The key to endometrial function lies in the effects of oestrogen and progesterone on the endometrium, enabling it to progress through the normal menstrual cycle and to prepare for embryo implantation. Oestrogen stimulates proliferation in the glands and stroma. Progesterone inhibits mitotic activity and stimulates secretion in the glands and decidualization of the stroma, where the cells acquire more cytoplasm. It is therefore perhaps not surprising that unopposed oestrogens will promote continuous mitotic activity, leading to cancers, whilst progestogens provide some protective effect. Thus high oestrogen levels, whether endogenous or exogenous, and low progestogen levels are risk factors for endometrial cancer. High endogenous oestrogen levels can occur because of increased aromatization of androgens to oestrogens. Thus, endometrial cancer is 10 times more common in obese women because the peripheral conversion of androstenedione to oestrone happens in the adipose tissue. Exogenous oestrogens also increase the risk of endometrial cancer. The use of unopposed oestrogens carries a fourfold to eightfold relative risk, especially in hormone replacement therapy (HRT), which is abrogated almost completely by combining progesterone with oestrogen. A great deal of attention has been paid to the induction of endometrial cancer by tamoxifen and has led to the development of new selective oestrogen receptor modulators, including raloxifene. Although the benefit of tamoxifen therapy for breast cancer outweighs the potential increase in endometrial cancer, the relative risk is sixfold to sevenfold. Screening for endometrial cancer in women with breast cancer, taking tamoxifen, has no proven benefit, but abnormal bleeding should prompt rapid investigation. Low progestogen levels are also a risk factor for the development of endometrial cancer and occur with the polycystic ovarian syndrome (Stein–Leventhal syndrome) as well as early menarche, late menopause and nulliparity.

Endometrial cancer rarely develops before the menopause, and, since it causes abnormal vaginal bleeding, it can usually be diagnosed at an early stage. Postmenopausal bleeding is always abnormal and requires prompt investigation. Hysteroscopy, which allows visual inspection of the uterine lining, is often used for diagnosis and can detect abnormalities in 95–100% of cases. The probability of endometrial cancer among women with postmenopausal bleeding who do not use HRT is 10%. If the transvaginal ultrasound scan is normal, this probability falls to 1%, so ultrasound allows the majority of women to be quickly reassured. Outpatient endometrial biopsy methods are now as accurate as dilatation and curettage (D&C), which requires a general anaesthetic.

The optimum treatment for endometrial cancer depends on the stage and grade of the disease and on the risk of tumour in lymph nodes. When the cancer is confined to the inner half of the myometrium (stage IA and IB), the lymph nodes are likely to be clear and total hysterectomy is usually sufficient as treatment. This applies to about 70% of women with endometrial cancer, and their 5-year survival exceeds 85%. Surgical colleagues are inclined to eagerness to wield their scalpels, but they should be dissuaded from proceeding to lymphadenectomy. A recent Cochrane analysis has shown an increase in morbidity with no survival benefit. In women with tumour that extends beyond the inner half of the myometrium or with regional lymph node involvement, adjuvant pelvic radiotherapy is widely used. This has been shown to reduce the rate of local recurrence but may have long-term sequelae, including lymphoedema. Radiotherapy is also valuable in the management of pelvic recurrence and in palliating bone metastases. Extrapelvic disease and distant metastases may be treated with platin-based combination chemotherapy or endocrine treatment.

Case Study: The headmistress’ family.