Evaluating the Association Between Endometrial Cancer and Polycystic Ovary Syndrome

Zeina Haoula; Maisa Salman; William Atiomo

Disclosures

Hum Reprod. 2012;27(5):1327-1331. 

In This Article

Discussion

This is the first systematic review and meta-analysis to have demonstrated an unambiguous link between PCOS and EC. The data used in the previously published meta-analysis (Chittenden et al., 2009) revealed that the 95% CIs of the ORs of three of the four studies used in the meta-analysis crossed 1 (no evidence of an effect) and the effect size of the published aggregated OR (2.70) of increased EC risk in women with PCOS was because of one case–control study of 399 women with newly diagnosed EC compared with 3040 controls (Escobedo et al., 1991) in which the OR for EC was 4.2 (95% CI: 1.7–10.4) in women with infertility associated with 'ovarian' factors. In our paper, this meta-analysis has been boosted by data from a large Australian study (Fearnley et al., 2010) and it showed that women with PCOS were found to have a 3-fold risk of developing EC compared with controls with 95% CIs clearly >1. This translates into a 9% lifetime risk of EC in Caucasian women with PCOS compared with 3% in women without it. The study also confirmed that although PCOS was first suggested as a risk factor for EC >60 years ago (Speert, 1949), in a study where an increased incidence of cystic ovaries in young women with EC was noted, the exact strength of this association has never been clear (Hardiman et al., 2003;Chittenden et al., 2009).

Several uncontrolled or retrospective cohort studies to the first study suggesting a link between PCOS and EC (Speert, 1949) either did not demonstrate a link (Jackson and Dockerty, 1957; Ramzy and Nisker, 1979; Ho et al., 1997), or reported data which was not suitable for inclusion in a meta-analysis (Dockerty et al., 1951; Coulam et al., 1983; Gallup and Stock, 1984; Dahlgren et al., 1991; Wild et al., 2000). For example, Dockerty et al. (1951) in their case series of young women with endometrial carcinoma noted a high incidence of associated fibromyoma, myohypertrophy and endometrial hyperplasia, which were thought to indicate 'chronic hyperestrogenism' but the study was uncontrolled. In another example, Jackson and Dockerty (1957) described 43 patients with Stein–Leventhal syndrome (PCOS) and 16 of these women were identified by examining surgical specimens removed from a group of 'several thousand patients' with EC. The remaining 27 patients were women with symptoms of the Stein–Leventhal syndrome and a confirmatory ovarian biopsy. Endometrial tissue was available for examination in only 15 of these cases. Thirteen samples showed 'thickening', 2 were atrophic, but there were no reported cases of endometrial carcinoma. Nevertheless, Jackson and Dockerty concluded that their most important observation concerned the link between the Stein–Leventhal syndrome (PCOS) and endometrial carcinoma.

The main limitation of this study was the diagnosis of PCOS among the participants of the studies chosen for the meta-analysis, one of them (Escobedo et al., 1991) was published before the first NIH consensus on PCOS definition; in the other two studies (Niwa et al., 2000; Iatrakis et al., 2006) PCOS participants were enrolled based on a diagnosis by a physician, without other specifications. In the study of Pillay et al. (2006), PCOS women were characterized by the presence of PCOs on ovarian sections and Fearnley et al. (2010) characterized their PCOS participants based on self-reported diagnosis. These could have led to selection biases amongst PCOS women.

A large proportion of the studies identified in the literature search also either had small patient groups or did not have control groups, which limited the number of studies eligible for meta-analysis. The published OR EC risk in PCOS in one study (Fearnley et al., 2010) was 4.0 (95% CI: 1.7–9.3; unadjusted for BMI) which was different from the OR we calculated [3.76 (95% CI: 1.76–7.52)] for their study and used in our meta-analysis based on the primary data presented in the paper. We attempted to make contact with the authors to clarify this minor discrepancy in the data with no success. We however did not think the magnitude of difference was significant. In addition, of two of the studies used in the meta-analysis showed OR with 95% CI of <0.5 to >170.0 (Fig. 3), meaning that no significant risk could be determined.

In conclusion, this study showed that women with PCOS had an OR of developing EC of 2.89 with a 95% CI of 1.52–5.48. This almost 3-fold risk of EC in women with PCOS translates into a lifetime risk of 9% given the background lifetime risk of EC in the general population of 3%. Although most women with PCOS (91%) will not develop EC, our study has shown that they are more likely at increased risk. This finding strengthens evidence base in support of link between PCOS and EC. It has relevant implications for clinical practice as it calls for the implementation of risk-reducing measures including the potential of introducing a screening programme for early cancer detection as treatment of EC at an early stage is associated with an excellent 86% 5-year survival rate. What seems indispensable for proper evaluation of this issue is the need for further studies to clarify the question of the association between EC and PCOS such as large follow-up prospective population studies with clearly defined cases, controls and study outcomes/end-points that will enable clinicians to draw firmer conclusions and improve the care of women with PCOS.

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