The exact cause of the disease is unknown but the following associations have been identified as risk factors:
- endogenous risk factors
- increasing age
- obesity and physical inactivity
- early menarche and late menopause
- low parity or infertility
- polycystic ovarian syndrome
- family history
- lynch syndrome (hereditary nonpolyposis colorectal cancer)
- oestrogen secreting tumours (granulosa or thecal cell tumours of ovary)
- diabetes mellitus
- hypertension
- history of breast cancer
- immunodeficiency
- exogenous risk factors
- unopposed oestrogen only hormone replacement therapy
- tamoxifen therapy
- dietary factors
- previous radiotherapy
An excess of oestrogen is common to all risk factors:
- in obese patients, androstenedione is converted to oestrone in adipose tissue
- a late menopause is preceded by many anovulatory cycles resulting in a lack of progesterone to counter the endometrial proliferation mediated by oestrogens
- patients with polycystic ovary disease have anovulatory cycles
- ovarian theca cell tumours produce oestrogens
The following are thought to have a protective effect against endometrial carcinoma:
- cigarette smoking
- combined oral contraception for at least one year - reduces the incidence in pre and peri menopausal women
- grand multiparity
In endometrial hyperplasia (a premalignant condition of endometrial carcinoma), excess unopposed oestrogen acts as a recognized risk factor.
- in 30-40% of patients with atypical hyperplasia will have a concurrent adenocarcinoma while the rest are at very high risk of developing the cancer.
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