Genetics of polycystic ovary syndrome – on the way to diabetes?

S Franks

Institute of Reproductive & Developmental Biology, Imperial College London
Hammersmith Hospital, London W12 0NN

Summer School 13-16 July 2004
St Anne's College, Oxford University, UK

Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy to affect women of reproductive age. It is the major cause of both anovulatory infertility and of hirsutism but it is also associated with a characteristic metabolic abnormality, central to which is insulin resistance and hyperinsulinaemia. Women with PCOS are at increased risk of developing type2 diabetes (T2D) in later life. This review explores the possibility of common aetiological factors, the impact of metabolic disturbance on reproductive function and long-term health, and approaches to management of the metabolic consequences of PCOS.

We have used a candidate gene approach to identify susceptibility loci for PCOS, particularly in genes affecting the secretion and action of insulin. In parallel we have performed physiological studies of the effects of insulin/insulin resistance on ovarian and cardiovascular function. The effects of dietary intervention and of insulin sensitising agents on reproductive and metabolic function have been explored.

PCOS has a major genetic basis. Polymorphism of the variable-number tandem repeat (VNTR) in the regulatory region of the insulin gene may confer susceptibility to PCOS but nutritional factors also have a significant impact on reproductive and metabolic phenotype. Lifestyle changes and insulin-sensitising agents, such as metformin, improve reproductive function and are likely to reduce the risk of developing T2D and cardiovascular disease.

PCOS and T2D appear to share common aetiological factors; they are both complex traits characterised by important interactions between genetic and environmental (nutritional) factors. Lifestyle changes should be the main interventional aim in at-risk subjects, to reduce the incidence of T2D and cardiovascular events.

References

Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R, McCarthy M. The genetic basis of polycystic ovary syndrome (review). Hum Reprod 1997, 12 2641-2648

Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism of action and implications for pathogenesis. Endocr Rev 1997, 18 774-800

Abbott DH, Dumesic DA, Franks S. Developmental origin of polycystic ovary syndrome – a hypothesis. J Endocrinol 2002, 174 1-5

Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003, 3 CD003053

The opinions expressed in this paper are those of the speaker and do not necessarily reflect the views of the Society

Revised: 05-Nov-2004