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Relationship Between the Menstrual Cycle and Heart Disease in Women

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ClinicalTrials.gov Identifier: NCT01546454
Recruitment Status : Completed
First Posted : March 7, 2012
Results First Posted : October 23, 2014
Last Update Posted : March 22, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment
Coronary Heart Disease Drug: Ethinyl Estradiol-Levonorgestrel combination Drug: leuprolide acetate Drug: Estradiol Drug: Progesterone

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Identification of the Menstrual Cycle-Associated Factors That Modulate Circulating Lipid Levels in Premenopausal Women
Study Start Date : February 2012
Primary Completion Date : June 2012
Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Estradiol
U.S. FDA Resources

Arms and Interventions

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 Name: Eligard
Drug: Estradiol
0.05 to 0.3 mg transdermal daily for 26 days
Other Name: Vivelle-Dot
Drug: Progesterone
50 to 100 mg vaginal suppositories twice daily for 13 days
Other Name: First-Progesterone VGS
Experimental: Contraceptive effects
Oral contraceptive cycle versus Eligard treatment. Interventions include ethinyl estradiol-levonorgestrel combination and leuprolide acetate.
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
Drug: leuprolide acetate
single 22.5 mg subcutaneous depot suspension
Other Name: Eligard
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 Name: Eligard
Drug: Estradiol
0.05 to 0.3 mg transdermal daily for 26 days
Other Name: Vivelle-Dot
Drug: Progesterone
50 to 100 mg vaginal suppositories twice daily for 13 days
Other Name: First-Progesterone VGS

Outcome Measures

Primary Outcome Measures :
  1. Total to HDL Cholesterol Ratio [ Time Frame: Entire Study ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01546454

United States, Oregon
Oregon Health & Sciences University, Department of Obstetrics and Gynecology, Women's Health Research Unit
Portland, Oregon, United States, 97239-3098
Sponsors and Collaborators
Oregon Health and Science University
Medical Research Foundation, Oregon
Principal Investigator: Jeffrey T Jensen, MD, MPH Oregon Health and Science University
More Information

Responsible Party: Jeffrey Jensen, Director, Women's Health Research Unit, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01546454     History of Changes
Other Study ID Numbers: IRB8023
First Posted: March 7, 2012    Key Record Dates
Results First Posted: October 23, 2014
Last Update Posted: March 22, 2017
Last Verified: February 2017

Keywords provided by Jeffrey Jensen, Oregon Health and Science University:
Premenopausal women
coronary heart disease
menstrual cycle

Additional relevant MeSH terms:
Heart Diseases
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Vascular Diseases
Arterial Occlusive Diseases
Polyestradiol phosphate
Ethinyl Estradiol
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Ethinyl estradiol, levonorgestrel drug combination
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Fertility Agents, Female
Fertility Agents