Table 1.

Risk factors for endometrial cancer in relation to the estrogen/progestogen imbalance hypothesis and the proposed inflammation hypothesis

Risk/protective factorProposed mechanism—estrogen/progestogen imbalance hypothesis*Proposed mechanism—inflammation hypothesis
Risk factors
    Unopposed estrogen therapy useUnopposed estrogen exposure in the endometriumIncreased exposure to estrogens increases inflammatory response in the endometrium
    ObesityIncreased systemic exposure to unopposed estrogens via aromatization of androgens in adipose tissue and via decreased sex hormone–binding globulin productionIncreased proinflammatory systemic milieu
Decreased progesterone exposure leading to unopposed estrogen exposure due to anovulation
    Diabetes mellitus?Increased proinflammatory systemic milieu
    Polycystic ovary syndromeIncreased systemic exposure to unopposed estrogens via aromatization of androgensIncreased proinflammatory systemic milieu
    Early menarche/late menopauseIncreased lifetime exposure to estrogen in the endometriumIncreased lifetime exposure to inflammation via increased number of menstruations
    AnovulationDecreased progesterone production leading to unopposed estrogen exposure in the endometriumDecreased exposure to progesterone increases inflammatory response in endometrium
    Menorrhagia?Increased exposure to inflammation via menstruation
Protective factors
    PregnancyIncreased exposure to progesteroneDecreases exposure to menstruation
Increased exposure to anti-inflammatory effect of progesterone
Decreased inflammatory milieu in the uterus
    SmokingDecreased exposure to estrogens due to increased metabolic clearance and production of less estrogenic metabolitesProduction of anti-inflammatory estrogen metabolite
    Oral contraceptive useIncreased exposure to progestinsIncreased exposure to anti-inflammatory progestins
Decreased exposure to menstruation