Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure

June 30, 2017 updated by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Effect of Transdermal Estradiol Replacement Therapy on Ovulation Rate in Women With Premature Ovarian Failure: A Randomized, Placebo-Controlled Trial

This study will determine whether giving estrogen replacement therapy through an estradiol patch can improve ovulation rates in women with spontaneous premature ovarian failure. The ovaries are glands in women that produce female hormones and normally release an egg once a month. In women with spontaneous premature ovarian failure, the ovaries stop working too soon. Women with this disorder have abnormally high levels of leuteinizing hormone (LH) in their blood, which impedes normal ovulation. In some women, estrogen replacement can suppress LH levels to the normal range.

Women between 18 and 40 years of age with premature ovarian failure may be eligible for this 4-month study. Participants receive either standard hormone replacement therapy, consisting of an estradiol patch and progestin tablets, or placebo. The placebo group receives patches and tablets that look the same as those for the group with active treatment but they contain no hormone. All participants wear the patch every day and take the tablets the first 12 days of each month. In addition to taking the study drug, participants have blood drawn once a week for the 16 weeks of the study.

At the end of the trial, women who were in the placebo group are offered the opportunity to receive the estrogen patch and progestin therapy for another 16 weeks and continue the blood tests to determine if they ovulate on this treatment.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Premature ovarian failure (POF) is a life altering and distressing diagnosis for women due to associated infertility. Despite having amenorrhea and markedly elevated serum gonadotropin levels, approximately 50% of women with 46XX spontaneous premature ovarian failure have ovarian follicles that function intermittently. These follicles are faced with high serum LH levels. Normally, women have their LH levels in the range of 3-14 u/L except in the preovulatory stage, when it rises above 20 u/L. At that level it works on LH receptors on the granulosa cells and transforms the follicle in the corpus leutium. In POF, continuous high level of LH prematurely lutienizes growing follicles and thereby causes follicle dysfunction. We have shown by histological examination that inappropriate luteinization is a major mechanism of Graffian follicle dysfunction in these women.

We have found that approximately 50% women with premature ovarian failure have LH levels in the normal range while they are taking 100 mcg per day of our standardized transdermal estradiol therapy.

Study Type

Interventional

Phase

  • Phase 2

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
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

  • INCLUSION CRITERIA:

Patients with karyotypically normal spontaneous premature ovarian failure (as defined by screening protocol 91-CH-0127), i.e. women who have at least 4 months of amenorrhea, two FSH levels above 40 mIU/mL, or in the menopausal range, at least one month apart, and a normal 46, XX karyotype, diagnosed with premature ovarian failure prior to the age of 40 who are between the age of 18 and 40 years will be candidates.

Patients will be screened under the protocol 91-CH-0127 (Ovarian follicle function in patients with karyotypically normal spontaneous premature ovarian failure).

EXCLUSION CRITERIA:

  1. General smokers (greater than 2 cigarettes/d), alcohol users (greater than 2 drinks/d), body mass index (BMI, kg/m(2) greater than or equal to 30 and less than or equal to 19, major dermatologic disorders, or a history of skin sensitivity to adhesive bandages, tape or transdermal matrix patches
  2. Hysterectomy
  3. Medication use current and/or past use of: diuretics, anticoagulants (heparin, coumadin), glucocorticoid drugs, gonadotropin-releasing hormone agonist or antagonist therapy, chemotherapy, use of other therapies to induce ovulation such as clomiphene citrate and other assisted reproductive technologies.(At present there are no proven ways to improve ovulation rate in these women)
  4. Medical history of anorexia nervosa, hyperprolactinemia, Cushing's syndrome, gastrectomy, osteogenesis imperfecta, mastocytosis, rheumatoid arthritis, long term parenteral nutrition, hemolytic anemia, hemochromatosis and thalassemia, ankylosing spondylitis, multiple myeloma, any cancer, any other major illness
  5. Contraindications to hormone replacement therapy thromboembolic event associated with previous estrogen use history of endometrial cancer or hyperplasia history of breast cancer

hypertriglyceridemia (fasting triglyceride levels greater than 250 mg/dL) undiagnosed vaginal bleeding known sensitivity to agents.

Active liver disease with more than 3 times elevation of liver enzymes.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Serum progesterone in the ovulatory range.

Collaborators and Investigators

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

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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

August 25, 2006

Primary Completion (Actual)

December 12, 2011

Study Completion (Actual)

December 12, 2011

Study Registration Dates

First Submitted

August 29, 2006

First Submitted That Met QC Criteria

August 29, 2006

First Posted (Estimate)

August 30, 2006

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

December 12, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 060201
  • 06-CH-0201

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.

Clinical Trials on Premature Ovarian Failure

Clinical Trials on Estradiol/Medroxyprogesterone acetate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lithuania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe