Hormone replacement therapy (HRT) for women previously treated for endometrial cancer

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The issue
Endometrial cancer develops from the lining of the womb (uterus). It is the sixth most common cancer worldwide and mainly affects women around the time of or after the menopause (the final menstrual period). At an early stage, where the cancer has not spread outside of the womb, survival rates are excellent with a five-year survival of up to 97%. Treatment of endometrial cancer normally involves surgery to remove the womb, fallopian tubes (that connect the uterus to the ovaries) and ovaries (which produce eggs) (hysterectomy and bilateral salpingo-oophorectomy). This may cause the onset of menopausal symptoms in women diagnosed prior to the menopause, or women may already be suffering from menopausal symptoms when they are diagnosed.

Hormone replacement therapy (HRT) is used to treat menopausal symptoms such as hot flushes, night sweats and vaginal dryness. In younger menopausal women, HRT may also help to maintain bone strength and prevent osteoporosis (weak bones). However, the safety of HRT after endometrial cancer is not known. Some types of endometrial cancer cells may be stimulated to grow by oestrogen, which is the main hormone in some types of HRT. Therefore, HRT has the potential to increase the growth of endometrial cancer cells left behind after treatment (due to microscopic undetected spread outside of the womb, fallopian tubes and ovaries), so promoting tumour recurrence (regrowth). Some doctors may not prescribe HRT after a diagnosis of endometrial cancer due to this theoretical risk. However, most women treated for early-stage endometrial cancer will not have any residual cancer cells following surgery. Menopausal symptoms can severely affect quality of life and early menopause can affect long-term health. HRT could potentially improve quality of life and long-term health, and women treated for endometrial cancer need to be able to balance the risks and benefits of HRT to decide about their treatment.

The aim of the review
The aim of this systematic review was to determine the effectiveness (does it improve symptoms) and safety of HRT in women who have been treated for endometrial cancer. Safety of HRT in this situation included effects on survival and the specific risk of endometrial cancer regrowing.

What were the main findings?
We searched clinical trial databases to look for any evidence of effectiveness and safety of HRT use in women who had had endometrial cancer up to May 2017. We only found one study that randomly allocated women to receive either HRT or a placebo (pretend treatment). This found no difference in the likelihood of the cancer regrowth between the two groups. They showed that HRT may or may not increase the risk of recurrence of developing a new cancer. They did not provide any information on survival or symptom relief. However, the study was not completed due to poor recruitment into the clinical trial, so was not large enough to definitively say whether the use of HRT could be recommended after treatment for early endometrial cancer.

Quality of the evidence
We are uncertain whether HRT increases the risk of recurrence after a diagnosis of endometrial cancer, as the certainty of the current evidence was very low. We identified only one randomised trial and this trial did not include enough women to definitely answer the question. This trial also had areas of potential bias that reduced our certainty in the results.

What were the conclusions?
Limited, very-low certainty, evidence suggests that HRT may have little or no effect on the risk of endometrial cancer returning for women who have been treated surgically for an early-stage endometrial cancer. There were no data to say whether HRT had an effect on overall survival after hysterectomy for endometrial cancer.