Effect of Estradiol+Drospirenone Versus Estradiol+MPA on Endothelial Function

Effect of Combined Estradiol and Drospirenone Treatment Versus Combined Estradiol and Medroxyprogesterone Acetate Treatment on Endothelial Function: A Crossover Study

This study compares the effects of two common hormone medications on the heart and blood vessels of healthy post-menopausal women over the age of 45.

The study will take place over the course of about 5 months. Each subject will take two different medications over two six-week periods. They will be randomized at the beginning of the study to either estradiol+medroxyprogesterone acetate or estradiol+drospirenone for the first period, and will receive the other medication the second six-weeks of the study. At the very beginning of the study and at the end of each six-week treatment period, subjects will come to the hospital various tests including non-invasive blood vessel imaging tests, blood draws to test the levels of certain hormones in the body, an oral glucose tolerance test, a test to monitor renal blood flow, and 24-hour blood pressure monitoring. Between treatment periods, there will be a four-week medication-free washout period.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Drug: Estradiol+MPA; Drug: Estradiol+Drospirenone

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy female postmenopausal volunteers, as defined by absence of menses for at least 12 months and follicle stimulating hormone (FSH) 30 IU/L;
2. Age 45 to 75 years;
3. Systolic blood pressure <140 and >90 mmHg and diastolic blood pressure <90 and >60 mmHg at the screening visit;
4. No personal history of diabetes;
5. Body mass index < 30 kg/m2;
6. No clinically significant abnormalities on screening tests (complete blood count, serum electrolytes, liver enzymes, thyroid stimulating hormone, urinalysis, and electrocardiogram).

Exclusion Criteria:

1. Current smoking, defined as smoking within the 12 months before the screening visit;
2. Alcohol intake >1 beverage per night or history of alcohol abuse;
3. Current or past recreational drug use;
4. Personal history of hypertension, cardiovascular disease (coronary artery disease, congestive heart failure, valvular heart disease, stroke, transient ischemic attack, or intermittent claudication), hyperlipidemia, diabetes (defined as a fasting glucose ≥126 mg/dL), kidney disease, liver disease, venous or arterial thromboembolic disease, adrenal insufficiency, depression, or illness requiring overnight hospitalization in the past 6 months;
5. Risk factors for arterial or venous thromboembolism;
6. Personal history of breast cancer or any other type of cancer;
7. Personal history of endometrial hyperplasia, endometrial cancer, or unexplained vaginal bleeding;
8. History of cervical cancer or abnormal pap smear
9. Prescription or herbal medication use, excluding thyroid hormone supplementation;
10. Ischemic changes on resting electrocardiogram;
11. Serum creatinine ≥ 1.3 mg/dL.
12. Serum potassium level > 5.0 mmol/L;
13. Known hypersensitivity to any of the study drugs;
14. Other active medical problems detected by examination or laboratory testing, except for treated hypothyroidism.
15. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Estradiol+MPA	Drug: Estradiol+MPA; 1 single pill dose daily containing estradiol 1 mg + medroxyprogesterone acetate 2.5 mg; Other Names: Estradiol+medroxyprogesterone acetate
Active Comparator: Estradiol+DRSP	Drug: Estradiol+Drospirenone; 1 single pill dose daily containing estradiol 1mg + drospirenone 0.5 mg; Other Names: Angeliq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD)	This crossover study examined the effects of E+MPA versus E+DRSP on brachial artery reactivity (BAR) assessed after six weeks of treatment. BAR is a noninvasive measure of endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. With this technique, inflation of an arm blood pressure cuff to suprasystolic blood pressure causes relative ischemia downstream to the cuff. Upon deflation, a brief state of increased blood flow occurs (reactive hyperemia), and the resulting increase in shear stress causes nitric oxide release and resulting vasodilation of the brachial artery (flow-mediated vasodilation). The flow-mediated changes in brachial artery diameter can be imaged by ultrasound and measured as an index of peripheral vasomotor function. BAR correlates with invasive assessments of coronary endothelial function as well as multiple cardiovascular risk factors.	%FMD after 6 weeks of treatment

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Bayer
• Investigators: Principal Investigator: Ellen Seely, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 22, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 23, 2010

Study Record Updates

• Last Update Posted (Estimate): July 12, 2016
• Last Update Submitted That Met QC Criteria: June 10, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Cardiovascular, vascular
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Natriuretic Agents; Diuretics; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Contraceptive Agents, Male; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Medroxyprogesterone Acetate; Medroxyprogesterone; Drospirenone; Drospirenone and ethinyl estradiol combination
• Other Study ID Numbers: 2006p002137

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No