Recently Persson et al.  performed a study to assess whether a diagnosis of polycystic ovarian syndrome (PCOS) was associated with an increased risk of type II diabetes (T2D) in later life, taking into consideration whether the PCOS was associated with hyperandrogenism (HA) or not (NA), and also taking account of body mass index (BMI) . This research question was addressed by linking six Swedish national registers. Over 52,000 women born between 1950 and 1999 with a diagnosis of PCOS or androgen excess or anovulatory infertility were included as “cases”. Over 250,000 “controls” (five per case), each born in the same month and living in the same area as their matched case, were randomly selected from the register. Whether a case had evidence of hyperandrogenism or not was determined on the basis of filled prescriptions for anti-androgenic combined oral contraceptives or other anti-androgenic drugs. The diagnosis of T2D was made on the basis of the ICD 10 code or the prescription of anti-diabetic medication, excluding metformin. The cumulative incidence rate of T2D was 1.3%, 4.4% and 14.2% for controls (non PCOS women), women with NA PCOS and those with HA PCOS, respectively. In the model which included adjustment for BMI, compared with controls, the adjusted hazard ratio for T2D in women with PCOS was 2.52 (95% CI 2.15-2.96). Compared with women with NA PCOS, the adjusted hazard ratio (HR) for women with HA PCOS was 3.86 (95% CI 3.16-4.72). In conclusion, PCOS was found to be an independent risk factor for T2D and the risk was higher for those PCOS cases with evidence of HA.
PCOS is the most common endocrine disorder identified in young women . If PCOS is associated with a greater risk of cardiovascular events in later life, then young women with PCOS could be considered a high risk group in which interventions aimed at limiting, or delaying, the development of cardiovascular disease, should be considered.
In a commentary regarding the long-term health consequences of PCOS, Fauser discussed the challenges involved in establishing such a link when there is a long delay between the diagnosis of PCOS and the development of the “hard” cardiovascular end points of death, myocardial infarction and stroke . An alternative approach is to use surrogate outcome measures such as the development of T2D. The study by Persson et al , using national Swedish registers, is an elegant example of an approach aimed at an unbiased assessment of risk of T2D in a very large sample.
However, the picture is far from clear. A recent meta-analysis that attempted to disentangle the impact of PCOS and BMI on the risk of developing T2D  reported that for non-obese women, there was no evidence of an independent effect of being diagnosed with PCOS whereas for obese women, there was evidence for an independent effect of a PCOS diagnosis. Serious methodological challenges remain. In the meta-analysis, the definitions used for both PCOS and T2D were not uniform and the number of studies included in the analyses stratified by obesity status was small . In the study of Persson et al , data on BMI was only available for parous women, although the analysis repeated using the ICD 10 code for obesity produced similar results. Of interest, in the model where BMI was available, the adjusted HR for a BMI >30 kg/m2 exceeded that for having a diagnosis of PCOS.
Finally, the use of interim indicators in young women may be hazardous if the metabolic disturbances seen in young lean women with PCOS attenuate as they age . Whether or not PCOS makes an independent contribution to cardiovascular risk, we have a responsibility to assist young obese women to reduce their future cardiovascular risk .
Robin Bell, MD
Deputy Director of the Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Persson S, Elenis E, Turkmen S, Kramer MS, Yong EL, Poromaa IS. Higher risk of type 2 diabetes in women with hyperandrogenic polycystic ovary syndrome. Fertil Steril. 2021 May 27:S0015-0282(21)00303-4. doi: 10.1016/j.fertnstert.2021.04.018.
- Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841-2855.
- Fauser BCJM. Potential later-life health implications of polycystic ovary syndrome are underserved and understudied. Fertil Steril. 2021 Jul 21:S0015-0282(21)00536-7. doi: 10.1016/j.fertnstert.2021.06.036.
- Anagnostis P, Paparodis RD, Bosdou JK, Bothou C, Macut D, Goulis DG, Livadas S. Risk of type 2 diabetes mellitus in polycystic ovary syndrome is associated with obesity: a meta-analysis of observational studies. Endocrine. 2021 Jun 26. doi: 10.1007/s12020-021-02801-2.
- Livadas S, Macut D, Bothou C, Kuliczkowska-Płaksej J, Vryonidou A, Bjekic-Macut J, Mouslech Z, Milewicz A, Panidis D. Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean women with polycystic ovary syndrome: insights from a large Caucasian cohort. Hormones (Athens). 2020;19(4):531-539.
- Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Monson RR, Speizer FE, Hennekens CH. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990;322(13):882-9.
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