Effects of the Menstrual Cycle on Triceps Surae Properties in Women

Effects of Menstrual Cycle Phases on Plantar Flexor Neuromechanical Properties and Achilles Tendon Mechanical Properties of Eumenorrheic Women and Hormonal Contraception Users

The menstrual cycle is an important biological rhythm, whereby large cyclic fluctuations in endogenous sex hormones, such as estrogen and progesterone, are observed, which can affect performance. Evidence shows that endogenous and exogenous changes in hormone concentrations during the menstrual cycle exert many effects on the nervous and endocrine systems, in addition to the connective tissue, with consequences for the movement system. Pre-clinical studies (i.e., in animal models) show an estrogen association with the structural and mechanical properties of tendons and ligaments. Several elegant studies performed with female participants have tried to establish the mechanism underlying the effect of estrogen on collagen synthesis and its effects on exercise and functionality. Their findings suggest that the tendon properties may be affected when exposed to varying concentrations of estrogen. The largest tendon in humans, the Achilles tendon, has a direct role in functional capacity, activities of daily living, and locomotion. Studies show that the triceps surae's structural and mechanical properties may change throughout the menstrual cycle, and that these changes are related to endogenous and exogenous fluctuations in estrogen and progesterone. Musculotendinous stiffness, which is dependent on the collagen content, has been seen to vary considerably over the course of the menstrual cycle. In addition, it has been reported that females who have been taking the contraceptive pill for at least a year demonstrate lower levels of tendon strain compared to non-pill taking females, indicating a possible influence of hormonal state on tendon mechanical properties. However, the different experimental designs, the varied approaches to the evaluations and the lack of studies with high methodological quality limit our understanding of the effects of the different phases of the menstrual cycle on the triceps surae's neuromechanical properties. The aim of this observational study will be to investigate whether the morphological, mechanical (active and passive), material, and functional properties of the plantar flexor muscles and of the Achilles tendon, as well as functional parameters, change during voluntary contractions throughout the phases of the menstrual cycle in eumenorrheic women and in users of hormonal contraception. Understanding the acute effects of these properties in eumenorrheic women and users of hormonal contraception is essential so that we can adequately plan interventions and prescriptions of physical exercise and rehabilitation aimed for women.

Study Overview

• Status: Recruiting
• Conditions: Menstrual Cycle; Achilles Tendon
• Intervention / Treatment: Other: Evaluations of the mechanical properties of the achilles tendon in different phases of the menstrual cycle

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Marco Vaz; Phone Number: 5551993851188; Email: marco.vaz@ufrgs.br

Study Locations

• Brazil
  • Porto Alegre, Brazil
    • Recruiting
    • Marco Aurélio Vaz
    • Contact: Marco VAZ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Over the last three decades, there has been a rise in the number of women participating in exercise, from physical activity to elite sports. However, the number of studies regarding female participants' performance is still small compared to male participants. The menstrual cycle is an important biological rhythm, whereby large cyclic fluctuations in endogenous sex hormones, such as estrogen and progesterone, are observed, which can affect performance.

Description

Inclusion Criteria:

• Inclusion criteria for the group of eumenorrheic women

  • Being eumenorrheic with a regular menstrual cycle lasting between 21 and 35 days during the last 6 months prior to study participation.
  • Body Mass Index between 20 and 25 kg/m2.
  • Normal ankle function and range of motion.
  • Do not use hormonal contraception of any kind or supplements hormones for at least the 6 months prior to the study.
  • No complaints of pain or history of lower limb injury.
  • In view of the COVID-19 pandemic, have completed vaccination will be used as an inclusion criteria.
  • For the physically active group, practice regular physical exercise at least 3 times a week for the past 6 months.
  • For the sedentary group, not practicing regular physical exercise in the last 6 months.

Inclusion criteria for the group users of hormonal oral contraception:

• Body Mass Index between 20 and 25 kg/m2.
• Normal ankle function and range of motion.
• Make use of any method of oral hormonal contraception (compressed).
• Make use of combined oral hormonal contraception with estrogen and progesterone (ethinylestradiol + Drospirenone) for at least 6 months before participating in the study.
• Do not use other hormone supplements for at least 6 months prior to the study.
• No complaints of pain or presence of pathologies in the lower limb
• In view of the COVID-19 pandemic, have completed vaccination will be used as an inclusion criteria.
• For the physically active group, practice regular physical exercise at least 3 times a week for the past 6 months.
• For the sedentary group, not practicing regular physical exercise in the last 6 months

Exclusion Criteria:

Exclusion Criteria for eumenorrheic and contraception hormonal groups:

Health problems - contraindication to maximal effort exercise. Additionally, the following subjects will be excluded:

