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

Abstract and Introduction

Abstract

BACKGROUND Given the current lack of clarity in the published literature, we performed a systematic review of the literature to determine the exact strength of the association between polycystic ovary syndrome (PCOS) and endometrial cancer (EC).
METHODS All published studies on the association between PCOS and EC identified through MEDLINE (1966–April 2011), EMBASE (1980–April 2011) and Cochrane (1998–April 2011). Original data were abstracted where available and summarized on a separate Microsoft Excel (2007) database for analysis. A total of 14 studies comparative and non-comparative were identified and included.
RESULTS The non-comparative and comparative data suggested that women with PCOS were more likely to develop EC. A meta-analyses of five comparative studies showed an increased risk of EC in women with an odds ratio of 2.89 with a 95% confidence interval of 1.52–5.48.
CONCLUSIONS Women with PCOS are about three times more likely to develop EC compared with women without it. This translates into a 9% lifetime risk of EC in Caucasian women with PCOS compared with 3% in women without it. Although most women (91%) with PCOS will not develop endometrial cancer, our study has shown that they are more likely at increased risk. More studies are required to clarify the exact molecular mechanisms, determine the best way of screening and preventing disease progression.

Introduction

Polycystic ovarian syndrome (PCOS) is the most common endocrine disease affecting women of reproductive age of whom ~5–10% have the syndrome. The aetiology is uncertain and because of its heterogeneity different groups classify PCOS differently. In 2003, an international consensus group proposed that PCOS should be diagnosed in women with at least two of the following present: oligomenorrhea or amenorrhea, hyperandrogenemia and polycystic ovaries defined by ultrasonography after exclusion of other medical conditions that cause irregular menstrual cycles and androgen excess (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2003). Endometrial cancer (EC) is the most common female genital tract malignancy in most countries affecting 2–3% of women (mostly post-menopausal; Parker et al., 1997; National Cancer Institute of Canada, 2003). Usually, the prognosis of EC is good with an overall survival rate of 80% because the majority of cases are diagnosed at an early stage (Markman, 2005). There are two major histological types of EC: Type 1 or endometrioid endometrial cancer (EEC), accounting for >75% of EC cases and Type 2, non-EEC (Sherman, 2000). There is currently no effective screening programme for EC and, in the UK, cases are mostly diagnosed following investigations including transvaginal ultrasound, pipelle biopsy and hysteroscopy in women who present most commonly with bleeding per vaginum (intermenstrual, post-menopausal or heavy menstrual).

Women with PCOS have several risk factors for EC and may be at increased risk of developing EC (Hardiman et al., 2003). Some of the clinical, metabolic and molecular risk factors include unopposed estrogen stimulation of the endometrium in anovulatory PCOS women, obesity, insulin resistance, insulin like growth factors, diabetes, nulliparity, Cyclin D1, gluthathione-S-transferase and progesterone resistance (Hardiman et al., 2003; Pillay et al., 2006; Atiomo et al., 2009). The exact strength of the association between PCOS and EC is however unclear and an article published in the Lancet in 2003 (Hardiman et al., 2003) concluded that the evidence for an increased risk of endometrial carcinoma in PCOS was incomplete and contradictory. However, a recently published systematic review (Chittenden et al., 2009) showed in a meta-analysis that women with PCOS were almost three times more likely to develop EC with an odds ratio (OR) of 2.70 and a confidence interval (CI) of 1–7.29 (no difference to a 7.29 increased risk). A closer inspection of the data used in the meta-analysis however 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. These data therefore suggested that there was still some uncertainty about the exact strength of the association between EC and PCOS.

The aim of this study therefore was to further investigate the exact strength of the association between PCOS and EC by carrying out an updated and independent systematic review and meta-analysis. This was thought to be an important research question because of the implications for clinical management and research including the need to incorporate clear surveillance and clinical prevention strategies for EC in women with PCOS was found to be at increased risk.

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