Neuroendocrine control in polycystic ovary-like syndrome

Abstract

In this review article evidence is assembled from the neuroendocrinology of women with polycystic ovary-like syndrome (PCOS), to argue that the central dysregulation of gonadotropin secretion as found in the syndrome is not the cause of its development. The increased amplitude of luteinizing hormone (LH) pulses is explained by an increased pituitary sensitivity to gonadotropin releasing hormone (GnRH) due to prolonged unopposed estrogen exposure of the gonadotropic cells. The increase in pulse frequency cannot be used in the argument because it may be the cause for, as well the result of, the pathological status of the ovary. A good argument for a pathogenetic involvement of central factors, however, is the reversed day/night rhythm in adolescent girls with PCOS. A critical review of the literature does not give evidence of involvement of either obesity or catecholamines in the central abnormalities. Therefore they cannot cause PCOS via central feedback systems. The response of the gonadotropins to progesterone is the same as it is in normally cycling women. Androgens exert a variable effect on LH secretory patterns, although they do induce the typical change of PCOS in the ovaries. This argues for an ovarian rather than for a central cause. Endogenous opiates seem to be increased in PCOS. It can be argued that this should suppress both LH secretion and adrenal androgen secretion. It should also stimulate insulin-like growth factor (IGF)-binding proteins, thereby binding more IGF with less stimulatory action on the theca cells to produce androgens. Therefore endogenous opiates do not seem to be involved in the pathogenesis of PCOS either. Studies in PCOS during the recovery from GnRH agonist treatment show that the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is quite normal for some time during the recovery phase. However, PCOS always develops again. This therefore does not give a clue either. In pulsatile GnRH stimulation of PCOS patients, the LH and FSH secretory patterns completely normalize. However, the symptoms of PCOS continue under this stimulation and the clinical pattern does not change dramatically. This gives the best argument that PCOS is caused by one or more peripheral factors, which may be ovarian in origin, rather than by central factors.