Endometrial risk factors

The pattern of hormonal risk factors involved in the development of endometrial cancer is similar to those associated with the development of breast cancer. In addition, there is substantial evidence to suggest that HRT can increase the risk (Beral et al, 1999 Bingham et al, 1998). Compared to the UK, the incidence of endometrial cancer in countries such as Japan is relatively low (Bingham et al, 1998). It has been suggested that dietary factors may be responsible for the reduced incidence, and there is indirect evidence from epidemiology studies which suggests that increased consumption of soy products may lower the risk of endometrial cancer. However, these data are not conclusive. To date, no studies have demonstrated a link between consumption of phytoestrogens and an increased risk of endometrial cancer. 

The clinical problems that arise in the menopause are hot flushes, sweating, depression, decreased libido, increased risk of cardiovascular disease and osteoporosis. The latter results in increased incidence of hip, radial and vertebral fractures. Oestrogen is one factor controlling synthesis of active vitamin D and osteoporosis is in part due to a deficiency of vitamin D. Not surprisingly, to reduce these problems, administration of oestrogen is recommended (known as hormone replacement therapy or HRT). HRT reduces some of the risk factors for coronary artery disease since it reduces blood pressure and decreases the blood level of LDL-cholesterol and increases that of HDL-cholesterol. However, there is considerable debate about whether HRT increases the risk of breast or endometrial cancer. 

In untreated women, the main risk factors for endometrial carcinoma are age, obesity, nulliparity, late menopause (and possibly early menarche), the Stein-Leventhal syndrome, exposure to exogenous estrogens, radiation, and certain systemic diseases, including diabetes mellitus, hypertension, hypothyroidism, and arthritis (SED-14, 1451) (88). Certain of these risk factors indicate that an altered endocrine state with increased estrogen stimulation is a predisposing cause, and one might thus in theory expect estrogen treatment (and notably hormonal replacement therapy) to increase the risk (SEDA-22, 466). 

While the risk that hormone replacement therapy may cause endometrial tumors has been widely discussed, less attention has been given to the possibility that it could increase the risk of epithelial ovarian cancer. Since cancer of the ovary has some risk factors in common with endometrial cancer (notably low parity and obesity), this possible risk needs to be considered, especially in view of the fact that the endometrioid epithelial type of ovarian tumor is histologically so similar to adenocarcinoma of the endometrium. 

Cohen I, Azaria R, Bernheim J, Shapira J, Beyth Y. Risk factors of endometrial polyps resected from postmenopausal patients with breast carcinoma treated with tamoxifen. Cancer 2001 92(5) 1151-5. 

The current consensus is that the contemporary low-dose preparations pose minimal risks in women who have no predisposing risk factors and, in fact, may provide certain beneficial health effects (e.g., protection against endometrial and ovarian cancer). Oral contraceptive pills have been associated with increased risk for myocardial infarction, stroke, and venous thromboembolism. However, studies have been published that suggest that these risks are minimal in appropriately chosen low-risk women. 

The risks and benefits of HRT should be carefully assessed on an individual basis. This is particularly important in women with predisposing risk factors, such as a personal or family history of deep vein thrombosis or pulmonary embolism, severe varicose veins, obesity or prolonged bed-rest [2], because HRT increases the risk of venous thromboembolism and stroke. HRT has also been observed to increase the risk of gallbladder disease, breast cancer and endometrial cancer. It is recommended that the minimum effective dose should be used for the shortest period of time, with treatment being reviewed at least once a year [2]. 

In secondary prevention the patient has the disease and the objective is to reduce risk factors and to retard progression (e.g. aspirin and lipid-lowering drugs in atherosclerosis and post-myocardial infarction). In breast cancer, the use of tamoxifen, which can itself rarely cause endometrial cancer (which is detectable and treatable), raises complex scientific and socioeconomic issues. 

Women with or at risk for hereditary nonpolyposis colon cancer should begin annual endometrial biopsy starting at age 35. To include examination for cancers of the mouth, thyroid, testicles, skin, lymph nodes, and ovaries, as well as health counseling about tobacco, sun exposure, diet and nutrition, risk factors, sexual practices, and environmental and occupational exposures. From The American Cancer Society. ... 

Exposure to unopposed oestrogens is a risk factor for endometrial carcinoma. Unopposed oestrogens should no longer be used to treat postmenopausal symptoms in women who have not had hysterectomy. Excessive fat consumption and overweight [defined as a body-mass index (BMI) of at least 25 kg/m j are important risk factors present in almost 50% of women with endometrial cancer [7,26] (see Table 6.2). 

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