Hyperandrogenemic-hypothalamic ovarian insufficiency – a new disease entity

Abstract

Six women initially diagnosed as suffering from primary or secondary hypothalamic amenorrhea were treated for ovulation induction for up to 140 days with pulsatile administration of GnRH. All women had low circulating LH and FSH levels, normal prolactin concentrations and testosterone serum levels in the low normal range. None of the patients was suffering from insulin resistance as determined by glucose tolerance test. There was no indication for the presence of polycystic ovaries. Initially, all patients did respond to pulsatile GnRH administration with ovulation and corpus luteum formation. However, during continuation of treatment, there was a continuing increase of LH and the LH/FSH ratio as well as a progressive rise in serum testoterone levels resulting in hyperandrogenemia. This was accompagnied by the development of polycystic ovaries and cessation of follicular maturation. We conclude from these observations that restoration of normal GnRH stimulation of the pituitary gland can result in the development of hyperandrogenemia and polycystic ovaries, suggesting a pituitary or primary ovarian defect underlying the pathogenesis of this disorder.