Relationship Between the Menstrual Cycle and Heart Disease in Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Oregon Health and Science University
Sponsor:
Collaborator:
Medical Research Foundation, Oregon
Information provided by (Responsible Party):
Jeffrey Jensen, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT01546454
First received: February 22, 2012
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

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 Intervention
Coronary Heart Disease
Drug: Ethinyl Estradiol-Levonorgestrel combination
Drug: leuprolide acetate
Drug: Estradiol
Drug: Progesterone

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Identification of the Menstrual Cycle-Associated Factors That Modulate Circulating Lipid Levels in Premenopausal Women

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Change from baseline in total cholesterol to high density lipoprotein cholesterol ratio following ovarian suppression and steroid replacement [ Time Frame: Baseline month and one month of ovarian suppression with steroid replacement ] [ Designated as safety issue: No ]
  • Change from baseline in total cholesterol to high density lipoprotein cholesterol ratio after estradiol and progesterone replacement [ Time Frame: 3 week baseline and 4 weeks of estradiol and progesterone replacement ] [ Designated as safety issue: No ]
  • Change from baseline in total cholesterol to high density lipoprotein cholesterol ratio after monophasic hormonal oral contraceptive use [ Time Frame: Baseline month and 3 weeks of oral contraceptive use ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in serum low density lipoprotein cholesterol following ovarian suppression and steroid replacement [ Time Frame: Baseline month and one month of ovarian suppression with steroid replacement ] [ Designated as safety issue: No ]
  • Change from baseline in serum low density lipoprotein cholesterol after estradiol and progesterone replacement [ Time Frame: 3 week baseline and 4 weeks of estradiol and progesterone replacement ] [ Designated as safety issue: No ]
  • Change from baseline in serum low density lipoprotein cholesterol after monophasic combined hormonal oral contraceptive use [ Time Frame: One month baseline and 3 weeks of oral contraceptive use ] [ Designated as safety issue: No ]
  • Change from baseline in serum high density lipoprotein cholesterol following ovarian suppression and steroid replacement [ Time Frame: Baseline month and one month of ovarian suppression with steroid replacement ] [ Designated as safety issue: No ]
  • Change from baseline in serum high density lipoprotein cholesterol after estradiol and progesterone replacement [ Time Frame: 3 week baseline and 4 weeks of estradiol and progesterone replacement ] [ Designated as safety issue: No ]
  • Change from baseline in serum high density lipoprotein cholesterol after monophasic combined hormonal oral contraceptive use [ Time Frame: One month baseline and 3 weeks of oral contraceptive use ] [ Designated as safety issue: No ]
  • Change from baseline in serum triglycerides following ovarian suppression and steroid replacement [ Time Frame: Baseline month and one month of ovarian suppression with steroid replacement ] [ Designated as safety issue: No ]
  • Change from baseline in serum triglycerides after estradiol and progesterone replacement [ Time Frame: 3 week baseline and 4 weeks of estradiol and progesterone replacement ] [ Designated as safety issue: No ]
  • Change from baseline in serum triglycerides after monophasic combined hormonal oral contraceptive use [ Time Frame: One month baseline and 3 weeks of oral contraceptive use ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: February 2012
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Ethinyl Estradiol-Levonorgestrel combination
    0.03 mg ethinyl estradiol, 0.15 mg levonorgestrel daily for 21 days
    Other Names:
    • Portia 21
    • Portia 28
    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
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.

  Eligibility

Ages Eligible for Study:   21 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546454

Contacts
Contact: Jeffrey T Jensen, MD, MPH 503-494-0111 jensenje@ohsu.edu
Contact: Randy L Bogan, PhD 503-614-3751 boganr@ohsu.edu

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

No publications provided

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
Study First Received: February 22, 2012
Last Updated: October 9, 2012
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on August 21, 2014