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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
Sponsor:
Collaborator:
Medical Research Foundation, Oregon
Information provided by (Responsible Party):
Jeffrey Jensen, Oregon Health and Science University

Tracking Information
First Submitted Date  ICMJE February 22, 2012
First Posted Date  ICMJE March 7, 2012
Results First Submitted Date  ICMJE April 11, 2014
Results First Posted Date  ICMJE October 23, 2014
Last Update Posted Date March 22, 2017
Study Start Date  ICMJE February 2012
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2014)
Total to HDL Cholesterol Ratio [ Time Frame: Entire Study ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2012)
  • 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 ]
  • 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 ]
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2012)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Change from baseline in serum triglycerides after estradiol and progesterone replacement [ Time Frame: 3 week baseline and 4 weeks of estradiol and progesterone replacement ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Relationship Between the Menstrual Cycle and Heart Disease in Women
Official Title  ICMJE Identification of the Menstrual Cycle-Associated Factors That Modulate Circulating Lipid Levels in Premenopausal Women
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Coronary Heart Disease
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: leuprolide acetate
    • Drug: Estradiol
    • Drug: Progesterone
  • Experimental: Contraceptive effects
    Oral contraceptive cycle versus Eligard treatment. Interventions include ethinyl estradiol-levonorgestrel combination and leuprolide acetate.
    Interventions:
    • Drug: Ethinyl Estradiol-Levonorgestrel combination
    • Drug: leuprolide acetate
  • Experimental: Steroid effects
    Estrogen/Progesterone replacement cycle versus Eligard treatment. Interventions include leuprolide acetate, estradiol, and progesterone.
    Interventions:
    • Drug: leuprolide acetate
    • Drug: Estradiol
    • Drug: Progesterone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 17, 2014)
5
Original Estimated Enrollment  ICMJE
 (submitted: March 1, 2012)
15
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 21 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01546454
Other Study ID Numbers  ICMJE IRB8023
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jeffrey Jensen, Oregon Health and Science University
Study Sponsor  ICMJE Oregon Health and Science University
Collaborators  ICMJE Medical Research Foundation, Oregon
Investigators  ICMJE
Principal Investigator: Jeffrey T Jensen, MD, MPH Oregon Health and Science University
PRS Account Oregon Health and Science University
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP