hepcidin	24 hours post-exercise	Hepcidin is a protein that in humans is encoded by the HAMP gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals
Creatine kinase	48 hours post-exercise	It is an enzyme that helps regulate the concentration of adenosine triphosphate within a cell. To do so, creatine kinase catalyzes the movement of a phosphate group from ATP to creatine, forming phosphocreatine. This molecules stores the phosphate group in a stable form, acting as an energy reservoir in cells.

Secondary Outcome Measures

Name	Time	Method
CRP	48 hours post-exercise	C-reactive protein
Transferrin	24 hours post-exercise
Iron	24 hours post-exercise
LDH	48 hours post-exercise	Lactate deshidrogenase
Ferritin	24 hours post-exercise
Mioglobin	48 hours post-exercise
TNF-alfa	48 hours post-exercise
Interleukin-6	48 hours post-exercise

Trial Locations

Locations (1)

Laboratorio de Fisiología Del Esfuerzo. Facultad de Ciencias de La Actividad Física Y Del Deporte. Universidad Politécnica de Madrid.; 🇪🇸 Madrid, Spain