COMMENTARY

Weight and the Risk for Endometrial Cancer in Young Women

Peter Kovacs, MD, PhD

Disclosures

September 11, 2009

Endometrial Cancer Risk Among Younger, Overweight Women

Thomas CC, Wingo PA, Dolan MS, Lee NC, Richardson LC
Obstet Gynecol. 2009;114:22-27

Background

Endometrial cancer is the most common gynecologic cancer among women 45 years of age and older, and it is the fourth most common cancer among women. There are various histologic types of endometrial cancer, and most cases are picked up at an early stage. Survival rates depend on the histologic type, differentiation, and stage of the disease. In early stage endometrial cancer, survival rates are in the excess of 90%.

Several risk factors are known for endometrial cancer: age, nulliparity, infertility, unopposed estrogen/tamoxifen use, obesity, hypertension, diabetes, and genetic predisposition. On the other hand, use of oral contraceptives and regular physical activity reduce the risk.[1] The most common presenting symptom is vaginal bleeding. Staging of the disease is made surgically. For early stage disease (ie, cancer that is localized to the endometrium), conservative therapy is possible, such as high-dose progestin therapy, polypectomy if the disease is confined to a polyp, or a simple hysterectomy.[2] Well-differentiated early stage disease is associated with excellent survival rates. In advanced cases, more extensive surgery is required, with a possible need for adjuvant therapy as well. Ultrasound and hysteroscopy are helpful in identifying patients at risk, and various biopsy methods are available to pick up the disease.

Although most cases of endometrial cancer occur in postmenopausal women, younger women who have been exposed to unopposed estrogen are at risk too. The first half of a normal menstrual cycle is characterized by proliferative changes, with estrogen as the main force. Following ovulation, mainly in response to progesterone, secretory changes are induced without further proliferation. If a patient is anovulatory, proliferation will continue without progesterone "control" and may lead to hyperplasia and even cancer. The various types of hyperplasia are simple hyperplasia, complex with atypia, and complex without atypia. Complex hyperplasia with atypia has a 25% risk of progressing to cancer if left untreated.[3] Obesity increases estrogen exposure, partly because it is frequently accompanied by anovulation. Additionally, aromatase in fat tissue leads to the conversion of androgen to estrogen. Lower sex hormone-binding globulin levels are also associated with an increased amount of free sex steroids.

Summary

This case-control study evaluated the risk for endometrial cancer among overweight women. The study population was the participants of the Cancer and Steroid Hormone Study. Women in the case group were between the ages of 20 and 54 and were diagnosed with endometrial cancer. Women in the control group were matched for geographic location, age, and time frame of cancer diagnosis. Weight was assessed using body mass index. Overweight was defined as a body mass index > 25 kg/m2, and obesity was defined as a body mass index > 30 kg/m2. Four patient categories were made: normal weight at age 18 and as an adult; normal weight at age 18 but overweight/obese as an adult; overweight/obese at age 18 and normal weight as an adult; overweight/obese at age 18 and as an adult. During the analysis, adjustments were made for age, use of oral contraceptive pills (OCP), education, parity, menopausal status, estrogen therapy, and blood pressure. In general, women in the case group were more likely to be older, nulliparous, never exposed to OCPs, postmenopausal, have high blood pressure, and be exposed to estrogen. Cases were also more likely to be overweight or obese at age 18, as an adult, or at both timepoints. Women who were of normal weight at age 18 but were overweight/obese as an adult had an increased risk for endometrial cancer (< 45 years, odds ratio 4.8; ≥ 45 years, odds ratio 1.8). Those who were overweight/obese at age 18 but had normal weight as an adult had no increased risk (< 45 years, odds ratio 0.6 not significant; ≥ 45 years, odds ratio 1.1 not significant). The greatest risk for endometrial cancer was among those who were overweight/obese at age 18 and as an adult as well (< 45 years, odds ratio 5.8; ≥ 45 years, odds ratio 1.9).

Viewpoint

Cancer is generally caused by hereditary and nonhereditary factors. Certain mutations put patients at risk for certain cancers (eg, BRCA mutation and breast cancer). Environmental factors are also associated with an increased incidence of special cancer types (eg, radiation and leukemia). Lifestyle factors can also increase the incidence of cancer (eg, smoking and lung cancer). Hereditary factors cannot be modified, but patients at risk could be screened and elective measures (eg, BRCA mutation and oophorectomy/mastectomy) can be used to minimize the risk. Lifestyle changes, however, can and should be modified to lower one's risk. Obesity is a known risk factor for several medical problems, one of which is endometrial cancer. Recommendations regarding lifestyle changes should be made as early as possible, especially in the case of young patients. Young, overweight/obese women are more likely to be anovulatory, are more likely to need evaluation for infertility, and are more likely to receive infertility therapy. The delay in childbearing or the inability to conceive will limit their exposure to other beneficial measures as well, such as OCP use. A very important finding of this study is that women who were overweight/obese at age 18 but were of normal weight as adults had no increased risk for endometrial cancer when compared with those who were of normal weight at both timepoints. Overweight women need to be counseled about appropriate diet, regular physical activity, and other medical and surgical interventions that can be used to lower weight. In many cases, this has to be a multidisciplinary effort. Patients who are unable to lose weight despite these efforts need to be regularly screened for morbidity associated with obesity (diabetes, cardiovascular disease, endometrial cancer, etc), as early detection and treatment significantly increases quality of life and survival.

Abstract

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