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

NCT ID: NCT04458662

Last Updated: 2020-07-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

103 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-01-01

Study Completion Date

2020-06-01

Brief Summary

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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

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Conditions

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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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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);

Interval running protocol / eccentric-based resistance exercise protocol

Intervention Type PROCEDURE

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).

Interval running protocol / eccentric-based resistance exercise protocol

Intervention Type PROCEDURE

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.

Interval running protocol / eccentric-based resistance exercise protocol

Intervention Type PROCEDURE

Interventions

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Interval running protocol / eccentric-based resistance exercise protocol

Intervention Type PROCEDURE

Eligibility Criteria

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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

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Ministerio de Economía y Competitividad, Spain

OTHER_GOV

Sponsor Role collaborator

Universidad Politecnica de Madrid

OTHER

Sponsor Role lead

Responsible Party

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ANA BELEN PEINADO LOZANO

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ana Belén Peinado

Role: STUDY_DIRECTOR

LFE Research Group. Universidad Politécnica de Madrid

Locations

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Laboratorio de Fisiología Del Esfuerzo. Facultad de Ciencias de La Actividad Física Y Del Deporte. Universidad Politécnica de Madrid.

Madrid, , Spain

Site Status

Countries

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Spain

References

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Lehtihet M, Bonde Y, Beckman L, Berinder K, Hoybye C, Rudling M, Sloan JH, Konrad RJ, Angelin B. Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans. PLoS One. 2016 Feb 11;11(2):e0148802. doi: 10.1371/journal.pone.0148802. eCollection 2016.

Reference Type BACKGROUND
PMID: 26866603 (View on PubMed)

Hou Y, Zhang S, Wang L, Li J, Qu G, He J, Rong H, Ji H, Liu S. Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene. 2012 Dec 15;511(2):398-403. doi: 10.1016/j.gene.2012.09.060. Epub 2012 Oct 3.

Reference Type BACKGROUND
PMID: 23041085 (View on PubMed)

Ikeda Y, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Tamaki T. Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes. PLoS One. 2012;7(7):e40465. doi: 10.1371/journal.pone.0040465. Epub 2012 Jul 11.

Reference Type BACKGROUND
PMID: 22792339 (View on PubMed)

Li X, Rhee DK, Malhotra R, Mayeur C, Hurst LA, Ager E, Shelton G, Kramer Y, McCulloh D, Keefe D, Bloch KD, Bloch DB, Peterson RT. Progesterone receptor membrane component-1 regulates hepcidin biosynthesis. J Clin Invest. 2016 Jan;126(1):389-401. doi: 10.1172/JCI83831. Epub 2015 Dec 14.

Reference Type BACKGROUND
PMID: 26657863 (View on PubMed)

Yang Q, Jian J, Katz S, Abramson SB, Huang X. 17beta-Estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site. Endocrinology. 2012 Jul;153(7):3170-8. doi: 10.1210/en.2011-2045. Epub 2012 Apr 25.

Reference Type BACKGROUND
PMID: 22535765 (View on PubMed)

Thompson B, Almarjawi A, Sculley D, Janse de Jonge X. The Effect of the Menstrual Cycle and Oral Contraceptives on Acute Responses and Chronic Adaptations to Resistance Training: A Systematic Review of the Literature. Sports Med. 2020 Jan;50(1):171-185. doi: 10.1007/s40279-019-01219-1.

Reference Type BACKGROUND
PMID: 31677121 (View on PubMed)

McClung JP. Iron status and the female athlete. J Trace Elem Med Biol. 2012 Jun;26(2-3):124-6. doi: 10.1016/j.jtemb.2012.03.006. Epub 2012 May 7.

Reference Type BACKGROUND
PMID: 22572041 (View on PubMed)

Kendall B, Eston R. Exercise-induced muscle damage and the potential protective role of estrogen. Sports Med. 2002;32(2):103-23. doi: 10.2165/00007256-200232020-00003.

Reference Type BACKGROUND
PMID: 11817996 (View on PubMed)

Tiidus PM, Lowe DA, Brown M. Estrogen replacement and skeletal muscle: mechanisms and population health. J Appl Physiol (1985). 2013 Sep 1;115(5):569-78. doi: 10.1152/japplphysiol.00629.2013. Epub 2013 Jul 18.

Reference Type BACKGROUND
PMID: 23869062 (View on PubMed)

Sim M, Dawson B, Landers G, Swinkels DW, Tjalsma H, Yeap BB, Trinder D, Peeling P. Oral contraception does not alter typical post-exercise interleukin-6 and hepcidin levels in females. J Sci Med Sport. 2015 Jan;18(1):8-12. doi: 10.1016/j.jsams.2013.11.008. Epub 2013 Nov 28.

Reference Type BACKGROUND
PMID: 24373771 (View on PubMed)

Sipaviciene S, Daniuseviciute L, Kliziene I, Kamandulis S, Skurvydas A. Effects of estrogen fluctuation during the menstrual cycle on the response to stretch-shortening exercise in females. Biomed Res Int. 2013;2013:243572. doi: 10.1155/2013/243572. Epub 2013 Sep 12.

Reference Type BACKGROUND
PMID: 24151587 (View on PubMed)

Janse DE Jonge X, Thompson B, Han A. Methodological Recommendations for Menstrual Cycle Research in Sports and Exercise. Med Sci Sports Exerc. 2019 Dec;51(12):2610-2617. doi: 10.1249/MSS.0000000000002073.

Reference Type BACKGROUND
PMID: 31246715 (View on PubMed)

Romero-Parra N, Barba-Moreno L, Rael B, Alfaro-Magallanes VM, Cupeiro R, Diaz AE, Calderon FJ, Peinado AB. Influence of the Menstrual Cycle on Blood Markers of Muscle Damage and Inflammation Following Eccentric Exercise. Int J Environ Res Public Health. 2020 Mar 2;17(5):1618. doi: 10.3390/ijerph17051618.

Reference Type RESULT
PMID: 32131554 (View on PubMed)

Guisado-Cuadrado I, Romero-Parra N, Cupeiro R, Elliott-Sale KJ, Sale C, Peinado AB. Effect of eccentric-based resistance exercise on bone (re)modelling markers across the menstrual cycle and oral contraceptive cycle. Eur J Appl Physiol. 2025 May;125(5):1463-1473. doi: 10.1007/s00421-024-05693-y. Epub 2024 Dec 30.

Reference Type DERIVED
PMID: 39738864 (View on PubMed)

Guisado-Cuadrado I, Alfaro-Magallanes VM, Romero-Parra N, Rael B, Guadalupe-Grau A, Peinado AB. Influence of sex hormones status and type of training on regional bone mineral density in exercising females. Eur J Sport Sci. 2023 Nov;23(11):2139-2147. doi: 10.1080/17461391.2023.2211947. Epub 2023 May 17.

Reference Type DERIVED
PMID: 37161678 (View on PubMed)

Alfaro-Magallanes VM, Barba-Moreno L, Romero-Parra N, Rael B, Benito PJ, Swinkels DW, Laarakkers CM, Diaz AE, Peinado AB; IronFEMME Study Group. Menstrual cycle affects iron homeostasis and hepcidin following interval running exercise in endurance-trained women. Eur J Appl Physiol. 2022 Dec;122(12):2683-2694. doi: 10.1007/s00421-022-05048-5. Epub 2022 Sep 21.

Reference Type DERIVED
PMID: 36129579 (View on PubMed)

Related Links

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https://ironfemme.com

IronFEMME project official web page

Other Identifiers

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DEP2016-75387-P

Identifier Type: -

Identifier Source: org_study_id

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