Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Abstract

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full‐term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7–8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

Reproductive and hormone‐related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort

“…19 These analyses included ages at menarche and menopause, duration of OC use, and duration of full-term pregnancies (number of full-term pregnancies *0.75), mutually adjusted and as a composite variable to estimate total duration of ovulatory lifespan. We further examined associations between number of full-term pregnancies, age at first and last pregnancy, and time since last pregnancy in mutually adjusted models investigating risk associations among parous women.…”

“…Findings for endometrioid tumors are consistent with prior data linking older age at menopause with increased risk of both endometrioid EOC 10 and endometrial carcinoma. 19,25 Recent investigations in large, wellcharacterized cohorts suggest parity 9 and breastfeeding 10 may differentially impact risk by histologic subtype. We did not observe heterogeneity by either of these factors, though breastfeeding was suggestively inversely associated with serous tumors.…”

An epidemiological model for prediction of endometrial cancer risk in Europe

“…Although EC is frequently diagnosed at an early stage when the disease is curable, about one fifth of all cases have a poor prognosis (1). Well-established risk factors for EC include obesity, use of estrogen-only hormone replacement therapy (HRT) and polycystic ovary syndrome, whereas the use of combined estrogen-plus-progestin HRT and oral contraceptives (OC) are protective (2)(3)(4)(5)(6)(7)(8). As the number of women living to an older age is steadily growing, together with the prevalence of obesity and sedentary lifestyles, the number of EC cases is also expected to increase in the near future (9).…”

A Review of Recent Findings for Obstetricians about Combined Oral Contraceptive Pills

“…This protective effect is especially evident in nulliparous women, breast cancer (BRCA) gene I and II carriers, and those with a positive family history. According to the conducted studies, the rate of epithelial cancer and borderline tumors reduces following the consumption of OCPs (26). However, the mechanism of oral contraceptives in the prevention of ovarian cancer is unknown, although induction of apoptosis may be one of the involved mechanisms (27,28).…”