Feasibility Study for Development of an Early Test for 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. Identifier: NCT00006156
Recruitment Status : Completed
First Posted : August 10, 2000
Results First Posted : May 16, 2013
Last Update Posted : May 16, 2013
National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
Lawrence Nelson, M.D., National Institutes of Health Clinical Center (CC)

Brief Summary:

This purpose of this study is to gain information about normal ovarian function that will be useful in developing a test for early detection of ovarian failure. The ovaries produce female hormones, such as estrogen, that are important in maintaining a woman's health. When the ovaries do not work properly, problems can develop. Unfortunately, there is no test that can detect ovarian failure early in its course. By the time premature ovarian failure is diagnosed in young women, two-thirds have already developed osteopenia (loss of some bone mass) and nearly one in ten have osteoporosis, a greater loss of bone mineral density that weakens bones and increases the risk of fractures.

Women with normal ovarian function ages 18 to 55 and postmenopausal women 60 years of age or older may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests and vaginal ultrasound examination. For the ultrasound study, a probe that emits sound waves is inserted into the vagina, and the sound waves are converted to form images of the ovaries. The procedure is done with an empty bladder and takes about 10 minutes. After this screening visit (Visit 1), those enrolled in the study will return to the NIH Clinical Center for the following additional procedures:

Visit 2-Will be scheduled between days 3 and 5 of the menstrual cycle (for women who are still menstruating). Participants will have blood tests to measure hormone levels and to check for pregnancy, and will have another transvaginal ultrasound examination. They will then receive an injection of a synthetic form of follicle stimulating hormone (FSH), a hormone the body makes normally.

Visits 3 and 4-Will be scheduled 24 and 36 hours after the FSH injection given during Visit 2 for collection of blood samples.

Visit 5-Will be scheduled 48 hours after the FSH injection for additional blood sampling and a final transvaginal ultrasound examination.

Condition or disease Intervention/treatment Phase
Healthy Premature Ovarian Failure Other: Control Drug: Drug: FSH Not Applicable

Detailed Description:
This is a pilot project to test the feasibility of developing an FSH stimulation test. There is a need for a sensitive and specific marker to detect ovarian insufficiency early in its course. FSH stimulates inhibin B production by the granulosa cells of the cohort of ovarian follicles; serum inhibin B in turn participates in the negative feedback loop regulating FSH secretion. This protocol is characterizing the normal FSH-stimulated serum inhibin B response to a single subcutaneous injection of 300 IU human recombinant FSH given on day 2 to 4 of the menstrual cycle. In preliminary analysis under this protocol we have demonstrated that FSH-stimulated serum inhibin B levels measured at 24 hours after injection is a more robust marker of functional ovarian age than ovarian follicle count by transvaginal ultrasound, basal serum Mullerian Inhibiting Substance (MIS) levels, or basal serum FSH levels. Multiple regression analysis has revealed that FSH-stimulated inhibin B, FSH-stimulated estradiol, and basal FSH contribute significantly to an ability to predict functional ovarian age (as approximated by chronological age). The resulting regression equation relating these three parameters with age has a correlation coefficient of 0.742 and a coefficient of determination of 0.551. The protocol is now evaluating the reproducibility of this test and the feasibility of generating normative data in young women between the ages of 18 and 25. The results of this study may define parameters that could lead to earlier diagnosis and treatment of premature ovarian insufficiency.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: FSH-Stimulated Inhibin B as a Marker for Early Ovarian Insufficiency
Study Start Date : August 2000
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: Control
Control for FSH stimulation test
Other: Control
No injection of FSH

Experimental: Drug: FSH
FSH Stimulation Test
Drug: Drug: FSH
FSH Stimulation Test

Primary Outcome Measures :
  1. Follicle Stimulating Hormone Stimulated Serum Inhibin B Levels. [ Time Frame: 24 hours ]

Secondary Outcome Measures :
  1. Follicle Stimulating Hormone Stimulated Serum Estradiol (E2) Levels [ Time Frame: 24 hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

A. Women with normal ovarian function:

Age 18 to 55.

Normal body mass index (18-30 kg/m(2)).

Normal menstrual cycles (between 25-35 days in length).

Ovulatory serum progesterone concentrations (in excess of 6 ng/mL in the menstrual cycle just preceding the study cycle).

B. Postmenopausal women (to serve as negative controls):

Greater than or equal to 60 years of age.

Proven fertility (as evidenced by a history of pregnancy regardless of outcome).

Normal body mass index (18-30 kg/m(2)).

Naturally menopausal: amenorrhea for at least one year; serum FSH greater than 40 IU/mL.

C. Women carriers of FMR1 premutations:

Age 18 to 40.

50 to 200 CGG repeats.

Normal menstrual cycles (between 25-35 days in length).

Have previously had genetic counseling regarding their FMR1 status.


History of infertility or infertility in a first degree relative.

Acute or chronic disease.

Menopause due to surgery, radiation, or chemotherapy.

Current use of oral contraceptives or hormone replacement therapy, or use of these agents within the previous 3 months.

Use within the previous three months of any medication known to affect the hypothalamic-pituitary-ovarian axis (including over-the-counter and alternative medicines).

History of excessive exercise (greater than 10 hours a week).

Girls will be excluded because there are no data regarding FSH use in children.



Breast feeding.

Persistent ovarian masses.

History of tumors of the ovary, breast, uterus, hypothalamus, or pituitary.

History of breast or endometrial cancer.

History of hypersensitivity to recombinant FSH or any one of its excipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006156

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health Clinical Center (CC)

Responsible Party: Lawrence Nelson, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC) Identifier: NCT00006156     History of Changes
Other Study ID Numbers: 000189
First Posted: August 10, 2000    Key Record Dates
Results First Posted: May 16, 2013
Last Update Posted: May 16, 2013
Last Verified: March 2013

Keywords provided by Lawrence Nelson, M.D., National Institutes of Health Clinical Center (CC):
Ovarian Failure
Healthy Volunteer
Primary Ovarian Insufficiency(POI)
Premature Menopause
Premature Ovarian Failure (POF)

Additional relevant MeSH terms:
Primary Ovarian Insufficiency
Premature Birth
Menopause, Premature
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases