A Pharmacokinetic Evaluation of Bioidentical Compounded Estrogen Cream and Natural Progesterone (HRT)

January 12, 2012 updated by: Mayo Clinic
Bioidentical compounded hormone therapy (BCHT) is considered a 'safer' option to the conventional hormones (HT) by its proponents. However, there is limited research data to support their claims. Our group at the Women's Health Clinic, in collaboration with the Departments of Endocrinology, Complementary Medicine and Laboratory Medicine, is interested in developing a line of research to test the safety and efficacy of BCHT. In the present study, we aim to find the dose of BCHT that is bioequivalent to conventional HT, in a randomized, blinded, four-arm, phase I clinical trial. We will estimate the levels of estrone (E1), estradiol (E2) and estriol (E3) at baseline and at steady state with two-weeks of administration of three commonly used doses of bioidentical compounded estrogen cream (Biest) and a standard dose conventional estrogen patch (Vivelle-Dot). E1, E2, and E3 values will be summarized using point estimates and 95% confidence intervals. Two-sample t-test will be used to compare each Biest group to the Vivelle-Dot group. Healthy postmenopausal women, with no contraindications for hormone use, who are able to fully understand and participate in the trial, will be enrolled. We will utilize the resources of Mayo CRU to conduct this study.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is designed as a Phase I, blinded, randomized, four-arm clinical trial. Participants will be randomized to one of the four interventions: Biest transdermal cream 2.0 mg/0.5 g daily, Biest 2.5 mg/0.5 g daily, Biest 3.0 mg/0.5 g daily or Vivelle-Dot patch 0.05 mg/24 hours changed biweekly. Serum levels of E1, E2, E3 and progesterone will be obtained at baseline before starting the intervention and then multiple times on days 1 15 and 16 of study, as outlined in the table below (Table 3.1). The peak and steady state concentrations of E1, E2 and E3, along with time to reach the peak levels, and area under the curve will be calculated. Baseline and steady state levels of progesterone will also be compared between the compounded and micronized progesterone groups. If there are abnormalities in estrogen levels or symptoms suggesting such, a vaginal ultrasound would be done to exclude possible ovarian activity as a source.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Women 40-60 years old;
  2. Postmenopausal status, as documented by absence of periods for ≥ 1 year or amenorrhea for ≥ 6 months along with FSH ≥ 40 IU/L;
  3. Surgical menopause;
  4. History of a normal mammogram within the last 11 months;
  5. Normal screening labs (within 20% of upper limit of lab normal);
  6. Able to understand and sign informed consent; and
  7. Able and willing to be in a monitored CRU setting and provide blood samples as requested.

Exclusion Criteria:

  1. Contraindications to the use of hormones because of personal history of coronary artery disease, stroke, breast cancer, DVT/PE, active liver or gall bladder disease, hormone dependent migraine headaches, endometrial, ovarian or other hormone dependent cancers;
  2. Medical conditions increasing the risk of complications from hormone replacement such as uncontrolled hypertension (>160/100 mmHg), smoking, diabetes and lupus;
  3. Current use of estrogen, progesterone or testosterone;Depending on the drug, it could be 7 days to 6 months.
  4. Current use of isoflavone containing products;
  5. Current use of protein binding medications like rifampin, warfarin, antiepileptic drugs (effect on estrogen bioavailability);
  6. Family history of premenopausal breast cancer in a first degree relative, two or more premenopausal breast cancers in second degree relatives, male breast cancer, ovarian cancer in two or more relatives and; and
  7. Women with alcohol or substance abuse or dementia (compliance issues).
  8. Women who are more than ten years from their last menstrual period (unfavorable risk : benefit ratio)
  9. Women with peanut allergy (Prometrium has peanut oil)
  10. Women who are found to have premenopausal estrogen levels, as confirmed by a baseline Estradiol level of >35 pg/ml and vaginal ultrasound suggesting ovarian activity.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
Estrogen is the Biest 2.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 2.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 2.5 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 3.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Experimental: 2
Estrogen is the Biest 2.5 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 2.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 2.5 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 3.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Experimental: 3
Estrogen is the Biest 3.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 2.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 2.5 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Drug: bioidentical hormone (Biest)
Estrogen is the Biest 3.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg
Experimental: 4
Estrogen is the Vivelle-Dot patch 0.05 mg; the placebo is the transdermal cream; the progesterone is micronized progesterone-100 mg
Drug: bioidentical hormone (Vivelle-Dot)
Estrogen is the Vivelle-Dot patch 0.05 mg; the placebo is the transdermal cream; the progesterone is micronized progesterone-100 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To measure estrone, estradiol and estriol levels at baseline and after achieving a steady state with 15-days of administration of three commonly used doses of bioidentical compounded estrogen cream and a standard dose conventional estrogen patch.
Time Frame: Day 1 and Day 15
Day 1 and Day 15
To measure the progesterone levels at baseline and after achieving a steady state with 15-days of administration of 100 mg/day of two different oral progesterone formulations.
Time Frame: Day 1 and Day 15
Day 1 and Day 15

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To assess the feasibility of conducting a clinical trial randomizing patients to daily estradiol-estriol transdermal cream or biweekly estradiol patch for 15 days in 40 healthy postmenopausal women.
Time Frame: Day 1 and Day 15
Day 1 and Day 15
To assess the tolerability of use of daily estradiol-estriol transdermal cream and biweekly estradiol patch for 15 days in 40 healthy postmenopausal women in a randomized clinical trial.
Time Frame: Day 1 and Day 15
Day 1 and Day 15
To test if genetic variation in SULT1A1 copy number and single nucleotide polymorphisms (SNPs) influences estrogen pharmacokinetics in 40 healthy postmenopausal women receiving exogenous estrogen therapy.
Time Frame: Day 1
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Richa Sood, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 16, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 06-006363
  • 08-000223

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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