Endometrial cancer on the rise in older women (August 2014) Endometrial cancer incidence has been increasing among Ontario women aged 50–74 since 1995 and in those aged 75+ since 1981. Rising incidence likely reflects changes in the prevalence and distribution of risk factors for endometrial cancer, particularly hormone replacement therapy and obesity. Endometrial cancer incidence rates unadjusted for the proportion of women in the population who have had a hysterectomy underestimate the true incidence and may result in incorrect time trends for some age groups. Endometrial cancer incidence has been rising in Ontario women aged 50 years and older. After excluding women who had a hysterectomy (the surgical removal of the uterus) from the population at risk, endometrial cancer incidence rates in women aged 50–74 have increased at a rate of 0.7% per year since 1995, following a decline in the 1980s and early 1990s. In women aged 75 years and older, incidence rates have increased steadily at a rate of 1% per year since 1981. Women who have had a hysterectomy are no longer at risk for endometrial cancer and endometrial cancer rates that do not correct for these prior hysterectomies are too low. Because the proportion of women who have had a hysterectomy varies by age group and can vary over time, correcting for these procedures has a different impact on the trends in endometrial cancer incidence for different age groups. In Ontario women aged 50–74, for example, hysterectomy-corrected incidence rates for endometrial cancer are higher than the uncorrected rates but show a similar, although less striking, trend over time. In contrast, in women aged 75 and older, hysterectomy-corrected incidence rates are higher than the uncorrected rates, but show an opposite trend over time—between 1981 and 2009, the hysterectomy-uncorrected rates show a significant decrease. The most important risk factor for endometrial cancer is excess exposure to estrogens, relative to progesterone. Several reproductive and hormonal factors affect endometrial cancer risk by increasing or decreasing a woman’s exposure to estrogen. Examples of factors that affect this estrogen–progesterone balance include having more children, using combined oral contraceptives, and experiencing late menarche (onset of menstrual periods), which protect against endometrial cancer, and late menopause, which increases risk.1 Hormone replacement therapy (HRT) is another risk factor for endometrial cancer, although the relationship is complex. Using estrogen-only HRT increases risk, while combination progesterone–estrogen HRT reduces the risk of estrogen-induced endometrial cancer1 and may even protect against future endometrial cancer risk, depending on the preparation and duration of use.1,2 Through a mechanism related to greater estrogen production, being overweight or obese also increases the risk of endometrial cancer in women who have never used HRT.1   Increasing incidence of endometrial cancer in Ontario women older than 50 is consistent with patterns observed in other countries3 and likely reflects changing prevalence of risk factors, in particular the rising rates of obesity over several decades. Changing prevalence of the overall use of HRT and changes in the distribution of HRT types may also play a role. Following the 2002 publication of the Women’s Health Initiative study findings, which showed an increased risk of breast cancer and other adverse events associated with HRT use,4 HRT use declined rapidly and a corresponding decline in breast cancer incidence was observed in Canada.5 Because of the complex relationship between HRT and endometrial cancer, and a lack of detailed population-based data on the prevalence and type of HRT used in Ontario, it is difficult to determine and quantify the impact of HRT use on endometrial cancer incidence trends. However, given the continued increase in obesity and a potential lag time between HRT use and the development of endometrial cancer, it will be important to continue monitoring the hysterectomy-corrected incidence rate of endometrial cancer among Ontario women. References: Cancer Care Ontario. Cancer Risk Factors in Ontario: Evidence Summary. Toronto, Canada, 2013. Available at www.cancercare.on.ca/riskfactor. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013; 10(13):1353–68. Wartko P, Sherman ME, Yang HP, et al. Recent changes in endometrial cancer trends among menopausal-age US women. Cancer Epidemiol. 2013;37:374–7. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288(3):321–33. De P, Neutel CI, Olivotto I, Morrison H. Breast Cancer Incidence and Hormone Replacement Therapy in Canada. JNCI. 2010;102(19):1489–95. Citation: Cancer Care Ontario. Cancer Fact: Endometrial cancer on the rise in older women. August 2014. Available at http://www.cancercare.on.ca/cancerfacts. Prepared by staff in Prevention and Cancer Control.