The Effects of Hormonal Contraceptives on Incidence of ACL Injury Within Menstrual Cycle Phases

May 8, 2023 updated by: Tom Wycherley, University of South Australia

The aim of this study is to investigate how hormonal contraceptives affect ACL rupture incidence within menstrual cycle phases. It is thought hormones such as estrogen and progesterone (which fluctuate throughout the normal menstrual cycle) play a role in the laxity of ligaments within the body. It is hypothesised that around the time of ovulation the ACL undergoes increased laxity, leaving it more likely to be injured. This study will look at the phase of the menstrual cycle in which the ACL injuries occur and whether there are differences due to the use and type of hormonal contraception participants may be using (such as Combined oral contraceptive, Mirena, Implanon), which can modify the levels of circulating estrogen and progesterone.

This study involves participants completing an anonymous electronic survey after presenting to a sports or orthopaedic clinic with an ACL rupture. The survey collects information about participant's current ACL injury and any previous knee injuries; typical menstrual cycle patterns and the use of hormonal contraception; and history of sports participation. Responses will be analysed to look for similarities and differences in ACL injury occurrence by menstrual cycle phase and hormonal contraceptive use.

The study hypotheses are:

  1. Hormonal contraceptives that are known to reduce ovulatory rises in estrogen will have the most consistent pattern of ACL rupture incidence across all phases of the menstrual cycle.
  2. There will be a mitigated risk of ACL rupture in the preovulatory phase of the menstrual cycle, relative to the other phases, in women using hormonal contraception compared to those not using hormonal contraception
  3. There will be a higher proportion of ACL ruptures during the preovulatory phase of the menstrual cycle in non-hormonal contraceptive users.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Anterior Cruciate ligament (ACL) rupture has been observed at higher rates in females than males during sporting competition, particularly during the preovulatory phase of the menstrual cycle. During the menstrual cycle, estrogen secretion varies from 10 to 100 fold throughout the cycle. A possible explanation for the ACL injuries being observed in the preovulatory phase, is that increases in estrogen levels increases the laxity of the ACL, predisposing it to risk of rupture. Studies investigating knee joint laxity, concluded that increased joint laxity was associated with an increased risk of ACL injury. In addition, measurement of knee laxity found no changes in laxity over time in males, but greater anterior displacement of the knee during the preovulatory phase of the menstrual cycle compared with the ovulatory and postovulatory phases in women.

Use of hormonal contraception typically maintains estradiol levels at ~25 pg/ml and decreases the ovulatory rise in estrogen. A study of the use of hormonal contraceptive in alpine skiers with ACL rupture reported that 74% of women were in the preovulatory phase (vs 26% in the postovulatory), experienced an ACL rupture. However, in women with ACL rupture in the preovulatory phase, 72.5% of the women were not using a hormonal contraceptive. A recent systematic review suggested an association between hormonal fluctuations and ACL injury and that hormonal contraceptives offer 20% reduction in risk of injury. Multiple modalities of hormonal and contraceptive control are available to females within Australia, but the efficacy of different hormonal contraceptives for reducing the risk of ACL rupture is unknown.

This study aims to investigate: 1) whether there are differences in risk of an ACL rupture incidence within menstrual cycle phases in females using different types of hormonal contraception. 2) whether there are differences in the pattern of ACL rupture incidence within menstrual cycle phases in females using vs not using hormonal contraception. 3) whether ACL rupture incidence in female athletes not using hormonal contraceptives are more prevalent during the pre-ovulatory phase of the menstrual cycle.

The study will use a cross-sectional design, with data being collected in women presenting at sports medicine or orthopaedic clinics with ACL rupture. On presentation at the clinic with ACL rupture, the study will be introduced to patients by a clinician and they will be shown a recruitment flyer that includes a QR code. On scanning the QR code patients will be taken to a RedCap survey website that they can enter an email in to receive, via automated reply email, a Participant Information Sheet and link to an anonymous study survey. The survey will take approximately 7 minutes to complete and asks questions about how the participants ACL injury occurred, any previous knee injuries, their menstrual cycle phase that the injury occurred in, their usual menstrual cycle characteristics, their use of hormonal contraceptives and the main sport they play.

