A Pharmacokinetic Evaluation of Bioidentical Compounded Estrogen Cream and Natural Progesterone

NCT00864214 | Completed Phase 1 DMC

• 2 other identifiers: 06-00636308-000223
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Menopause

Keywords

bioidentical hormone; menopause; estrogen; progesterone

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Day 1 and Day 15

Secondary Outcomes (3)

• 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.

  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.

  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.

  Day 1

Study Arms (4)

1

EXPERIMENTAL

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)

2

EXPERIMENTAL

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)

3

EXPERIMENTAL

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)

4

EXPERIMENTAL

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)

Interventions

bioidentical hormone (Biest) DRUG

Estrogen is the Biest 2.0 mg bioidentical cream; the placebo is the transdermal patch; the progesterone is compounded progesterone-100 mg

1

bioidentical hormone (Vivelle-Dot) DRUG

Estrogen is the Vivelle-Dot patch 0.05 mg; the placebo is the transdermal cream; the progesterone is micronized progesterone-100 mg

4

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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;
• Medical conditions increasing the risk of complications from hormone replacement such as uncontrolled hypertension (\>160/100 mmHg), smoking, diabetes and lupus;
• Current use of estrogen, progesterone or testosterone;Depending on the drug, it could be 7 days to 6 months.
• Current use of isoflavone containing products;
• Current use of protein binding medications like rifampin, warfarin, antiepileptic drugs (effect on estrogen bioavailability);
• 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
• Women with alcohol or substance abuse or dementia (compliance issues).
• Women who are more than ten years from their last menstrual period (unfavorable risk : benefit ratio)
• Women with peanut allergy (Prometrium has peanut oil)
• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Sood R, Warndahl RA, Schroeder DR, Singh RJ, Rhodes DJ, Wahner-Roedler D, Bahn RS, Shuster LT. Bioidentical compounded hormones: a pharmacokinetic evaluation in a randomized clinical trial. Maturitas. 2013 Apr;74(4):375-82. doi: 10.1016/j.maturitas.2013.01.010. Epub 2013 Feb 4.

  PMID: 23384975 DERIVED

MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Richa Sood, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 17, 2009
• First Posted: March 18, 2009
• Study Start: June 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: April 1, 2010
• Last Updated: January 16, 2012

Record last verified: 2012-01

Locations

US (1)