Unopposed oestrogen as the main risk factor for endometrial cancer
The common type of endometrial cancer, a cancer of the endometrium (the inner lining of the uterus), is stimulated by oestrogen acting without enough progesterone to oppose it.
Remember
The central risk of the common type of endometrial cancer is oestrogen acting without enough progesterone to balance it, so anything that adds oestrogen without enough progesterone raises the risk.
Memory aid
Think of oestrogen as the accelerator and progesterone as the brake.
The risk rises when the accelerator is pressed for years with no brake.
Each cycle, oestrogen makes the endometrium thicken and proliferate (grow and divide). Progesterone normally counterbalances this growth, and the lining is shed when hormone levels fall.
When oestrogen acts without enough progesterone to balance it, we call it unopposed oestrogen. The glands of the lining keep growing, which can cause endometrial hyperplasia (overgrowth of the glands), and this usually comes before the cancer. Endometrial cancer is usually an adenocarcinoma (a cancer derived from glandular tissue), and the common type responds to oestrogen.
Anything that lengthens or strengthens oestrogen exposure without enough progesterone to oppose it raises the risk, including:
- obesity, because fat tissue makes oestrogen;
- anovulatory cycles (cycles in which no egg is released), so no progesterone is made;
- an early first period or a late menopause, which mean more years of oestrogen exposure;
- oestrogen-only hormone replacement therapy (HRT) in a woman with a uterus;
- tamoxifen used for more than 2 years: it blocks oestrogen in the breast but acts as a partial oestrogen agonist (it switches oestrogen receptors on, though less strongly than natural oestrogen) in the endometrium.
The same logic explains why women who still have a uterus are given a progestogen (a drug similar to progesterone) alongside the oestrogen in HRT: it normally provides the opposing effect that balances oestrogen. Bleeding after the menopause is the typical presentation and needs investigation, although many women with it turn out not to have cancer.
Key facts
- Mechanism
- unopposed oestrogen is oestrogen acting on the endometrium without enough progesterone to balance it.
- Comes before the cancer
- endometrial hyperplasia (overgrowth of the glands of the lining) usually comes before the cancer.
- Cell type
- endometrial cancer is usually an adenocarcinoma, a cancer derived from glandular tissue.
- Risk factors
- obesity, anovulatory cycles, an early first period, a late menopause, oestrogen-only HRT and tamoxifen.
- Protection
- continuous combined HRT, which includes a progestogen, carries a lower risk than oestrogen-only HRT.
- Presentation
- bleeding after the menopause is the typical presentation and needs investigation.
Exam traps
- Tamoxifen raises endometrial cancer risk not through rebound growth after blocking oestrogen receptors in the endometrium, but because it acts there as a partial oestrogen agonist and stimulates the lining.
- High progesterone exposure would reduce, not raise, the risk of endometrial cancer, because progesterone opposes oestrogen's growth signal; it is a low or absent progesterone effect that matters.
- Continuous combined HRT does not raise endometrial cancer risk in the way oestrogen-only HRT does, because it provides a progestogen every day to oppose oestrogen's effects on the endometrium.
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