Neuroendocrinology of the polycystic ovary syndrome

Abstract

The clinical and biochemical heterogeneity of the PCOS is mirrored by the range of neuroendocrine disturbances described in women with PCOS. An increased serum LH concentration is a common, although not ubiquitous, feature and occurs primarily as a result of an increase in the amplitude of pulsatile LH, and presumably GnRH, secretion. The frequency of pulsatile GnRH secretion may, however, be increased in certain patients and may conceivably increase LH bioactivity by altering glycosylation of the molecule. Vigorous debate continues as to whether the observed changes in gonadotrophins are a primary abnormality or occur secondary to alterations in peripheral steroid concentrations. The proponents of the frequency hypothesis point to the discordant changes in gonadotrophin secretion that may be induced by rapid frequency exogenous GnRH stimulation in patients with hypogonadotrophic hypogonadism. Those who believe that the inappropriate gonadotrophin secretion is a secondary phenomenon argue that manipulation of peripheral steroid levels, by either administration of oestrogen/progesterone, induced ovulation or ovarian diathermy, may correct the disturbance of gonadotrophin secretion, which is therefore presumably a consequence of changes in ovarian steroid feedback signals. The weight of evidence at present suggests that the inappropriate gonadotrophin secretion is usually a secondary abnormality, although there may be groups of patients with a primary increase in GnRH pulsatility. The search for a unifying neuroendocrine disturbance in PCOS has been frustrated by the inability to find consistent evidence of disordered central dopaminergic, opioidergic, noradrenergic or serotoninergic pathways. Those abnormalities which have been uncovered appear to be secondary to chronic anovulation rather than of primary pathological import, and emphasize the central importance of the ovary as culprit rather than victim in PCOS.