Feasibility Study for Development of an Early Test for Ovarian Failure
Condition: Healthy; Premature Ovarian Failure
MeSH terms: Premature Birth; Primary Ovarian Insufficiency; Menopause, Premature
Study type: Interventional

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.
    

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.
    

Intervention name(s): Control; Drug: FSH
Intervention type(s): Other; Drug
Intervention description(s): No injection of FSH; FSH Stimulation Test
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Ovarian Failure; Ovary; Aging; Healthy Volunteer; Primary Ovarian Insufficiency(POI); Premature Menopause; Premature Ovarian Failure (POF)