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: 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.
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ABSTRACT: Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial cancer (EC). There is an urgent need for non-surgical prevention and treatment strategies for these patients who fail to respond to progesterone treatment and wish to preserve their fertility. Recently, we have reported that the combined treatment with metformin and progesterone-based oral contraceptives has successfully reversed the early-stage EC into normal endometria in addition to improvement of insulin resistance in women with PCOS. More importantly, one of these treated women has successfully delivered a healthy newborn baby. However, before such treatment can be recommended to the clinical practice, the molecular basis of metformin in the endometrium under physiological and pathological conditions must be elucidated.BBA Clinical. 12/2014;
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ABSTRACT: Women with Polycystic Ovary Syndrome (PCOS) show high prevalence of endometrial hyperplasia and adenocarcinoma. Endometrial proliferation is increased, evaluated by high levels of Ki67 (cell cycle marker) and low levels of p27 (negative regulator of cell cycle). Nevertheless, endometrial changes in cyclin D1 (positive regulator of cell cycle) in PCOS-women are not described. Androst-5-ene-3β,17β-diol (androstenediol), steroid with estrogenic activity present in endometria, could be related to increased endometrial cell proliferation. The objective of this study was to determine protein content of cyclin D1 and androstenediol levels in endometria from PCOS and control-women and to evaluate the possible mechanism favoring cell proliferation associated with hormonal characteristics of patients. Therefore, cyclin D1 protein content in PCOS-women and control-endometrial tissue were assessed by western blot and immunohistochemistry. The androstenediol levels were evaluated by ELISA. To further analyze the effect of steroids (androstenediol, 17β-estradiol, testosterone) in cell proliferation, levels of proteins cyclin D1, p27 and Ki67 were evaluated in an in vitro model of stromal endometrial cells T-HESC and St-T1b. An increase in cyclin D1 and androstenediol was observed in tissues from PCOS-women relative to control group (p<0.05). In the in vitro model, androstenediol exerted increase in cyclin D1 (p<0.05) and a decrease in p27 protein level (p<0.05), while Ki67 in St-T1b cells increased under this stimulus (p<0.05). Testosterone produces opposite effects in the levels of the above markers (p<0.05). Therefore, the hormonal imbalance associated with this syndrome could alter endometrial tissue homeostasis, promoting cell proliferation. Androstenediol is a molecule that could be involved by stimulating proliferation, whereas testosterone elicits a role of cell cycle repressor.Steroids 07/2014; · 2.80 Impact Factor