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Endometrial Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Overview

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Magnitude of Effect: The risk of endometrial cancer associated with unopposed estrogen use for 5 or more years is more than tenfold higher than nonhormone use. Addition of progesterone to estrogen negates this risk, but combined HT increases the risk of breast cancer, which is not observed with unopposed estrogen.

Study Design: Randomized controlled trials, cohort, and case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Harms

Based on solid evidence, the combined use of estrogen and progestin are associated with an increased risk of breast cancer, heart disease, stroke, and thrombosis.[11,13,14] Based on solid evidence, unopposed estrogen is associated with an excess risk of stroke and thrombosis.[15]

Magnitude of Effect: Combined estrogen and progestin after a mean of 5 years of treatment: Approximately a 26% relative increase in incidence of invasive breast cancer; a 29% relative increase in cardiovascular heart disease; a 41% relative increase in stroke, associated with combined estrogen and progestin; and a 113% relative increase in pulmonary embolus.

Estrogen only after a mean follow-up of 6.8 years: Approximately a 39% relative increase in stroke and a 34% relative increase in pulmonary embolus. Risk of cardiovascular heart disease and breast cancer were nonstatistically significantly lower in the estrogen-treated group.

Study Design: Randomized placebo-controlled trials.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Selective estrogen receptor modifiers

Based on solid evidence, more than 2 years of tamoxifen use is associated with an increased risk of endometrial cancer.[16,17] A different selective estrogen receptor modifier, raloxifene, does not have this association.[18,19]

Magnitude of Effect: Women taking tamoxifen for more than 2 years have a 2.3-fold to 7.5-fold relative risk (RR) of endometrial cancer.

Study Design: Multiple randomized controlled trials.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Obesity

Based on solid evidence, being overweight or obese is associated with an increased risk of endometrial cancer.[20,21,22]

The risk of endometrial cancer increases 1.59-fold per 5 kg/m2 change in body mass.[23]

Study Design: Multiple randomized controlled trials.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.
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