Early menarche is associated with 1.5–4-fold increased risk of endometrial cancer [4, 5]. Early menarche was identified as a risk factor for endometrial cancer among Turkish women [6] and late menarche as a protective factor in the European Prospective Investigation into Cancer and Nutrition (EPIC) [7]. Also, a reduction in endometrial cancer risk was observed in women with early menopause in the EPIC study [7]. Menstrual span of more than 39 years was associated with 4.2 times higher risk than one with less than 25 years [8].

Lower parity has been identified as a risk factor for endometrial cancer [6] and high parity as a protective factor [7]. Parity, age at first birth, age at last birth and time since last birth are highly correlated. It is difficult to separate their independent effects, although some studies have shown that late age at last childbirth reduces the risk of endometrial cancer [9, 10]. A study from Norway shows that the risk of endometrial carcinoma decreased significantly with increasing parity as well as with increasing age at first and last birth [11].

Pregnancy acts as a protective factor [2]. Decreased risk of endometrial cancer was associated with cumulative duration of full-term pregnancy (FTP) [7].

Studies done so far report contradictory findings regarding the association between spontaneous and induced abortion with risk of endometrial cancer. In comparison with women reporting no induced abortion, the odds ratio (OR) of endometrial cancer was 0.6 in women reporting one and 0.4 in those reporting two or more induced abortion [10]. Certain conditions like Stein–Leventhal syndrome characterized by accumulation of incompletely developed follicles in the ovaries have been linked to endometrial cancer [12].

Oral contraceptive use lowers the risk of endometrial cancer [7] with the lowest risk observed in women taking pills for a long time [2]. Combined oral contraception has shown to have a protective effect ranging from less than 5 years to greater than 15 years after cessation of the pills [13].

A nationwide, population-based case–control study among postmenopausal women aged 50–74 years in Sweden shows that oral contraceptives decrease the risk for endometrial cancer by 30 %, while progestin-only pills reduced the risk more markedly. Reduction in the risk was noticeable following 3 or more years of use for combined oral contraceptives and increased with duration of intake, reaching 80 % lower risk after 10 years of use. The protection remained for at least 20 years after cessation of use [14].

Theoretically, IUD use may decrease endometrial cancer risk through at least two mechanisms: Intrauterine devices act as protective factor through either one of the following mechanisms. IUDs may exert an intense inflammatory response leading to other lysosomal and inflammatory actions including recruitment of cells responsible for early elimination of abnormal, precancerous, hyperplastic endometrial epithelial cells. IUDs may induce changes in endometrial environment and endometrial response to hormones leading to more complete shedding of the endometrium, thereby decreasing chances of endometrial hyperplasia which is a known risk factor for endometrial carcinoma [15]. The meta-analysis by Beining RM found a protective association among women who reported ever use of an intrauterine device and risk of endometrial cancer [16].

Women with polycystic ovarian syndrome (PCOS) have a 2.7-fold increased risk for developing endometrial cancer, most of which are well-differentiated tumours with good prognosis. The link between PCOS and endometrial cancer involves prolonged endometrial exposure to unopposed oestrogen due to anovulation and endometrial progesterone resistance. This is accompanied by several gene abnormalities controlling progesterone action and cell proliferation [17].

There is strong evidence suggesting oestrogen therapy unopposed by progesterone therapy is a major risk factor for endometrial cancer in women with an intact uterus, with the risk substantially increasing with current, long-duration use [18].

Many studies show that women taking combination of oestrogen–progesterone therapy exhibit a similar risk to women who do not take postmenopausal hormone therapy. However, a meta-analysis including ten case–control studies and one cohort study calculated a significant reduction of risk, with a relative risk (RR) of 0.44, 0.33 and 0.28 after 4, 8 and 12 years of combined oral contraceptive (COC) use, respectively. This was based on 33 time-dependent estimates of RR, adjusted for age, adiposity, parity and use of oestrogen replacement therapy [19].

It is now considered that risk varies with specific categories of oestrogen plus progestin usage, like the use of long duration of sequential progestins increases the risk, whereas decreased risk is observed for users of short-duration continuous progestins. Higher risk noted among thin to normal-weight women could indicate that there is an endogenous oestrogen threshold beyond which exogenous oestrogen exposures fail to increase the risk [18].

HRT use was identified as a risk factor for endometrial cancer among Turkish women [6]. Oestrogen-only HRT substantially increases the risk of endometrial cancer in women with a uterus [20].

Tamoxifen is one of the selective oestrogen receptor modulators (SERMs) and has primarily antioestrogenic properties in the breast tissue. However, it also has modest estrogenic activity and hence is found to be associated with endometrial carcinoma. There is an increasing risk of endometrial cancer associated with longer tamoxifen treatment, extending well beyond 5 years which does not diminish in follow-up to at least 5 years after the end of the last treatment [21].

In the Israel national breast cancer cohort, tamoxifen use was associated with elevated risks of uterine cancer incidence and mortality [22].

A population-based study of women with endometrial hyperplasia, who remained at risk for at least 1 year, indicates that the overall progression risk for endometrial hyperplasia is three times higher than the average population risk of endometrial carcinoma. Fewer than 5 % of women with non-atypical or simple endometrial hyperplasia will experience progression to carcinoma, but 28 % of women with atypical hyperplasia will progress to carcinoma during 20 years [23].

Women diagnosed with breast cancer have a higher incidence of second primary cancers, particularly of endometrial cancer in women over 50 at diagnosis [24]. The granulosa–theca cell tumour of the ovary secretes oestrogen, which is uncontrolled, and this can sometimes lead to high oestrogen levels, leading to stimulation of the endometrium and resulting in endometrial cancer [2].

This disorder is commonly caused by a defect in either the gene MLH1 or the gene MSH2. Defects in other genes can also cause HNPCC, namely, MLH3, MSH6, TGBR2, PMS1 and PMS2, and increase the risk of endometrial cancer [2].

The risk of endometrial cancers has been recorded as high among obese women [18]. Endometrial cancer is twice as common in overweight women and more than three times as common in obese women.

Endometrial cancer is inversely related to the age at menarche and directly related to the age at menopause. Women with higher BMI tend to be younger at menarche than the ones with lower BMI, and conversely, women with higher BMI tend to be older at menopause than women with lower BMI [25]. Some studies suggest that the association between high BMI and endometrial cancer is stronger in postmenopausal women than in premenopausal women [26]. This indicates that obesity may have a continuous and cumulative effect on the development of endometrial cancer [27].

McCullough et al. in their prospective cohort found adult body mass index (BMI) as a strong predictor of risk. The use of oestrogen plus progestin postmenopausal hormone therapy modified the association. Among never users, risk was significantly linear across the entire range of BMI examined, but among ever oestrogen plus progestin users, the association was not significant. No difference in risk was observed according to the tendency for central versus peripheral fat deposition [28]. Weight gain and lack of weight stability are associated with risk of endometrial cancer [29].

Adiposity causes an increase in the frequency of anovulatory and irregular menstrual cycles, resulting in the reduction of luteal phase progesterone levels and ultimately increased exposure to unopposed oestrogen, thus explaining the increased risk of endometrial cancer in younger women [30, 31]. Obesity in postmenopausal women is associated with excess aromatization of androgen into oestrogen in the adipose tissue and lowered circulating sex hormone-binding globulin [32].

Excessive sitting time is associated with an increased endometrial cancer risk, independent of the level of moderate–vigorous physical activity. Physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30–33 % lower risk than inactive women [33]. In addition, consistent overweight or obesity during adulthood was associated with greater risk of endometrial cancer than being overweight or obese only in later adult life.

Percent energy from fat was associated with an increased risk of endometrial cancer, with saturated and monounsaturated fats being the main contributors of risk. A number of studies have concluded that diets rich in fat and poor in complex carbohydrates and fibre are associated with increased risk of endometrial cancer, while some studies have shown independent association between the two after adjusting for BMI and total energy intake [34, 35]. There was a stronger association between dietary fat and endometrial cancer among groups with higher circulating oestrogen levels [36].

Hypertension was identified as a risk factor for endometrial cancer in studies conducted in women in Finland as well as in Turkey [37, 6].

The risk of endometrial cancer is high among women with diabetes. High glucose levels increases the risk by providing energy for proliferation of cells, generating free radicals causing damage to DNA and DNA repair enzymes [38, 39].

A meta-analysis of cohort studies suggests significant association between diabetes mellitus and increased risk of incidence of endometrial cancer but no increased risk of mortality due to endometrial cancers [40]. Another meta-analysis involving both case–control and cohort studies found diabetes to be statistically significantly associated with an increased risk of endometrial cancer with the risk estimates being somewhat stronger for case–control studies [41]. Diabetes was identified as a strong risk factor for endometrial cancer in a nationwide record-linkage study in Finland [37] and among Turkish women [6]. Diabetes was associated with a twofold increased risk, and combination of diabetes with obesity and low physical activity was associated with a further increased risk for endometrial cancer [42].