Injury data will be analyzed according to menstrual cycle phase to confirm whether the preovulatory phase presents higher risk of ACL rupture than the ovulatory/postovulatory phase. Data will be stratified by hormonal contraception use and type to evaluate whether the injury occurrence pattern within the menstrual cycle differs by hormonal contraceptive use, such that the anticipated higher incidence in the preovulatory phase is mitigated with hormonal contraceptive use (and type).

The study hypotheses are:

  1. Hormonal contraceptives that are known to reduce ovulatory rises in estrogen will have the most consistent pattern of ACL rupture incidence across all phases of the menstrual cycle.
  2. There will be a mitigated risk of ACL rupture in the preovulatory phase of the menstrual cycle, relative to the other phases, in women using hormonal contraception compared to those not using hormonal contraception
  3. There will be a higher proportion of ACL ruptures during the preovulatory phase of the menstrual cycle in non-hormonal contraceptive users.

Study Type

Observational

Enrollment (Anticipated)

240

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • UniSA Allied Health and Human Performance
        • Contact:
        • Contact:
        • Principal Investigator:
          • Rob Buckley, MD
        • Sub-Investigator:
          • Mikaeli Carmichael, B.Ap.Sci

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Females who present to a sports or orthopaedic clinic with an ACL rupture that occurred within the previous 3 months

Description

Inclusion Criteria:

  • Presenting to a sports or orthopaedic clinic with an acute ACL rupture of their knee that occurred within the last 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
ACL Rupture
Female, aged 18-40 years of age with an acute ACL rupture of the knee that occurred within the last 3 months, who presented to a sports or orthopaedic clinic
Other: ACL Rupture
Female, aged 18-40 years of age with an acute ACL rupture of the knee that occurred within the last 3 months, who presented to a sports or orthopaedic clinic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ACL Injury Menstrual Cycle Phase by Hormonal Contraceptive Type
Time Frame: Baseline
In which phase of the menstrual cycle did the ACL injury occur, by hormonal contraceptive type (including non-use reference)
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ACL Injury Menstrual Cycle Phase by Hormonal Contraceptive Use
Time Frame: Baseline
In which phase of the menstrual cycle did the ACL injury occur, by hormonal contraceptive use vs. non-use
Baseline
ACL Injury Menstrual Cycle Phase Overall
Time Frame: Baseline
In which phase of the menstrual cycle did the ACL injury occur (pooled group)
Baseline

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
ACL Injury Menstrual Cycle Phase, sensitivity analysis (Contact vs Non-Contact)
Time Frame: Baseline
Examine robustness considering contact vs non contact injuries.
Baseline
ACL Injury Menstrual Cycle Phase, sensitivity analysis (Previous knee injury)
Time Frame: Baseline
Examine robustness considering previous serious knee injury (yes vs. no)
Baseline
ACL Injury Menstrual Cycle Phase, sensitivity analysis (playing history/level)
Time Frame: Baseline
Examine robustness considering player competition level
Baseline
ACL Injury Menstrual Cycle Phase, sensitivity analysis (menstrual cycle status)
Time Frame: Baseline
Examine robustness considering menstrual cycle status
Baseline
ACL Injury Menstrual Cycle Phase, sensitivity analysis (menstrual cycle recall confidence)
Time Frame: Baseline
Examine robustness considering menstrual cycle recall confidence
Baseline
ACL Injury Menstrual Cycle Phase, sensitivity analysis (age)
Time Frame: Baseline
Examine robustness considering age
Baseline
ACL Injury Menstrual Cycle Phase, sensitivity analysis (BMI)
Time Frame: Baseline
Examine robustness considering body mass index
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of South Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

July 6, 2021

First Submitted That Met QC Criteria

July 22, 2021

First Posted (Actual)

August 2, 2021

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

May 8, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Buckley_2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data to be made available on request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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