The Effect of Menstrual Cycle on the Results of Treadmill Exercise Test With High Sensitive Cardiac Troponin Levels After Exercise in Women

False positive results are commonly observed in women after exercise treadmill test (ETT). The effects of menstrual periodic changes on the results of exercise treadmill test in premenopausal women have not been clearly defined. Primary purpose of the study is to investigate the biological causes of false positive test results in the treadmill exercise test in premenopausal women. Estrogen is known to have direct vasodilatory effects on coronary arteries. Early and late follicular phases of the menstrual cycle are characterized by low and high estrogen levels, respectively. The Early Follicular Phase starts on the first day of the menstrual cycle and ends when oestradiol begins to increase. It is characterised by increasing LH and FSH and constant low levels of oestradiol. The late follicular phase starts with the increase in oestradiol and ends at its preovulatory peak. The hypothesis of the study is that ETT results will change at the early and late follicular phases in premenstrual women. Premenopausal women between the ages of 18-40, who apply to the cardiology outpatient clinics of Göztepe City Hospital with typical/atypical chest pain, and an indication for ETT will be included in the study. ETT will be performed in the early and late follicular phases of the menstrual cycle, separately.

Study Overview

• Status: Recruiting
• Conditions: Menstrual Cycle Disorder; Exercise Induced Ischemia
• Intervention / Treatment: Diagnostic test: Exercise Treadmill Test (ETT)

Detailed Description

Estrogen is known to have direct vasodilatory effects on coronary arteries. Early and late follicular phases of the menstrual cycle in premenopausal women are characterized by low and high estrogen levels, respectively. The Early Follicular Phase starts on the first day of the menstrual cycle and ends when oestradiol begins to increase. It is characterised by increasing LH and FSH and constant low levels of oestradiol. The late follicular phase starts with the increase in oestradiol and ends at its preovulatory peak. Premenopausal women (between the ages of 18-40), who apply to the cardiology outpatient clinics of Göztepe City Hospital with typical/atypical chest pain, and an indication for exercise treadmill test (ETT) will be included in the study. ETT will be performed in the early and late follicular phases of the menstrual cycle, separately.

Forty (40) patients who meet these conditions will be included in the study.

The menstrual cycle of the patient will be questioned in the screening interview. Premenopausal female patients between the ages of 18-40 who still have a regular menstrual cycles will be included in the study. Hormone levels including Estradiol III, follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (Elecsys) will be measured to confirm the menstrual cycle before each ETT. ETT will be performed in the early and late follicular phases of the menstrual cycle, separately. Cardiac high sensitive troponin I (hs cTnI) (Roche) will be measured before and after ETT.

Primary end point will the ST/HR (heart rate) index (μV/bpm) in ETT. The ST/HR index (μV/bpm) is automatically generated by the General Electronic GE Healthcare T2100-ST Treadmill & CASE 6.73 Stress Test System.

The secondary endpoints will be the change in hs cTnI between the before and after ETT, maximal exercise capacity (METs score), ST/HR slope (μV/bpm), maximal horizontal or down slope ST segment depression (mm) with exercise. Secondary end points other than cTnI are automatically generated by the General Electronic GE Healthcare T2100-ST Treadmill & CASE 6.73 Stress Test System.

The null hypothesis is that there is no difference between in the ST/HR index (μV/bpm) between the menstrual phases. The power is calculated to prove the alternative hypothesis in which there is a 50 % difference between the ETT ST/HR index (μV/bpm). In a paired study sample, with type I error of 5 % and type II error of 20 %, the sample size is calculated as 34 patients.

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

Contacts and Locations

• Study Contact: Name: Mehmet Agirbasli, MD; Phone Number: 90(532)7468840; Email: agirbasli@gmail.com
• Study Contact Backup: Name: Mehmet Agirbasli; Email: agirbasli@gmail.com

Study Locations

• Turkey
  • Istanbul, Turkey, 34722
    • Recruiting
    • Istanbul Medeniyet University Hospital, Goztepe
    • Contact: Mehmet Agirbasli; Phone Number: 90(532)7468840; Email: agirbasli@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients in the premenopausal period between the ages of 18-60, who apply to the cardiology outpatient clinics of Göztepe City Hospital with typical/atypical chest pain, and an exercise treadmill test results positive according to the routine positivity criteria of the exercise test will be included in the study.

Description

Inclusion Criteria:

1. Patients with suspected ischemia in the exercise test
2. Age is ≥18
3. Female patients in the pre-menopausal period
4. Patients who can understand and sign the consent form

Exclusion Criteria:

1. Patients with history of coronary artery disease or myocardial infarction
2. Secondary Hypertension, Uncontrolled hypertension
3. Peripheral artery disease
4. Patients with severe heart valve disease
5. Cardiac arrhythmia
6. Heart failure
7. Cancer patients
8. Severe kidney (stage ≥ 3 kidney failure) chronic liver disease
9. Those who do not have the level of consciousness or mental capacity to understand and accept to participate in the study
10. Pregnancy
11. Those who use external hormonal therapy or drugs that will change the hormone level i.e. oral contraceptives
12. Acute pericarditis, myocarditis or myopericarditis
13. Sepsis, systemic infections
14. Women with signs and symptoms of perimenopause or menopause.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exercise test results will be grouped based on the menstrual cycle.; Positive exercise treadmill tests will be repeated at a different phase of menstrual cycle in premenopausal women (early versus late follicular phase).	Diagnostic test: Exercise Treadmill Test (ETT); Routinely ordered exercise treadmill test results will be reviewed in premenopausal women. ETT results and change in hs cTnI levels will be compared between the early and late follicular phases of menstrual cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ST/HR index (μV/bpm) in ETT.	The ST/HR index (μV/bpm) is automatically generated by the General Electronic GE Healthcare T2100-ST Treadmill & CASE 6.73 Stress Test System.	March-September 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the concentrations of high sensitive cardiac troponin I (ng/L) change before and after exercise	hs cTnI will be measured by Roche kit.	May-September 2023
maximal exercise capacity (METs score)	automatically generated by the General Electronic GE Healthcare T2100-ST Treadmill & CASE 6.73 Stress Test System.	May-September 2023
ST/HR slope (μV/bpm)	automatically generated by the General Electronic GE Healthcare T2100-ST Treadmill & CASE 6.73 Stress Test System.	May-September 2023
maximal horizontal or down slope ST segment depression (mm) with exercise	automatically generated by the General Electronic GE Healthcare T2100-ST Treadmill & CASE 6.73 Stress Test System.	May-September 2023

Collaborators and Investigators

• Sponsor: Istanbul Medeniyet University
• Investigators: Study Director: Sukru Sadık Öner, MD PhD, Istanbul Medeniyet University City Hospital Goztepe

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): September 1, 2023
• Study Completion (Estimated): October 1, 2023

Study Registration Dates

• First Submitted: July 18, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Menstruation Disturbances; Ischemia
• Other Study ID Numbers: 2023/0129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The results will be published as journal article

Drug and device information, study documents

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