Tamoxifen: partial agonist in endometrium and bone
Tamoxifen, a drug that binds the oestrogen receptor, blocks it in breast tissue but partly switches it on in bone and in the endometrium (the lining of the womb).
Remember
In breast tissue tamoxifen blocks the oestrogen receptor, but in the endometrium and bone it partly activates it, which explains the risk of endometrial hyperplasia and cancer, so abnormal vaginal bleeding on tamoxifen should be reported and assessed.
Memory aid
with tamoxifen, breast off, womb and bone partly on
Use it as a quick picture of where tamoxifen blocks the oestrogen receptor and where it only partly switches it on.
Tamoxifen is a selective oestrogen receptor modulator (SERM), meaning it binds the oestrogen receptor but has different effects in different tissues. In the breast it is an antagonist, so it blocks the receptor. That is what makes it useful against oestrogen-receptor-positive breast cancer (cancer whose cells rely on oestrogen to grow).
In the endometrium and in bone it is a partial agonist: it switches the receptor on only partly, in an oestrogen-like way. In bone this can help to maintain bone mineral density (the amount of mineral that keeps bone strong) after menopause. In the endometrium it stimulates growth, which is linked with endometrial hyperplasia (overgrowth of the lining) and a higher risk of endometrial cancer.
The tissues differ because the receptor takes up a different shape according to the drug bound to it, and the helper proteins in each tissue help to decide whether it is switched on.
Because tamoxifen stimulates the endometrium, a woman taking it should report any abnormal vaginal bleeding so that it can be assessed for hyperplasia or cancer. Raloxifene, a related SERM, differs here: it is an antagonist in the endometrium as well as in the breast, so it does not carry this risk.
Key facts
- Breast
- tamoxifen is an antagonist here, which is why it is used in oestrogen-receptor-positive breast cancer.
- Endometrium
- tamoxifen is an agonist here, so the risk of endometrial hyperplasia and cancer is higher.
- Bone
- tamoxifen is a partial agonist here, which can help to maintain bone mineral density after menopause.
- Raloxifene contrast
- raloxifene, a related SERM, is an antagonist in the breast and the endometrium and an agonist in bone.
- Adjuvant treatment
- given after surgery to lower the chance of recurrence, it typically runs for 5 to 10 years, which gives the endometrium a long exposure to this stimulation.
- Blood clots
- tamoxifen also adds to the risk of venous thromboembolism (blood clots in the veins).
- Bleeding
- a woman on tamoxifen who has vaginal bleeding should report it so that the cause can be assessed.
Exam traps
- A pure antagonist, which would block the oestrogen receptor everywhere, does not describe tamoxifen, because tamoxifen has partial oestrogenic effects in other tissues and is associated with endometrial hyperplasia and cancer.
- Tamoxifen does not block progesterone receptors in the uterus, because it acts on oestrogen receptors, and the oestrogen-like stimulation of the endometrium is what explains the bleeding warning.
- Tamoxifen is not an antagonist in the endometrium, because there it is an agonist that stimulates the lining to grow instead of thinning it.
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