Relationship Between the Menstrual Cycle and Heart Disease in Women

February 17, 2017 updated by: Jeffrey Jensen, Oregon Health and Science University

Identification of the Menstrual Cycle-Associated Factors That Modulate Circulating Lipid Levels in Premenopausal Women

Women who have regular menstrual cycles have a lower risk of heart disease than men of the same age or women who no longer have menstrual cycles. The purpose of this study is to help determine why the menstrual cycle causes a lower risk of heart disease. The investigators believe that the hormones (estradiol and progesterone) produced during the menstrual cycle, as well as the normal processes occurring in the follicle and corpus luteum (transformed follicle), change levels of "good" and "bad" cholesterol in the blood-stream. These levels of good and bad cholesterol are an important risk factor for heart disease. Therefore, our goal is to determine what effects each of these factors (estradiol, progesterone, follicle, corpus luteum) have on the levels of good and bad cholesterol in the woman's bloodstream. As many women take birth control pills, which contain synthetic forms of estradiol and progesterone that block ovulation and development of a corpus luteum, the investigators also want to determine what effect one common type of birth control pill has on levels of good and bad cholesterol.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Premenopausal women are at a lower age-adjusted risk of coronary heart disease (CHD) than men or postmenopausal women. This decreased risk of CHD is likely due, in part, to the more favorable lipid profile observed in premenopausal women. The menstrual cycle is associated with the ovarian processes of follicular growth and ovulation, and corpus luteum (CL) development, function, and regression. The steroids estrogen (E2) and progesterone (P4) are secreted from the follicle and CL, which travel via the bloodstream to elicit their effects on target tissues. The production of E2 has been implicated as the menstrual cycle-associated factor underlying the favorable lipid profile as it is known to increase atheroprotective high density lipoprotein and decrease atherogenic low density lipoprotein. However, other factors may play a role such as direct ovarian metabolism of circulating lipids. Furthermore, the role of P4 is unclear and there is some evidence that it may inhibit the beneficial effects of E2. Therefore, we aim to determine the contributions of ovarian metabolism of lipids, independent of the effects of ovarian-derived E2 and P4, to the circulating lipid profile in premenopausal women. Also, we will determine the relationship between E2 and P4, both natural and synthetic forms found in hormonal oral contraceptives, on circulating lipids. With the recent controversial findings of the Women's Health Initiative, further evaluation of the factors underlying menstrual cycle protection from CHD is warranted. This study may have implications for the management of CHD and the use of hormonal therapies in women.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Oregon Health & Sciences University, Department of Obstetrics and Gynecology, Women's Health Research Unit

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

21 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Normal menstrual cycles of 25-35 days in length for at least previous 3 cycles
  • 21-40 years of age
  • BMI > 18, < 30
  • Serum P4 > 9 ng/ml on single sample collected between days 18-25 of self-reported menstrual cycle
  • Flexible schedule allowing morning blood draws on less than 48 hour notice
  • In good general health
  • Commit to remain on stable diet during study period (no changes to normal dietary habits)
  • Commit to using non-hormonal contraceptive methods during study period except those prescribed in the experimental protocol
  • No objections to taking study drugs

Exclusion Criteria:

  • Oral contraceptive use or other hormone supplement within the preceding 2 months
  • Long-acting hormonal contraceptive use in the past 12 months (e.g., Depo-Provera®)
  • Contraindications to study drugs
  • Current or past pregnancy within the previous 6 months or currently trying to conceive
  • Desiring to conceive in the next 8 months
  • Breastfeeding in the past 2 months
  • Diagnosed Diabetes or Metabolic Syndrome
  • Current or previous use of cholesterol lowering drugs within the preceding 12 months
  • Diagnosed Polycystic Ovary Syndrome
  • History of, or self-reported, substance abuse
  • Smoker
  • Previous infertility treatment excluding male factor issues
  • Use of an investigational drug within the past 2 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

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Non-steroidal effects
Natural menstrual cycle versus Estrogen/Progesterone replacement cycle. Interventions include leuprolide acetate to induce hypogonadism and estradiol and progesterone to replace hormone levels.
Drug: leuprolide acetate
single 22.5 mg subcutaneous depot suspension
Other Names:
  • Eligard
Drug: Estradiol
0.05 to 0.3 mg transdermal daily for 26 days
Other Names:
  • Vivelle-Dot
Drug: Progesterone
50 to 100 mg vaginal suppositories twice daily for 13 days
Other Names:
  • First-Progesterone VGS
Experimental: Contraceptive effects
Oral contraceptive cycle versus Eligard treatment. Interventions include ethinyl estradiol-levonorgestrel combination and leuprolide acetate.
Drug: leuprolide acetate
single 22.5 mg subcutaneous depot suspension
Other Names:
  • Eligard
Drug: Ethinyl Estradiol-Levonorgestrel combination
0.03 mg ethinyl estradiol, 0.15 mg levonorgestrel oral daily for 21 days
Other Names:
  • Portia 21
  • Portia 28
Experimental: Steroid effects
Estrogen/Progesterone replacement cycle versus Eligard treatment. Interventions include leuprolide acetate, estradiol, and progesterone.
Drug: leuprolide acetate
single 22.5 mg subcutaneous depot suspension
Other Names:
  • Eligard
Drug: Estradiol
0.05 to 0.3 mg transdermal daily for 26 days
Other Names:
  • Vivelle-Dot
Drug: Progesterone
50 to 100 mg vaginal suppositories twice daily for 13 days
Other Names:
  • First-Progesterone VGS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Total to HDL Cholesterol Ratio
Time Frame: Entire Study
Entire Study

Collaborators and Investigators

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

Sponsor

Oregon Health and Science University

Collaborators

Medical Research Foundation, Oregon

Investigators

  • Principal Investigator: Jeffrey T Jensen, MD, MPH, Oregon Health and Science University

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

February 1, 2012

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

February 22, 2012

First Submitted That Met QC Criteria

March 1, 2012

First Posted (Estimate)

March 7, 2012

Study Record Updates

Last Update Posted (Actual)

March 22, 2017

Last Update Submitted That Met QC Criteria

February 17, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB8023

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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