The Essential Epidemiology of Cancer of the Endometrium: An Update
The central epidemiologic features of cancer of the endometrium are the following: a much increased risk associated with obesity, evident both in premenopausal and postmenopausal women; a decreased risk with increasing parity; a decreased risk with increasing duration of use of combination-type oral contraceptives (COCs); an increased risk with menopausal estrogen therapy (ET) use; and a marked reduction in this risk when a progestin is added to ET (estrogen–progestin therapy, EPT) and continuous-combined EPT may be associated with a decreased risk, especially in heavier women. These observations are readily explained by a simple “unopposed estrogen hypothesis”; that is, estrogen “unopposed” by a progestin increases risk. The basis for this hypothesis is that estrogen unopposed by a progestin increases cell division in the endometrium. Analysis shows that reducing the standard dose of ET by as much as a half will have no effect on the ET-associated risk of endometrial cancer. This hypothesis also provides an explanation of why 1 year of COC use has a smaller preventive effect than a birth. It also suggests that the recently introduced COCs with an increase in the number of days of active pill intake from 21 to 24 days per 28-day COC cycle will significantly increase the protective effect of COC use. Use of the progestin-containing intrauterine system (IUS) with its continuous release of progestin reduces the risk of endometrial cancer to a marked extent; a year of such use may provide as much protection as a birth. Some of this progestin-containing IUS effect may, however, not be due to the progestin as non-hormonal IU devices (IUDs) have also been shown to decrease endometrial cancer risk although to a lesser extent. It is now clear that the protective effect of parity is markedly affected by the age at which the last birth occurs: for the same number of total births, there is a 45 % greater effect of a last birth after age 40 than a last birth before age 25. It remains to be seen if this age effect is also seen with the protection afforded by hormonal IUSs or with COCs where the active pills are given for 12 weeks out of every 13.
KeywordsEndometrial cancer Births Body mass index Weight Estrogen Estrogen therapy
Research reported in this publication was partially supported by NCI under award number P30CA008748 (PI: Thompson) to Memorial Sloan Kettering Cancer Center.
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