Relationship Between the Menstrual Cycle and Heart Disease in Women

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

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	Not Applicable

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
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: January 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 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

• Ages Eligible for Study: 21 Years to 40 Years (Adult)
• Sexes 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

Locations

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

Investigators

• 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
• Other Study ID Numbers: IRB8023
• First Posted: March 7, 2012
• 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; lipids

Additional relevant MeSH terms:

Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Leuprolide; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Estradiol; Polyestradiol phosphate; Progesterone; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Fertility Agents, Female; Fertility Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents