J Clin Epidemiol Vol. 51, No. 7, pp. 581–586, 1998 0895-4356/98/$19.00 Copyright  1998 Elsevier Science Inc. All rights reserved. PII S0895-4356(98)00035-3 Mortality of Women with Polycystic Ovary Syndrome at Long-term Follow-up T. Pierpoint, 1 P. M. McKeigue, 1, * A. J. Isaacs, 1,3 S. H. Wild, 1 and H. S. Jacobs 2 1 Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine; 2 Division of Endocrinology, University College London Medical School; and 3 Department of Academic Therapeutics, Chelsea and Westminster Hospital, London ABSTRACT. Metabolic disturbances associated with insulin resistance are present in most women with polycys- tic ovary syndrome. This has led to suggestions that women with polycystic ovary syndrome may be at increased risk of cardiovascular disease in later life. We undertook a long-term follow-up study to test whether cardiovascu- lar mortality is increased in these women. A total of 786 women diagnosed with polycystic ovary syndrome in the United Kingdom between 1930 and 1979 were traced from hospital records and followed for an average of 30 years. Standardized mortality ratios (SMRs) were calculated to compare the death rates of these women with national rates. The SMR for all causes was 0.90 (95% CI, 0.69–1.17), based on 59 deaths. There were 15 deaths from circulatory disease, yielding an SMR of 0.83 (95% CI, 0.46–1.37). Of these 15 deaths, 13 were from ischemic heart disease (SMR 1.40; 95% CI, 0.75–2.40) and two were from other circulatory disease (SMR 0.23; 95% CI, 0.03–0.85). There were six deaths from diabetes mellitus as underlying or contributory cause, compared with 1.7 expected (odds ratio 3.6; 95% CI, 1.5–8.4). Breast cancer was the commonest cause of death (SMR 1.48 based on 13 deaths; 95% CI, 0.79–2.54). We conclude that women with polycystic ovary syndrome do not have markedly higher than average mortality from circulatory disease, even though the condition is strongly associated with diabetes, lipid abnormalities, and other cardiovascular risk factors. The characteristic endocrine profile of women with polycystic ovary syndrome may protect against circulatory disease in this condition. j clin epidemiol 51;7:581–586, 1998.  1998 Elsevier Science Inc. KEY WORDS. Polycystic ovary syndrome, mortality, insulin, resistance, cardiovascular disease INTRODUCTION The objectives of this study were to determine whether PCOS in young women is associated with increased cardio- Polycystic ovary syndrome (PCOS) is now recognized to be vascular mortality in later life, and more generally to estab- very common; about 20% of women of reproductive age lish whether the condition has long-term consequences for have polycystic ovaries on ultrasound, and about half of women’s health. these have clinical or biochemical evidence of anovulation and androgen excess [1–3]. In comparison with controls, women with PCOS are resistant to insulin-mediated glu- METHODS cose uptake [4] and have other metabolic disturbances asso- Sample Size ciated with insulin resistance: glucose intolerance [5], hy- From published studies of cardiovascular risk factors [8,9] in perinsulinemia [5], high plasma triglyceride [6], low plasma women with PCOS, and cohort studies in which these risk high-density-lipoprotein (HDL) cholesterol [7,8], and cen- factors had been measured in women at baseline [17,18], we tral obesity [9]. This pattern corresponds to the insulin resis- estimated that a three-fold relative risk of coronary heart tance syndrome described in other groups at high risk of disease in women with PCOS compared with the general non-insulin-dependent diabetes and coronary heart disease population was plausible. For 90% power to detect a three- [10,11]. We [8,12] and others [6,13–15] have therefore sug- fold relative risk at 5% significance, the expected number gested that women with PCOS may be at increased risk of of events must be at least five. At current mortality rates coronary heart disease in later life, especially if the distur- for England and Wales, five deaths from CHD would be bances of lipid and carbohydrate metabolism persist after expected if 1400 women were followed to age 55 years, or the menopause as a study in Sweden has indicated [16]. 600 women were followed to age 60 years. As the age distri- * Address for correspondence: Dr. Paul McKeigue, Department of Epidemi- bution of the cohort could not be accurately estimated in ology and Population Health, London School of Hygiene and Tropical advance, a target of at least five expected deaths from CHD Medicine, Keppel Street, London WC1E 7HT, UK. Accepted for publication on 23 March 1998. was set for the sample size.