Steroid Therapy in Autoimmune Premature Ovarian Failure
Condition: Autoimmune Disease; Infertility; Premature Ovarian Failure
MeSH terms: Premature Birth; Infertility; Primary Ovarian Insufficiency; Menopause, Premature; Autoimmune Diseases
Study type: Observational

Summary: 
      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.
    

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.
    

Keywords: Infertility; Ovulation; Autoimmune; Follicle; Menopause; Biopsy; Glucocorticoids; Premature Ovarian Failure; Amenorrhea; Ovarian Failure; POF