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High Serum Inhibin Concentration Discriminates Autoimmune Oophoritis from Other Forms of Primary Ovarian Insufficiency

Department of Pediatrics, Obstetrics, and Reproductive Medicine (A.T., L.B., F.R., F.P.), University of Siena, 53100 Siena, Italy; and Department of Internal Medicine (S.M., A.B., P.C., M.L.B., V.B., A.F.), Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, 06126 Perugia, Italy

Address all correspondence and requests for reprints to: Alberto Falorni, M.D., Ph.D., Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, Via E.Dal Pozzo, 06126 Perugia, Italy. E-mail: falorni{at}dimisem.med.unipg.it.

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 22 women with autoimmune POI (aPOI), 71 women with 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 17-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 in women with 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 in women with 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.