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

Sponsor

Universidad Politecnica de Madrid (Other)

Overall Status

Completed

CT.gov ID

NCT04458662

Collaborator

Ministerio de Economía y Competitividad, Spain (Other)

103

Enrollment

Location

Actual Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Iron-deficiency Inflammation Exercise Induced Iron-deficiency Exercise Induced Muscle Damage Regulation of Sex Hormones on Hepcidin Regulation of Sex Hormones on Muscle Damage Iron Metabolism Disorders	Procedure: Interval running protocol / eccentric-based resistance exercise protocol

Study Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

103 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

Jan 1, 2017

Actual Primary Completion Date :

Mar 31, 2019

Actual Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Eumenorrheic women 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);	Procedure: Interval running protocol / eccentric-based resistance exercise protocol
Oral contraceptive users 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).	Procedure: Interval running protocol / eccentric-based resistance exercise protocol
Postmenopausal women 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.	Procedure: Interval running protocol / eccentric-based resistance exercise protocol

Arm

Intervention/Treatment

Eumenorrheic women

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);

Procedure: Interval running protocol / eccentric-based resistance exercise protocol

Oral contraceptive users

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).

Procedure: Interval running protocol / eccentric-based resistance exercise protocol

Postmenopausal women

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.

Procedure: Interval running protocol / eccentric-based resistance exercise protocol

Outcome Measures

Primary Outcome Measures

Hepcidin [pre-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
Hepcidin [0 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
Hepcidin [3 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
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 [pre-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.
Creatine kinase [2 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.
Creatine kinase [24 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.
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

Iron [pre-exercise]
Iron [0 hours post-exercise]
Iron [3 hours post-exercise]
Iron [24 hours post-exercise]
Transferrin [pre-exercise]
Transferrin [0 hours post-exercise]
Transferrin [3 hours post-exercise]
Transferrin [24 hours post-exercise]
Ferritin [pre-exercise]
Ferritin [0 hours post-exercise]
Ferritin [3 hours post-exercise]
Ferritin [24 hours post-exercise]
Mioglobin [pre-exercise]
Mioglobin [2 hours post-exercise]
Mioglobin [24 hours post-exercise]
Mioglobin [48 hours post-exercise]
LDH [pre-exercise]
Lactate deshidrogenase
LDH [2 hours post-exercise]
Lactate deshidrogenase
LDH [24 hours post-exercise]
Lactate deshidrogenase
LDH [48 hours post-exercise]
Lactate deshidrogenase
TNF-alfa [pre-exercise]
TNF-alfa [2 hours post-exercise]
TNF-alfa [24 hours post-exercise]
TNF-alfa [48 hours post-exercise]
Interleukin-6 [pre-exercise]
Interleukin-6 [0 hours post-exercise]
Interleukin-6 [2 hours post-exercise]
Interleukin-6 [24 hours post-exercise]
Interleukin-6 [48 hours post-exercise]
CRP [pre-exercise]
C-reactive protein
CRP [0 hours post-exercise]
C-reactive protein
CRP [2 hours post-exercise]
C-reactive protein
CRP [24 hours post-exercise]
C-reactive protein
CRP [48 hours post-exercise]
C-reactive protein

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Laboratorio de Fisiología Del Esfuerzo. Facultad de Ciencias de La Actividad Física Y Del Deporte. Universidad Politécnica de Madrid.	Madrid		Spain	28040