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

• ClinicalTrials.gov Identifier: NCT01109979
• Recruitment Status: Completed
• First Posted: April 23, 2010
• Results First Posted: May 3, 2013
• Last Update Posted: July 12, 2016
• Sponsor: Brigham and Women's Hospital
• Collaborator: Bayer
• Information provided by (Responsible Party): Ellen W. Seely, Brigham and Women's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases	Drug: Estradiol+MPA; Drug: Estradiol+Drospirenone	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Effect of Combined Estradiol and Drospirenone Treatment Versus Combined Estradiol and Medroxyprogesterone Acetate Treatment on Endothelial Function: A Crossover Study
• Study Start Date: December 2009
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: June 2016

Arms and Interventions

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 Name: Estradiol+medroxyprogesterone acetate
Active Comparator: Estradiol+DRSP	Drug: Estradiol+Drospirenone; 1 single pill dose daily containing estradiol 1mg + drospirenone 0.5 mg; Other Name: Angeliq

Outcome Measures

Primary Outcome Measures :

1. Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD) [ Time Frame: %FMD after 6 weeks of treatment ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

Bayer

Investigators

• Principal Investigator: Ellen Seely, MD; Brigham and Women's Hospital

More Information

• Responsible Party: Ellen W. Seely, M.D., Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01109979
• Other Study ID Numbers: 2006p002137
• First Posted: April 23, 2010
• Results First Posted: May 3, 2013
• Last Update Posted: July 12, 2016
• Last Verified: June 2016

Keywords provided by Ellen W. Seely, Brigham and Women's Hospital:

Cardiovascular, vascular

Additional relevant MeSH terms:

Cardiovascular Diseases; Medroxyprogesterone Acetate; Drospirenone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Medroxyprogesterone; Drospirenone and ethinyl estradiol combination; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contraceptives, Oral; Contraceptives, Oral, Synthetic; Contraceptive Agents, Male; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents