Refractoriness to gonadotropin therapy: how to distinguish ovarian failure versus pseudoovarian resistance caused by neutralizing antibodies.

Ovarian resistance to exogenously administered gonadotropins and elevated serum gonadotropins, especially follicle-stimulating hormone (FSH), are considered virtually diagnostic of ovarian failure. However, similar clinical findings can be caused by circulating antibodies to gonadotropins which can neutralize the biologic activity of exogenously administered gonadotropins and can also cause falsely high gonadotropin determinations by routine double-antibody radioimmunoassay (RIA). We have used a primate model with anti-FSH antibodies to demonstrate that an acute course of combined estrogen-progestin therapy will suppress the pituitary secretion of FSH, which is markedly elevated in ovarian failure, while the false FSH elevations caused by circulating anti-FSH antibodies are not reduced by steroid negative feedback. Thus, gonadotropin (RIA) determinations before versus during an acute course of estrogen and progesterone therapy can distinguish true ovarian failure from the presence of circulating anti-gonadotropin antibodies.