Pregnancy reduces endometrial cancer risk regardless of duration
Pregnancy attenuates the risk of endometrial cancer regardless of whether it ends shortly after conception or at 40 weeks of gestation, a study has shown. A biological process occurring within the first weeks of pregnancy drives this risk reduction, as shown by pregnancies terminated through induced abortions having similar risk reductions as those ending in childbirth.
“Our study shows that the protective association between pregnancy and endometrial cancer is equivalent for pregnancies resulting in induced abortion and birth, and thus suggests that the association is attributable to a woman’s underlying fecundity or a biological process occurring early in gestation,” the researchers said.
Endometrial cancer developed in 6,742 out of 2,311,332 Danish women with 3,947,650 pregnancies during 57,347,622 person-years of follow-up.
After adjusting for age, period and socioeconomic factors, an association was found between a first pregnancy and a markedly reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk [aRR], 0.53, 95 percent CI, 0.45–0.64) or childbirth (aRR, 0.66, 0.61–0.72). Each subsequent pregnancy also resulted in further risk reduction, regardless of whether it ended in induced abortion (aRR, 0.81, 0.77–0.86) or childbirth (aRR, 0.86, 0.84–0.89). [BMJ 2019;366:l4693]
Results were unchanged even after considering the duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity and socioeconomic factors.
The protective benefit of pregnancy against endometrial cancer could be due to the fecundity effect, by which the number of pregnancies represented a woman’s ability to become pregnant, and thus her healthy endometrium and endocrine system, according to the researchers.
Another mechanism could be the early gestational effect, which could be explained by a rapid increase of the progesterone to oestrogen ratio in the first weeks after conception, when progesterone levels increase more than threefold and oestrogen levels increase only modestly, they added.
“The findings from our study and others support an early gestational process, as each additional pregnancy was associated with a reduction in risk of endometrial cancer, and because adjustment for infertility did not explain the effect of parity on risk,” the researchers said.
These findings, however, differed from the current understanding of the cause of endometrial cancer, which is focused on the unopposed oestrogens hypothesis, where the endometrial cancer risk intensifies with the number of menstrual years and eases with the years of pregnancy and oral contraceptive use. [Am J Epidemiol 1996;143:1195-1202; Epidemiology 2011;22:638-645; Br J Cancer 1988;57:205-212; J Natl Cancer Inst 1999;91:1131-1137; Acta Obstet Gynecol Scand 2018;97:1168-1177]
“However, a study found that each additional year of pregnancy was associated with a 22-percent reduction in risk of endometrial cancer, whereas both each additional year of oral contraceptive use and each year of delayed menarche or advanced menopause were associated with only around an 8-percent risk reduction, indicating that a pregnancy affects a woman’s risk of endometrial cancer through a different mechanism than number of menstrual years,” the researchers noted. [Int J Cancer 2010;127:442-451]
The present nationwide, register-based cohort study included all Danish women born from 1935 to 2002 to explore the relationship between pregnancy duration and risk of endometrial cancer. Log-linear Poisson regression was used to estimate RR (incidence rate ratio) for endometrial cancer by pregnancy number, type and duration.
“Future research is of great importance as it could lead to insights into early gestational factors that potentially could facilitate the prevention of endometrial cancer,” the researchers said.