Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less than 50 years: An Australian case-control study
School of Population Health, The University of Queensland, Herston Road, Herston, QLD 4006, Australia. Cancer Causes and Control
(Impact Factor: 2.74).
10/2010; 21(12):2303-8. DOI: 10.1007/s10552-010-9658-7
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.
Available from: James E Klaunig
- "Among younger women who are diagnosed with endometrioid endometrial adenocarcinoma, chronic disorders of ovulation are common (Navaratnarajah et al., 2008). An Australian study of women younger than 50 with a diagnoses of endometrial adenocarcinoma found an increased likelihood that affected women reported a diagnosis of polycystic ovarian syndrome (PCOS) or symptoms of chronic oligo/anovulation (irregular menses, severe acne as an adult, hirsuitism), odds ratio 4.3, 95% confidence interval 1.8e10.2 in comparison to a control group without endometrial adenocarcinoma (Fearnley et al., 2010). A typical feature of PCOS is irregular or absent ovulation with prolonged exposure of the endometrium to the proliferative effects of ovarian estrogen without the counterbalancing effects of luteal progesterone. "
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ABSTRACT: Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production and formulation of consumer products with potential exposure to manufacturing workers, consumer, and the general public. Following a combined 2-year inhalation chronic bioassay performed in Fischer 344 (F344) rats, an increase in uterine endometrial adenocarcinomas was noted at the highest concentration to which animals were exposed. No other neoplasms were detected. In this study, a dose of 160 ppm produced an incidence of 8% endometrial adenocarcinomas. Based on a number of experimental studies with D5, the current manuscript examines the biological relevance and possible modes of action for the uterine endometrial adenocarcinomas observed in the rat following chronic exposure to D5. Variable rates of spontaneous uterine endometrial adenocarcinomas have been reported for untreated F344 CrlBr rats. As such, we concluded that the slight increase in uterine endometrial adenocarcinomas observed in the D5 chronic bioassay might not be the result of D5 exposure but may be related to variability of the spontaneous tumor incidence in this strain of rat. However, if the uterine endometrial adenocarcinomas are related to D5-exposure, alteration in the estrous cycle in the aging F344 rat is the most likely mode of action. D5 is not genotoxic or estrogenic. The alteration in the estrous cycle is caused by a decrease in progesterone with an increase in the estrogen:progesterone ratio most likely induced by a decrease in prolactin concentration. Available data support that exposure to D5 influences prolactin concentration. Although the effects on prolactin concentrations in a number of experiments were not always consistent, the available data support the conclusion that D5 is acting via a dopamine receptor agonist-like mechanism to alter the pituitary control of the estrous cycle. In further support of this mode of action, studies in F344 aged animals showed that the effects of D5 on estrous cyclicity produced a response consistent with a dopamine-like effect and further suggest that D5 is accelerating the aging of the reproductive endocrine system in the F344 rat utilized in this study. This mode of action for uterine endometrial adenocarcinoma tumorigenesis is not relevant for humans.
Copyright © 2015. Published by Elsevier Inc.
Available from: Ruijin Shao
- "In the clinic, EC is usually preceded by, or associated with, endometrial hyperplasia , which is a proliferative process that results in an increased ratio of epithelial cells to stromal components in the endometrium . Endometrial hyperplasia predisposes for the development of EC, and a case–control study showed that women with PCOS and endometrial hyperplasia have a four times greater risk of developing EC than non-PCOS women . PCOS is a hyperandrogenic state that results in increased bioavailability of unopposed estrogens due to the increased peripheral conversion of endogenous androgens such as testosterone and androstenedione into estrogen [13,15]. "
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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.
Available from: Philippa T K Saunders
- "PCOS and EC share many of the same risk factors and a recent population-based case-control study in 135 Australia found that women with PCOS have a four-fold increased risk of EC compared to women without PCOS (Fearnley, et al. 2010). This risk was elevated for type 1 cancers and had a greater association with symptoms of androgen excess such as hirsutism (OR 2.4, all EC cases) and irregular periods (OR 3.1, all EC cases) (Fearnley et al. 2010). "
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ABSTRACT: Endometrial and ovarian cancers are common gynecological malignancies. The impact of androgen action in these cancers is poorly understood however there is emerging evidence to suggest that targeting androgen signalling may be of therapeutic benefit. Epidemiological evidence suggests that there is an increased risk of endometrial cancer associated with exposure to elevated levels of androgens and genetic variants in genes related to both androgen biosynthesis and action are associated with increased risk of both endometrial and ovarian cancer. Androgen receptors may be a potential therapeutic target in endometrial cancer due to reported anti-proliferative activities of androgens. In contrast, androgens may promote growth of some ovarian cancers and anti-androgen therapy has been proposed. Introduction of new therapies targeting androgen receptors expressed in endometrial or ovarian cancers will require a much greater understanding of the impacts of cell context-specific androgen receptor-dependent signalling and how androgen receptors can cross-talk with other steroid receptors during progression of disease. This review considers the evidence that androgens may be important in the aetiology of endometrial and ovarian cancers with discussion of evidence for androgen action in normal and malignant endometrial and ovarian tissue.
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