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Completed

NCT Number: NCT07322874

Menstrual Cycle and Exercise-induced Muscle Damage

The aim of the study is to investigate the effect of the different menstrual cycle phases on the recovery from exercise-induced muscle injury in eumenorrheic women. For this purpose, in a cross-over, randomized study, at least 10 healthy eumenorrheic women aged 18-35 years will participate. In a random order, the participants will perform 45 min downhill (-15% slope) running on a treadmill at 70% HRmax followed by a maximal time-trial (95% HRmax) to exhaustion: i) during the follicular phase and ii) during the luteal phase. Before the exercise protocol, as well as at 24 h, 48 h and 72 h following exercise, complete blood count, delayed onset of muscle soreness (DOMS), creatine kinase activity, countermovement jump, isometric, concentric and eccentric strength of knee extensors and knee flexors, will be assessed. In addition, lactic acid concentration will be assessed before and immediately following exercise, and DOMS will be assessed immediately after the end of exercise. Following a washout period of ≥28 days (depending on the length of the menstrual cycle), participants will repeat the exact same procedure for the remaining phase of the menstrual cycle.

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Key information

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Department of Physical Education and Sport Science, University of Thessaly

Trikala, Thessaly, 42100, Greece

About this study

Research in the field of athletic training and rehabilitation, has traditionally focused on men, ignoring the physiological differences between sexes that may significantly affect athletic performance and recovery following exercise-induced muscle damage (EIMD). According to recent reviews of research in sports and exercise medicine, female representation is particularly limited, with only 4% - 13% of studies including women [1]. However, the number of females' participation in regular exercise and sports constantly increases, therefore it is imperative to define EIMD in women.

Except for being limited, most of the existing studies in women have been conducted during the early follicular phase of the cycle, when estrogen and progesterone levels are low, so that women's hormonal profile resembles that of men [2], in order to avoid any fluctuations [3]. However, this approach limits our understanding of the effects of the other phases of the cycle, such as the luteal phase, on performance and exercise-induced inflammation, and thus on women's ability to train and perform.

Although limited, some data suggest the influence of different phases of the menstrual cycle on both performance and exercise-induced muscle injury. For example, women's thermoregulatory levels are higher during the luteal phase of the cycle, which may affect their cardiovascular performance and endurance [4]. Similar data suggest that hormonal fluctuations may also affect recovery from EIMD [5]. Indicatively, the concentration of CK and IL-6 24 h and 72 h following 90 min of continuous running at 70% of VO2max was higher during the follicular phase [6].

Considering the above, research regarding the effect of the different phases of the menstrual cycle on performance and EIMD, it is crucial for the effective design of individualized training programs depending on the phase of the menstrual cycle, to improve performance and avoid injuries in women.

The aim of the study is to investigate the effect of the different menstrual cycle phases on the recovery from EIMD in eumenorrheic women.

According to an initial power analysis performed (probability error: 0.05, power: 0.80), a number of 8-10 individuals is required in order to identify statistically significant differences. Therefore, at least 10 participants will be included in the present study.

The design of the present study is cross-over, randomized and will be conducted in two cycles. The participants, after being informed about the study, as well as the benefits and potential risks, will sign an informed consent for participation in the study. Before the initiation of the data collection, familiarization of the participants with the assessment tests and the exercise protocol at low intensity, will precede. Also, the participants will provide a 7-days diet recall before their participation in the first experimental condition. Subsequently, baseline measurements will be performed at the Biochemistry, Physiology and Exercise Nutrition Laboratory (SmArT Lab), Department of Physical Education and Sports, University of Thessaly: anthropometric characteristics (body height, body mass, body mass index), body composition (body fat percentage, lean body mass, fat mass, bone density), aerobic capacity (VO2max). Subsequently, in a random order, the participants will perform 45 min of submaximal (at 70% HRmax) downhill (-15%) running on a treadmill followed by a maximal (95% HRmax) time-trial to exhaustion: i) during the follicular phase and ii) during the luteal phase. The randomization of the menstrual cycle phases will be done by a random integer sets generator, available online (Random.org). Before the exercise protocol, as well as 24 h, 48 h and 72 h following exercise, complete blood count (CBC), exercise-induced muscle injury [delayed onset muscle soreness (DOMS), creatine kinase (CK) activity] and muscle performance [(countermovement jump (CMJ), isometric, concentric and eccentric strength of knee extensors and knee flexors)] will be assessed. In addition, metabolism (lactic acid) will be assessed before and immediately following exercise, and DOMS will be assessed immediately after the end of exercise. Following a washout period of ≥28 days (depending on the length of the menstrual cycle), participants will repeat the exact same procedure for the remaining phase of the menstrual cycle.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Physically active subjects (VO2max ≥35ml/kg/min)
  • Absence of musculoskeletal injury (≥6 months)
  • Abstinence from the use of ergogenic supplements (≥1 month)
  • Abstinence from anti-inflammatory drugs (≥1 month)
  • Abstinence from participating in exercise with eccentric content for at least 7 days before exercise
  • Abstinence from alcohol and energy drinks before exercise

