Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hormone Replacement in Young Women With Premature Ovarian Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00001951
Recruitment Status : Completed
First Posted : January 19, 2000
Last Update Posted : February 27, 2007
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE January 18, 2000
First Posted Date  ICMJE January 19, 2000
Last Update Posted Date February 27, 2007
Study Start Date  ICMJE December 1999
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00001951 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hormone Replacement in Young Women With Premature Ovarian Failure
Official Title  ICMJE Hormone Replacement in Young Women With Premature Ovarian Failure
Brief Summary

The human ovary produces male sex hormones (androgen) and female sex hormones (estrogen). Currently, androgen is not included in hormone replacement therapy for women with premature ovarian failure. Present hormone replacement therapy (HRT) was designed to treat women who experience ovarian failure at menopause (around the age of 50). However, 1% of women will experience premature failure of the ovaries before the age of 40. There have been no studies conducted to determine proper hormone replacement therapies for these younger women. Some research suggests that the usual menopausal hormone replacement therapy is not adequate to protect young women with premature ovarian failure from developing osteoporosis. Women with premature ovarian failure have abnormally low levels of androgens circulating in their blood. This may contribute to the increase risk for osteoporosis.

This study will compare two treatment plans for women with premature ovarian failure. Treatment plan one will be physiological estrogen hormone replacement. Treatment plan two will be physiological estrogen hormone replacement plus androgen. The study will attempt to determine which plan is more beneficial to women in relation to osteoporosis and heart disease.

The hormones will be contained in patches and given by placing the patches against the patient's skin. The patches were designed to deliver the same amount of hormone as would be normally produced by the ovary in young women.

The success of the treatment will be measured by periodically checking the density of patient's bone in the leg (femoral neck bone) . Researchers will take an initial (baseline) measurement of bone density before beginning treatment and then once a year, for 3 additional years, during treatment. The study will also consider bone density of the spine, bone turnover, heart disease risk factors, and psychological state.

Detailed Description Present menopausal hormone replacement therapy regimens were designed for women who experience ovarian failure around age 50. At least 1% of women, however, experience premature ovarian failure before the age of 40, but there have been no studies establishing optimal hormone replacement therapy regimens for these younger women. Available evidence suggests that the usual menopausal hormone replacement therapy is not adequate to protect young women with premature ovarian failure from developing osteoporosis. Women with premature ovarian failure have abnormally low circulating androgen levels, which may contribute to their risk for osteoporosis. We plan to compare physiological estrogen replacement with physiological estrogen plus androgen replacement in young women with premature ovarian failure to determine which regimen is more beneficial for bone mineral density and other metabolic parameters related to the risk for cardiovascular disease. This study employs transdermal estradiol and testosterone "patches" designed to deliver the same amount for each sex steroid normally produced by the ovary in young women in a physiological manner. Women with premature ovarian failure will be randomized to receive either estradiol plus placebo patches or estradiol plus testosterone patches. Both groups will receive cyclic progestin treatment. A group of age-matched women with normal ovarian function will serve as contemporaneous controls for bone density and other study measures. The primary outcome parameter is femoral neck bone mineral density, to be assessed at baseline, and after 1, 2, and 3 years of treatment. Other outcome parameters include lumbar spine bone mineral density, markers of bone turnover, cardiovascular disease risk factors, and cognitive function.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Healthy
  • Osteoporosis
  • Premature Ovarian Failure
Intervention  ICMJE Drug: TMTDS
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
250
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE October 2006
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE
  • 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, at least one month apart, and a normal 46, XX karotype, diagnosed with premature ovarian failure prior to the age of 40) who are between the age of 18 and 42 years will be candidates.

EXCLUSION CRITERIA:

General:

Smokers (more than 2 cigarettes per day).

Alcohol users (more than 2 drinks of alcohol per day).

Body mass index (BMI, kg/m(2)) greater than or equal to 30 and less than or equal to 19.

Previous history of hip fracture or other active hip pathology.

Abnormalities of the hip precluding the assessment of bone mineral density.

Major dermatologic disorders, or a history of skin sensitivity to adhesive bandages, tape or transdermal matrix patches.

Hirsutism score greater than 8.

Acne score greater than 1.

Hysterectomy

Baseline free testosterone (FT) levels above the normal range (greater than 6.3 pg/ml in our current essay) and/or SHBG levels less than 36 nmol/L.

Medical use:

Any prior treatment in the past 6 months known to affect bone other than estrogen (i.e., calcitonin, biphosphonates, fluoride, anabolic steroids, testosterone, or herbal therapy that contains androstenedione, and DHEA).

Current and/or past use of: diuretics, anticoagulants (heparin, Coumadin), glucocorticoid drugs, gonadotropin-releasing hormone agonist or antagonist therapy, chemotherapy.

Medical history of:

Anorexia nervosa, hyperprolactinemia, insulin-dependent diabetes, Cushing's syndrome, gastrectomy, osteogenesis imperfecta, mastocytosis, rheumatoid arthritis, long-term parenteral nutrition, hemolytic anemia, hemochromatosis and thalassemia, ankylosing spondylitis, multiple myeloma, Vitamin D deficiency, Paget's disease, primary hyperparathyroidism, hyperthyroidism, hypothyroidism, any cancer or any other major illness.

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 500 mg/dL)

LDL greater than 190mg/dl

Patients taking "statins"

Serum Alkaline phosphatase greater than or equal to 2X the upper limit of normal

Serum GGT greather than or equal to 2X the upper limit of normal

Abnormal values on two or more hepatic panel tests

Undiagnosed Vaginal Bleeding

Known sensitivity to agents

Note: We will include patients with premature ovarian failure on antidepressant medications, since today's most common antidepressant medication (Prozac) does not have a major import on cognitive function. However, we will note whether they are on these medications.

CONTROL SELECTION CRITERIA:

Healthy non-pregnant regularly menstruating women (cycles between 21 and 35 days), non-smokers, non-alcohol users, under no medications, using non-hormonal contraceptive methods (i.e. barrier methods of contraception, or sterilization) and with no intention to conceive within the following 3 years.

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 32 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001951
Other Study ID Numbers  ICMJE 000045
00-CH-0045
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date October 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP