Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less than 50 years: an Australian case-control study.
ABSTRACT Although polycystic ovary syndrome (PCOS) is commonly cited as a risk factor for endometrial cancer, supporting epidemiological evidence is currently very limited. Our aim was to assess the associations between PCOS, PCOS symptoms, and risk of endometrial cancer in women aged less than 50 years.
Data came from a national population-based case-control study in Australia. Cases with newly diagnosed histologically confirmed endometrial cancer were identified through treatment clinics and cancer registries Australia wide. Controls were randomly selected from the national electoral roll. Women were interviewed about their reproductive and medical history, including self-reported PCOS, and lifestyle. Current analyses were restricted to women aged under 50 (156 cases, 398 controls). We estimated odds ratios (OR) using logistic regression to adjust for confounding factors.
Women with PCOS had a fourfold increased risk of endometrial cancer compared to women without PCOS (OR 4.0, 95% CI 1.7-9.3). This association was attenuated when additionally adjusted for body mass index (OR 2.2, 95% CI 0.9-5.7). Risk was slightly greater when restricted to Type I cancers. PCOS symptoms including hirsutism and very irregular periods were significantly associated with endometrial cancer risk.
These data extend existing findings, including adjustment for confounders, suggesting PCOS is a risk factor for endometrial cancer.
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ABSTRACT: To review recent studies about the application of aromatase inhibitors in endometrial carcinoma and the benefits and challenges of aromatase inhibitors in this regard. Relevant studies and manuscripts were searched on Pubmed using the following terms, either alone or in combination: aromatase, aromatase inhibitors, letrozole, anastrozole, endometrial cancer, breast cancer, endocrine, therapy, and side effects. Endometrial carcinoma is one of the most pervasive gynecological malignancies. Type I endometrial carcinoma is estrogen-dependent. Recent studies have demonstrated that aromatase inhibitors, which interfere with estrogen biosynthesis by inhibiting the activity of aromatase, can be used to treat endometrial carcinoma and its precancerous lesions to some extent. In early-stage endometrial carcinoma or atypical hyperplasia, a precancerous lesion of endometrial carcinoma, the effects of aromatase inhibitors were promising. However, in advanced or recurrent endometrial carcinoma, the application of aromatase inhibitors cannot solve the problem evidently. In addition, these inhibitors have limitations, like side effects and drug resistance. The need for a new generation of inhibitors with higher specificity and fewer side effects should be studied further. Aromatase inhibitors show promise in the therapy of endometrial carcinoma, especially the early stage. Further studies should be conducted to develop next-generation aromatase inhibitors with higher specificity and fewer side effects.Gynecologic Oncology 05/2014; · 3.93 Impact Factor
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ABSTRACT: BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women.METHODS We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated.RESULTSFrom 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P < 0.008), but the risk of ovarian and breast cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P < 0.11 and OR, 0.95; 95% CI, 0.64-1.39, P < 0.78, respectively). However when studies which included women aged over 54 years were excluded from the analysis, the risk for women with PCOS increased further for endometrial cancer (OR, 4.05; 95% CI, 2.42-6.76, P < 0.00001), became significantly increased for ovarian cancer (OR, 2.52; 95% CI, 1.08-5.89, P < 0.03), but remained non-significant for breast cancer (OR, 0.78; 95% CI, 0.46-1.32, P < 0.35).CONCLUSIONS This is the first meta-analysis to examine gynaecological cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias in the studies may have resulted in an exaggeration of the increased risk. Furthermore, women who have PCOS should also be made aware that any increased risk for endometrial cancer must be judged in the context of its relatively low incidence in the general population. A large well-controlled prospective study is required in order to gain a more accurate estimate of the risk of gynaecological cancers in women with PCOS.PROSPERO CRD REGISTRATION NUMBERCRD42012003500.Human Reproduction Update 03/2014; · 9.23 Impact Factor
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ABSTRACT: Although a number of in vitro studies have demonstrated the antiproliferative, anti-invasive, and antimetastatic effects of metformin in multiple cancer cell types, its cellular and molecular mechanisms of anti-cancer action in the endometrium of women with polycystic ovary syndrome (PCOS) have not yet been fully elucidated. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are known to be involved in metformin uptake and excretion in cells. In this article, we discuss the novel therapeutic possibilities for early-stage endometrial carcinoma (EC) in women with PCOS focusing on metformin, which might have a direct effect in the endometrium through the OCTs and MATEs. We then review the molecular mechanism(s) of the action of metformin in the endometrium and highlight possible mechanistic insights into the inhibition of cell proliferation and tumor growth and, ultimately, the reversal of early-stage EC into normal endometria in women with PCOS.Journal of experimental & clinical cancer research : CR. 05/2014; 33(1):41.