Aetiology

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.

Reference:

• (1) Saso S et al. Endometrial cancer. BMJ. 2011;343:d3954