Relationship Between the Menstrual Cycle and Heart Disease in Women

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01546454
• Collaborator: Medical Research Foundation, Oregon (Other)
• Enrollment: 5
• Location: 1
• Arms: 3
• Duration (Months): 11
• Patients Per Site Per Month: 0.5

Study Details

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	Phase
Coronary Heart Disease	Drug: Ethinyl Estradiol-Levonorgestrel combination; Drug: leuprolide acetate; Drug: Estradiol; Drug: Progesterone	N/A

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
• 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: Feb 1, 2012
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jan 1, 2013

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 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: 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 Names: 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 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

Outcome Measures

Primary Outcome Measures

1. Total to HDL Cholesterol Ratio [Entire Study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 40 Years
• 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

Locations

	Site	City	State	Country	Postal Code
1	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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey Jensen, Director, Women's Health Research Unit, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01546454
• Other Study ID Numbers: IRB8023
• First Posted: Mar 7, 2012
• Last Update Posted: Mar 22, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Jeffrey Jensen, Director, Women's Health Research Unit, Oregon Health and Science University: Premenopausal women; coronary heart disease; menstrual cycle; lipids
• Additional relevant MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Leuprolide; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Estradiol; Polyestradiol phosphate; Progesterone

Study Results

Participant Flow

Pre-assignment Detail	One enrolled participant was lost to follow-up prior to receiving any interventions.

Arm/Group Title	All Study Participants
Arm/Group Description
Period Title: Natural Menstrual Cycle
STARTED	4
COMPLETED	4
NOT COMPLETED	0
Period Title: Natural Menstrual Cycle
STARTED	4
COMPLETED	4
NOT COMPLETED	0
Period Title: Natural Menstrual Cycle
STARTED	4
COMPLETED	4
NOT COMPLETED	0
Period Title: Natural Menstrual Cycle
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Total to HDL Cholesterol Ratio
Time Frame	Entire Study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-steroidal Effects	Contraceptive Effects	Steroid Effects
Arm/Group Description	Natural menstrual cycle versus Estrogen/Progesterone replacement cycle. Interventions include leuprolide acetate to induce hypogonadism and estradiol and progesterone to replace hormone levels. leuprolide acetate: single 22.5 mg subcutaneous depot suspension Estradiol: 0.05 to 0.3 mg transdermal daily for 26 days Progesterone: 50 to 100 mg vaginal suppositories twice daily for 13 days	Oral contraceptive cycle versus Eligard treatment. Interventions include ethinyl estradiol-levonorgestrel combination and leuprolide acetate. Ethinyl Estradiol-Levonorgestrel combination: 0.03 mg ethinyl estradiol, 0.15 mg levonorgestrel oral daily for 21 days leuprolide acetate: single 22.5 mg subcutaneous depot suspension	Estrogen/Progesterone replacement cycle versus Eligard treatment. Interventions include leuprolide acetate, estradiol, and progesterone. leuprolide acetate: single 22.5 mg subcutaneous depot suspension Estradiol: 0.05 to 0.3 mg transdermal daily for 26 days Progesterone: 50 to 100 mg vaginal suppositories twice daily for 13 days
Measure Participants	4	4	4
Mean (95% Confidence Interval) [Total to HDL Cholesterol Ratio]	0.146	0.148	-0.89

Adverse Events

Arm/Group Title	All Study Participants
Arm/Group Description
All Cause Mortality
	All Study Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.