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| Name | Class |
|---|---|
| Ministerio de EconomÃa y Competitividad, Spain | OTHER_GOV |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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); |
| |
| 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). |
| |
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interval running protocol / eccentric-based resistance exercise protocol | Procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Iron | pre-exercise | |
| Iron | 0 hours post-exercise | |
| Iron |
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Inclusion Criteria:
Participants were required to meet the following criteria:
Exclusion Criteria:
The exclusion criteria included:
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Physically active and healthy women. Study I, 37 eumenorrheic women (30.0±6.3 yrs; 59.8±15.7 kg; 163.7±6.3 cm): endurance training (ET) experience of 7.7 yrs and training volume of 5.5±0.9 h/week. Study II, 20 eumenorrheic women (28.8±6.2 yrs; 57.5±13.8 kg; 163.9±6.4 cm): strength training (ST) experience of 6.4±4.1 yrs and training volume of 7.5±2.1 h/week. Eumenorrheic women selected to participate in Study I and II were different, whereas oral contraceptive users and postmenopausal women participated in both studies. 30 oral contraceptive users (25.1±4.3 yrs; 56.2±10.9 kg; 163.1±5.5 cm): ET experience of 7.3±5.5 yrs and training volume of 3.4±1.5 h/week; ST experience of 3.1±1.9 yrs and training volume of 2.5±1.4 h/week. 16 postmenopausal women (51.4±3.7 yrs; 56.7±8.3 kg; 161.7±4.9 cm): ET experience of 7.9±3.4 yrs and training volume of 4.1±1.2 h/week; ST experience of 3.1±1.9 yrs and training volume of 1.6±0.9 h/week
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| Name | Affiliation | Role |
|---|---|---|
| Ana Belén Peinado | LFE Research Group. Universidad Politécnica de Madrid | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Laboratorio de FisiologÃa Del Esfuerzo. Facultad de Ciencias de La Actividad FÃsica Y Del Deporte. Universidad Politécnica de Madrid. | Madrid | 28040 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26866603 | Background | 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. | |
| 23041085 | Background | 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. |
| Label | URL |
|---|---|
| IronFEMME project official web page | View source |
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|
| 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 |
| 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 |
| 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 | Lactate deshidrogenase | pre-exercise |
| LDH | Lactate deshidrogenase | 2 hours post-exercise |
| LDH | Lactate deshidrogenase | 24 hours post-exercise |
| LDH | Lactate deshidrogenase | 48 hours post-exercise |
| 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 | C-reactive protein | pre-exercise |
| CRP | C-reactive protein | 0 hours post-exercise |
| CRP | C-reactive protein | 2 hours post-exercise |
| CRP | C-reactive protein | 24 hours post-exercise |
| CRP | C-reactive protein | 48 hours post-exercise |
| 22792339 | Background | 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. |
| 26657863 | Background | 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. |
| 22535765 | Background | 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. |
| 31677121 | Background | 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. |
| 22572041 | Background | 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. |
| 11817996 | Background | 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. |
| 23869062 | Background | 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. |
| 24373771 | Background | 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. |
| 24151587 | Background | 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. |
| 31246715 | Background | 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. |
| 32131554 | Result | 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. |
| 42055105 | Derived | Guisado-Cuadrado I, Romero-Parra N, Bell M, Elliott-Sale KJ, Sale C, Klentrou P, Peinado AB. Resistance and interval running exercise exert differential short-term post-exercise bone metabolic marker responses in postmenopausal. Bone. 2026 Aug;209:117910. doi: 10.1016/j.bone.2026.117910. Epub 2026 Apr 27. |
| 39738864 | Derived | 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. |
| 37161678 | Derived | 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. |
| 36129579 | Derived | 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. |
| ID | Term |
|---|---|
| D018798 | Anemia, Iron-Deficiency |
| D007249 | Inflammation |
| D019189 | Iron Metabolism Disorders |
| D000090463 | Iron Deficiencies |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D000747 | Anemia, Hypochromic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001519 | Behavior |
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