Primary prevention

Most cases of endometrial cancer cannot be prevented. However, risk can be reduced by addressing risk factors, such as obesity and overweight. Use of combined oral contraceptives is associated with reduced risk of endometrial cancer; use of levonorgestrel-releasing intrauterine devices may have a risk-reducing effect.[81][94][95]​​​​ Additional risk-reduction strategies should be discussed with women with Lynch syndrome.​

Women with Lynch syndrome

Given the high rate of endometrial cancer in women with Lynch syndrome (lifetime risk 35% to 54% for the MLH1 variant; 21% to 57% for MSH2 and EPCAM; 16% to 49% for MSH6; 13% to 26% for PMS2) compared with the general population (3.1%), these patients may benefit from a prophylactic, risk-reducing hysterectomy after completion of childbearing.[81][82]​​​​​[96][97]​​​​​​ ​​Prophylactic bilateral salpingo-oophorectomy (BSO) may also be beneficial because of the high risk of ovarian cancer associated with some Lynch syndrome mutations.[81]​​[82]​​[98]

Prophylactic hysterectomy and BSO have been reported to prevent 100% of endometrial and ovarian cancer in women undergoing risk-reducing surgery for Lynch syndrome.[98]

The decision to undergo risk-reducing surgery and its timing should be individualised (e.g., based on age, whether childbearing has been completed, menopausal status, comorbidities, specific gene mutation, and family history).[81]​ Consideration of risk-reducing surgery may start at age 40 years for women with MSH1, MSH2/EPCAM, or MSH6 variants, and age 50 years for those with PMS2 variants.[81]​ Timely discussion of risk-reducing surgery is recommended.

Non-surgical risk reduction

If risk-reducing surgery is declined or not possible, alternative risk-reduction strategies (including education about symptoms associated with endometrial cancer and/or surveillance) should be discussed.[81]​ Use of oral contraceptives or levonorgestrel-releasing intrauterine devices may be considered as risk-reduction agents for endometrial and ovarian cancers in women with Lynch sydrome. However, evidence in this population is limited.[81][82][99]​​​

Aspirin is recommended to reduce the risk of colorectal cancer, but an appreciable effect for endometrial cancer has not been consistently demonstrated.[100]​​[101]

Secondary prevention

Oestrogen replacement therapy in women who have post-menopausal symptoms and who have been diagnosed and treated for endometrial cancer remains controversial.[272][273] There is a theoretical risk that oestrogen may increase the incidence of recurrence, because the most common type of endometrial cancer is oestrogen-driven. However, limited and low-certainty evidence suggests that hormone replacement therapy (HRT) may have little or no effect on the risk of endometrial cancer recurrence among women treated surgically for an early-stage endometrial cancer.[265][266] Therefore, women with early-stage disease (low-recurrence risk) who wish to use HRT may do so after detailed discussion with their clinician.[266]

Women with higher risk of recurrence or advanced disease should probably avoid oestrogen-containing products as a preventative measure.[266]

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