Relationship Between the Menstrual Cycle and Heart Disease in Women

NCT ID: NCT01546454

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2013-01-31

Brief Summary

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.

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.

Conditions

Coronary Heart Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

leuprolide acetate

Intervention Type: DRUG

single 22.5 mg subcutaneous depot suspension

Estradiol

Intervention Type: DRUG

0.05 to 0.3 mg transdermal daily for 26 days

Progesterone

Intervention Type: DRUG

50 to 100 mg vaginal suppositories twice daily for 13 days

Contraceptive effects

Oral contraceptive cycle versus Eligard treatment. Interventions include ethinyl estradiol-levonorgestrel combination and leuprolide acetate.

Group Type: EXPERIMENTAL

Ethinyl Estradiol-Levonorgestrel combination

Intervention Type: DRUG

0.03 mg ethinyl estradiol, 0.15 mg levonorgestrel oral daily for 21 days

leuprolide acetate

Intervention Type: DRUG

single 22.5 mg subcutaneous depot suspension

Steroid effects

Estrogen/Progesterone replacement cycle versus Eligard treatment. Interventions include leuprolide acetate, estradiol, and progesterone.

Group Type: EXPERIMENTAL

leuprolide acetate

Intervention Type: DRUG

single 22.5 mg subcutaneous depot suspension

Estradiol

Intervention Type: DRUG

0.05 to 0.3 mg transdermal daily for 26 days

Progesterone

Intervention Type: DRUG

50 to 100 mg vaginal suppositories twice daily for 13 days

Interventions

Ethinyl Estradiol-Levonorgestrel combination

0.03 mg ethinyl estradiol, 0.15 mg levonorgestrel oral daily for 21 days

Intervention Type: DRUG

leuprolide acetate

single 22.5 mg subcutaneous depot suspension

Intervention Type: DRUG

Estradiol

0.05 to 0.3 mg transdermal daily for 26 days

Intervention Type: DRUG

Progesterone

50 to 100 mg vaginal suppositories twice daily for 13 days

Intervention Type: DRUG

Other Intervention Names

Portia 21; Portia 28; Eligard; Vivelle-Dot; First-Progesterone VGS

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical Research Foundation, Oregon

OTHER

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Jensen

Director, Women's Health Research Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey T Jensen, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Oregon Health & Sciences University, Department of Obstetrics and Gynecology, Women's Health Research Unit

Portland, Oregon, United States

Countries

United States

Other Identifiers

IRB8023

Identifier Type: -

Identifier Source: org_study_id