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

Inflammation Clinical Trial

— IronFEMME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04458662
• Other study ID #: DEP2016-75387-P
• Status: Completed
• Start date: January 1, 2017
• Est. completion date: June 1, 2020

Study information

• Verified date: July 2020
• Source: Universidad Politecnica de Madrid
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: June 1, 2020
• Est. primary completion date: March 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

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, a-blockers, ß-blockers, etc.).

• Pregnancies in the year preceding.

• Smoking.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Exercise Induced Iron-deficiency
• Exercise Induced Muscle Damage
• Inflammation
• Iron Metabolism Disorders
• Iron-deficiency
• Metabolic Diseases
• Regulation of Sex Hormones on Hepcidin
• Regulation of Sex Hormones on Muscle Damage

Intervention

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

Locations

Country	Name	City	State
Spain	Laboratorio de Fisiología Del Esfuerzo. Facultad de Ciencias de La Actividad Física Y Del Deporte. Universidad Politécnica de Madrid.	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Politecnica de Madrid	Ministerio de Economía y Competitividad, Spain

Country where clinical trial is conducted

Spain, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. Review. — View Citation

Kendall B, Eston R. Exercise-induced muscle damage and the potential protective role of estrogen. Sports Med. 2002;32(2):103-23. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Romero-Parra N, Barba-Moreno L, Rael B, Alfaro-Magallanes VM, Cupeiro R, Díaz ÁE, Calderón 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. 2 — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Yang Q, Jian J, Katz S, Abramson SB, Huang X. 17ß-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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepcidin	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	pre-exercise
Primary	Hepcidin	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	0 hours post-exercise
Primary	Hepcidin	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	3 hours post-exercise
Primary	Hepcidin	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	24 hours post-exercise
Primary	Creatine kinase	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.	pre-exercise
Primary	Creatine kinase	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.	2 hours post-exercise
Primary	Creatine kinase	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.	24 hours post-exercise
Primary	Creatine kinase	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.	48 hours post-exercise
Secondary	Iron		pre-exercise
Secondary	Iron		0 hours post-exercise
Secondary	Iron		3 hours post-exercise
Secondary	Iron		24 hours post-exercise
Secondary	Transferrin		pre-exercise
Secondary	Transferrin		0 hours post-exercise
Secondary	Transferrin		3 hours post-exercise
Secondary	Transferrin		24 hours post-exercise
Secondary	Ferritin		pre-exercise
Secondary	Ferritin		0 hours post-exercise
Secondary	Ferritin		3 hours post-exercise
Secondary	Ferritin		24 hours post-exercise
Secondary	Mioglobin		pre-exercise
Secondary	Mioglobin		2 hours post-exercise
Secondary	Mioglobin		24 hours post-exercise
Secondary	Mioglobin		48 hours post-exercise
Secondary	LDH	Lactate deshidrogenase	pre-exercise
Secondary	LDH	Lactate deshidrogenase	2 hours post-exercise
Secondary	LDH	Lactate deshidrogenase	24 hours post-exercise
Secondary	LDH	Lactate deshidrogenase	48 hours post-exercise
Secondary	TNF-alfa		pre-exercise
Secondary	TNF-alfa		2 hours post-exercise
Secondary	TNF-alfa		24 hours post-exercise
Secondary	TNF-alfa		48 hours post-exercise
Secondary	Interleukin-6		pre-exercise
Secondary	Interleukin-6		0 hours post-exercise
Secondary	Interleukin-6		2 hours post-exercise
Secondary	Interleukin-6		24 hours post-exercise
Secondary	Interleukin-6		48 hours post-exercise
Secondary	CRP	C-reactive protein	pre-exercise
Secondary	CRP	C-reactive protein	0 hours post-exercise
Secondary	CRP	C-reactive protein	2 hours post-exercise
Secondary	CRP	C-reactive protein	24 hours post-exercise
Secondary	CRP	C-reactive protein	48 hours post-exercise

External Links

•   IronFEMME project official web page