High serum inhibin concentration discriminates autoimmune oophoritis from other forms of primary ovarian insufficiency

Context: Primary ovarian insufficiency (POI) is defined by hypergonadotropic amenorrhea occurring before the age of 40 yr. In 4-5% of women with POI, an ovarian autoimmune process can be demonstrated. Design: We have determined the serum concentrations of total inhibin and inhibin B by sensitive ELISAs in 22womenwith autoimmune POI (aPOI), 71womenwith non-autoimmune idiopathic POI (iPOI), 77 postmenopausal women, and 90 healthy, fertile women (HW). Diagnosis of aPOI was made according to the presence of steroid cell autoantibodies and/or 17α-hydroxylase autoantibodies and/or cytochrome P450 side-chain cleavage autoantibodies. All aPOI patients were also positive for adrenal autoantibodies. Results: Total inhibin levels were significantly higher inwomenwith aPOI (median, 281 pg/ml) than in women with iPOI (median, 74 pg/ml) or HW (median, 133.5 pg/ml) (P < 0.001). Levels of inhibin B were also significantly higher in women with aPOI (median, 109 pg/ml) than in women with iPOI (median, 18 pg/ml) (P < 0.001) or HW (median, 39 pg/ml) (P < 0.05). Serum concentrations of total inhibin and inhibin B were significantly higher inwomenwith POI than in postmenopausal women (P < 0.001), irrespective of the presence/absence of autoantibodies. At receiver-operating characteristic analysis, cutoff values of 133 pg/ml for total inhibin and 60.5 pg/ml for inhibin B ensured 86.4% sensitivity and 81-84.5% specificity for aPOI vs. iPOI. Conclusions: We conclude that a variable degree of ovarian function is preserved in women with POI and that aPOI is characterized by increased inhibin production resulting from a selective theca cell destruction, with initial preservation of granulosa cells.