Steroid Therapy in Autoimmune Premature Ovarian Failure

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001306
First received: November 3, 1999
Last updated: December 13, 2011
Last verified: December 2011
  Purpose

No therapy for infertile patients with premature ovarian failure has been proven effective. Some anecdotal reports have suggested that high dose, long term prednisone (steroid) therapy may be useful in treating autoimmune ovarian failure. However, prednisone, when used in high-doses for long periods of time has substantial side effects, including aseptic necrosis of bone where portions of bone die without the presence of infection and are surrounded by healthy tissue. Aseptic necrosis of bone often requires major surgical treatment. Even with this known level of risk, patients with premature ovarian failure are being treated based on this anecdotal evidence.

This study will test the hypothesis that a lower risk therapy (alternate-day, lower dose, shorter-term prednisone) will cause a remission of autoimmune ovarian failure. There is no reliable blood test to identify patients who have premature ovarian failure. Therefore, all patients must undergo a laparoscopic ovarian biopsy to confirm the presence of an auto immune reaction in the ovaries (autoimmune oophoritis). Laparoscopy is a surgical procedure that allows doctors to explore the abdomen using a camera-like device called a laparoscope. The procedure has been used clinically by some reproductive endocrinologists to identify patients with premature ovarian failure who have an autoimmune mechanism for the disorder.

The treatment will be deemed successful based on the return of ovulation as determined by weekly serum progesterone levels.


Condition
Autoimmune Disease
Infertility
Premature Ovarian Failure

Study Type: Observational
Official Title: Autoimmune Premature Ovarian Failure: A Controlled Trial of Alternate-Day Prednisone Therapy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 33
Study Start Date: July 1992
Estimated Study Completion Date: December 2011
Detailed Description:

Autoimmune oophoritis is a distinct clinical entity and a known cause of premature ovarian failure. It is characterized by the presence of circulating adrenal antibodies. No therapy for infertile patients with premature ovarian failure due to autoimmune oophoritis has been proven effective by prospective controlled study. Anecdotal reports have suggested that high-dose, long-term prednisone therapy may be useful in treating autoimmune ovarian failure. However, prednisone, when used in high-dose for a long-term has substantial side effects, including aseptic necrosis of bone requiring major surgical intervention. Despite this risk, patients with premature ovarian failure are being treated based on this anecdotal evidence. We are aware of two patients with premature ovarian failure who developed aseptic necrosis of bone on high-dose, long-term prednisone therapy administered elsewhere.

This protocol will test the hypothesis that a lower risk therapy (alternate-day, lower dose, shorter-term prednisone) will induce remission of ovarian failure caused by autoimmune oophoritis. The protocol will use a double-masked, placebo-controlled design. Patients with premature ovarian failure who have serologic evidence of steroidogenic cell autoimmunity will be candidates. Successful outcome will be defined as a return of ovulation as determined by weekly serum progesterone levels. The hypothesis that short-term, alternate-day prednisone therapy restores ovulation will be tested with an equality of proportions test comparing the proportion of patients who ovulate during placebo with the proportion of patients who ovulate during prednisone therapy.

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION/EXCLUSION CRITERIA:

Women 18 to 39 years of age with premature ovarian failure who meet the following requirements will be candidates for the study:

At least a four month history of amenorrhea not due to pregnancy,

Clearly elevated gonadotropins with a serum FSH greater than or equal to 40 IU/L on two separate occasions at least one month apart,

Positive adrenal or ovarian antibodies demonstrated by indirect immuno-fluorescence using monkey tissue as substrate or other laboratory evidence of steroidogenic cell autoimmunity such as the presence of antibodies against 21-hydroxylase,

No evidence for genetic, metabolic, toxic, or iatrogenic cause of the ovarian failure,

No medical contraindication to glycocorticoid therapy,

No glycocorticoid therapy taken in the past year (patients on appropriate replacement therapy for Addison's disease are not excluded),

No medical contraindication to pregnancy.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001306

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001306     History of Changes
Other Study ID Numbers: 920223, 92-CH-0223
Study First Received: November 3, 1999
Last Updated: December 13, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Infertility
Ovulation
Autoimmune
Follicle
Menopause
Biopsy
Glucocorticoids
Premature Ovarian Failure
Amenorrhea
Ovarian Failure
POF

Additional relevant MeSH terms:
Primary Ovarian Insufficiency
Autoimmune Diseases
Infertility
Menopause, Premature
Adnexal Diseases
Endocrine System Diseases
Genital Diseases, Female
Genital Diseases, Male
Gonadal Disorders
Immune System Diseases
Ovarian Diseases

ClinicalTrials.gov processed this record on October 21, 2014