Exclusion criteria

  • Recent history of musculoskeletal injury (<6 months)
  • Use of ergogenic performance supplements (<1 month)
  • Taking anti-inflammatory drugs (<1 month)
  • Participation in exercise with eccentric content in the previous 7 days before exercise
  • Consumption of alcohol and energy drinks before exercise

Treatment and study plan

Exercise during follicular phase

Other

The participants will perform downhill running (-15% slope) on a treadmill at 70% of HRmax followed by running on a horizontal level (0% slope) at 95% HRmax until exhaustion, during the follicular phase

Exercise during luteal phase

Other

The participants will perform downhill running (-15% slope) on a treadmill at 70% of HRmax followed by running on a horizontal level (0% slope) at 95% HRmax until exhaustion, during the luteal phase

Primary outcomes

  1. Changes in Creatine kinase (CK) activity

    Time frame: At baseline (pre), post-, 24 hours post-, 48 hours post-, 72 hours post-trial

    CK activity will be measured in plasma using a Clinical Chemistry Analyzer with commercially available kits.

  2. Changes in delayed onset of muscle soreness (DOMS)

    Time frame: At baseline (pre), post-, 24 hours post-, 48 hours post-, 72 hours post-tria

    DOMS of knee extensors, knee flexors, gluteal and gastrocnemius muscles of both lower extremities will be measured during palpation of the muscle belly and the distal region after performing three repetitions of a full squat.

  3. Changes in blood lactate concentration

    Time frame: At baseline (pre), 4 minutes post-exercise

    Lactate concentration will be measured in capillary blood with a hand-portable analyzer

  4. Changes in countermovement jump (CMJ) height

    Time frame: At baseline (pre), 24 hours post-, 48 hours post-, 72 hours post-exercise

    CMJ height will be measured with an optical system. Participants will perform 3 maximal CMJ jumps and the best effort will be recorded

  5. Changes in isokinetic strength of knee extensors (KE) and knee flexors (KF)

    Time frame: At baseline (pre), 24 hours post-, 48 hours post-, 72 hours post-exercise

    Isometric, concentric and eccentric peak torque of the KE and KF of both limbs will be assessed on an isokinetic dynamometer

  6. Changes in complete blood count (CBC)

    Time frame: At baseline (pre), 24 hours post-, 48 hours post-, 72 hours post-exercise

    CBC (white blood cells, erythrocytes, platelets) will be measured in an hematological analyzer with commercially available reagents

Secondary outcomes

  1. Differences in Estradiol concentration between trials

    Time frame: At late-follicular and mid-luteal phase (according to each participant's menstrual cycle length), before exercise

    Estradiol concentration will be measured in an automated analyzer with commercially available kits

  2. Differences in Progesterone concentration between trials

    Time frame: At late-follicular and mid-luteal phase (according to each participant's menstrual cycle length), before exercise

    Progesterone concentration will be measured in an automated analyzer with commercially available kits

  3. Body weight

    Time frame: At late-follicular and mid-luteal phase (according to each participant's menstrual cycle length), before exercise

    Body weight will be measured on a beam balance with stadiometer

  4. Body height

    Time frame: At late-follicular and mid-luteal phase (according to each participant's menstrual cycle length), before exercise

    Body height will be measured on a beam balance with stadiometer

  5. Body mass index (BMI)

    Time frame: At late-follicular and mid-luteal phase (according to each participant's menstrual cycle length), before exercise

    BMI will be calculated from the ratio of body mass/ body height squared

  6. Body fat

    Time frame: At late-follicular and mid-luteal phase (according to each participant's menstrual cycle length), before exercise

    Body fat will be measured via bioelectrical impedance

  7. Dietary intake

    Time frame: At baseline

    Dietary intake will be assessed using 7-day diet recalls

Sponsors and collaborators

Lead sponsor

Chariklia K. Deli

Other

Registry information

Official study title

The Effect of Menstrual Cycle on Exercise-induced Muscle Damage

Acronym: MC-EIMD

Important dates

Study start
2025
Primary completion
2025
Study completion
2025
First posted
Jan 7, 2026
Registry last updated
Feb 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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