Steroid Therapy in Autoimmune Premature Ovarian Failure

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.