Insulin resistance, hypersecretion of LH, and a dual-defect hypothesis for the pathogenesis of polycystic ovary syndrome.

OBJECTIVE

To review the literature dealing with the roles of insulin resistance and elevated LH levels in the development of the polycystic ovary syndrome and to outline a new hypothesis of the pathogenesis of this disorder.

DATA SOURCES

We reviewed articles on the topics of insulin resistance, elevated LH levels, and polycystic ovary syndrome that were contained in the CD-PLUS MEDLINE system data base for years 1976-1994.

METHODS OF STUDY SELECTION

Ninety-one original reports published in English-language, peer-reviewed biomedical journals were selected.

DATA EXTRACTION AND SYNTHESIS

The selected studies were reviewed critically and their conclusions were evaluated. The available literature indicates that insulin resistance and increased LH secretion are frequent features of polycystic ovary syndrome and may be important in its pathogenesis. It appears that both the amplitude and the frequency of LH pulses are increased in this disorder. Although the causes of these abnormalities of LH secretion are unknown, they could be either primary (due to increased sensitivity of LH secretion to GnRH) or secondary (due to the effects of sex steroids on LH secretion). The cause of insulin resistance in polycystic ovary syndrome also is unknown. It most likely results from a post-binding defect in the insulin action pathway. There is both in vitro and in vivo evidence that elevated LH and hyperinsulinemia act synergistically to enhance ovarian growth, androgen secretion, and ovarian cyst formation.

CONCLUSIONS

Based on the available literature, we propose a "dual-defect" hypothesis of polycystic ovary syndrome. We suggest that in a significant subset of patients, this disorder may be caused by a conjunction of two independent genetic defects: one that produces elevated LH secretion and another that produces insulin resistance. Thus, polycystic ovary syndrome develops as a result of the synergistic action of increased LH levels and hyperinsulinemia on the ovary. This working hypothesis may serve as a useful guide for further studies of the pathogenesis of polycystic ovary syndrome.