Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Premature Ovarian Failure
Intervention: Estradiol/Medroxyprogesterone acetate (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: National Institute of Child Health and Human Development (NICHD) Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
Summary
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.
Clinical Details
Official title: Effect of Transdermal Estradiol Replacement Therapy on Ovulation Rate in Women With Premature Ovarian Failure: A Randomized, Placebo-Controlled Trial
Study design: 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 40 Years.
Gender(s): Female.
Criteria:
- 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.
Locations and Contacts
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting
Additional Information
NIH Clinical Center Detailed Web Page
Related publications: Wright CS, Jacobs HS. Spontaneous pregnancy in a patient with hypergonadotrophic ovarian failure. Br J Obstet Gynaecol. 1979 May;86(5):389-92.
Starting date: August 2006
Last updated: May 23, 2008
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