aetiology

Last reviewed 04/2023

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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