• Women who have anovulatory cycles or phase lutea deficiency.
• Women in early menopause.
• Pregnant or lactating women.
• Women with oligomenorrhea (menstrual cycles longer than 35 days, or delay of menstruation for the same period).
• Women with hypothalamic amenorrhea.
• Female smokers.
• Women with metabolic syndrome.
• For women using hormonal contraceptives, women who use adhesive, injectable, intrauterine devices, implants, vaginal rings, as well as progesterone-only CH methods.
• Does not meet the inclusion criteria.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Physically active eumenorrheic women with regular menstrual cycle; Women who practice physical exercise and have regular menstruation ranging from 25 to 38 days.	Other: Evaluations of the mechanical properties of the achilles tendon in different phases of the menstrual cycle; Monitoring assessments to verify the effect of different phases of the menstrual cycle on the neuromechanical properties of the Achilles tendon.
Sedentary eumenorrheic women with regular menstrual cycle; Women who do not practice physical exercise and have regular menstruation ranging from 25 to 38 days.	Other: Evaluations of the mechanical properties of the achilles tendon in different phases of the menstrual cycle; Monitoring assessments to verify the effect of different phases of the menstrual cycle on the neuromechanical properties of the Achilles tendon.
Physically active women using hormonal contraceptives; Physically active women using oral hormonal contraception combined with estrogen and progesterone within the last six months.	Other: Evaluations of the mechanical properties of the achilles tendon in different phases of the menstrual cycle; Monitoring assessments to verify the effect of different phases of the menstrual cycle on the neuromechanical properties of the Achilles tendon.
Sedentary women who use hormonal contraception; Sedentary women using oral hormonal contraception combined with estrogen and progesterone within the last six months.	Other: Evaluations of the mechanical properties of the achilles tendon in different phases of the menstrual cycle; Monitoring assessments to verify the effect of different phases of the menstrual cycle on the neuromechanical properties of the Achilles tendon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal voluntary isometric contraction (Nm)	Maximal voluntary isometric contraction (MVIC) of the plantar flexor muscles, i.e., largest plantar flexor torque generated in different phases of menstrual cycle and different moments of contraception use	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Achilles tendon stiffness (N/mm)	Achilles tendon stiffness will be calculated during maximal voluntary contraction in different phases of menstrual cycle and contraception users	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cross-sectional area (mm²)	The evaluation of the cross-sectional area will be carried out using ultrasound, evaluating proximal, medial and distal portions from the calcaneus bone.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
tendon stress (MPa) during maximal voluntary contractions	The stress will be obtained by taking the ratio between Achilles tendon strength and tendon cross sectional area, and tension taking the relationship between tendon elongation and tendon length at rest	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Myotendinous junction displacement (mm)	The displacement of the myotendinous junction of the medial gastrocnemius muscle (DTJM) will be evaluated during passive torque assessment.The analysis will be carried out in three core cycles of the five passive torque cycles.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Ankle functionality (cm)	Ankle functionality and ankle dorsiflexion range of motion assessed through functional heel raise theses.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Blood concentrations (pg/ml)	Blood concentrations of estrogen and progesterone in different phases of menstrual cycle	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Transvaginal ultrasound (cm)	Transvaginal ultrasound will be evaluated to control the menstrual cycle and take measurements of the ovary and uterus in the different phases of the menstrual cycle.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Tendon length (mm²)	The length of the tendon will be assessed using ultrasound, starting from the myotendinous junction to the calcaneus bone. The measurement will be carried out with a measuring tape.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Strain (%) during maximal voluntary contractions	strain will be evaluated through the relationship relationship between tendon deformation and tendon length at rest. ratio between tendon elongation and TL at rest.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Hysteresis (%)	Hysteresis measurements will be obtained from five cycles, but they will begin at 30° of plantar flexion, and the ankle will be passively moved until maximum dorsal flexion that is achieved. Both passive torque and hysteresis will be evaluated at a constant angular velocity of 5°.s	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).
Passive torque (Nm)	Passive torque will be evaluated with the isokinetic method dynamometer moving the ankle passively for five cycles, from 0° (i.e. 90° angle between foot and leg) to the maximum ROM previously determined for each participant.	The assessment will be performed at the beginning (1-4 days), middle (10-14 days), and end (22-26 days) of Cycle 1 (each menstrual cycle is between 28-30 days).

Collaborators and Investigators

• Sponsor: Marco Aurélio Vaz, PhD
• Investigators: Study Chair: Marco Vaz, Federal University of Rio Grande do Sul; Study Director: Marco Vaz, Federal University of Rio Grande do Sul; Principal Investigator: Marco Vaz, Federal University of Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2023
• Primary Completion (Estimated): January 10, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Estimated): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: estrogen; progesterone; mechanical properties; material properties; morphological properites
• Other Study ID Numbers: 5.989.983

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No